Soft tissue/Bone Flashcards

Question

Bone island/enostosis.

Answer 1

The terms bone island and enostosis may be used interchangeably to describe the same lesion, namely, a localized area of compact bone within the medullary cavity of a bone. The area may be encompassed by the medullary cavity or show focal attachment to the inner cortex of the host bone. Bone islands are characteristically asymptomatic and discovered incidentally. They are most common in the pelvis, proximal femora, and ribs. Over time, some may decrease in size and disappear, while others may grow. Rare cases may exceed 2 cm (giant bone island). Rarely, multiple bone islands are noted, a condition known as osteopoikilosis. In the rare case of a biopsied bone island, the histology shows compact lamellar bone with prominent Haversian canals. Thickened trabeculae of lamellar bone, when radiating from the periphery of the lesion, usually blend with the bone trabeculae of the host bone.

Answer 2

Osteochondromas are the most-common bone lesions (30-50% of benign resected lesions). 85% are solitary and sporadic. The 15% of osteochondromas with multiple lesions is indicative of a condition transmitted with a dominant pattern of inheritance known as hereditary osteochondromatosis. Both solitary and multiple forms have no sex predilection. Osteochondromas may occur in any bone formed by enchondral ossification. The most common sites, in decreasing order of frequency, are the metaphyses of the distal femur, the upper humerus, the upper tibia, and the fibula. Grossly, osteochondromas are sessile or pedunculated bony projections covered by a smooth, rounded to bosselated, cartilagenous cap of uniform thickness, usually a few millimeters thick. The base is continuous with the neighboring bone marrow. The cartilage cap is invested by perichondrium and composed of hyaline-type cartilage with clustered chondrocytes embedded in an abundant matrix. Its deepest portion is identical to growth plate cartilage and is arranged in columns that undergo enchondral ossification.

Answer 3

Chondrosarcoma may arise in osteochondroma, more commonly in patients with multiple osteochondromas. Malignant transformation is frequently associated with clinical symptoms, such as pain, neurologic symptoms, and growth of a previously stable lesion. The mean age of patients with malignant transformation of an osteochondroma is 35 years (1 to 2 decades younger than patients with primary chondrosarcoma). Radiographically, sarcomatous transformation is suspected if there is an increase in size after growth plate closure, or surface irregularities with inhomogeneous mineralization. The most common sites for malignant transformation are the pelvic bones and proximal and distal femur for solitary lesions. In patients with multiple osteochondromas, the pelvic bones, scapula, and thoracic spine are the most common sites, particularly if they have been directly or indirectly included in radiation ports, especially during active skeletal growth. Malignancy is usually associated with soft tissue infiltration, most often by nodules separated from the main tumor mass, by bone stalk permeation, by host lamellar bone entrapment, by markedly increased cellularity with atypia, and by mitotic activity, myxoid stromal changes, and tumor necrosis. The prognosis of chondrosarcoma ex-osteochondroma is generally excellent, provided complete resection is possible.

Answer 4

Chest wall hamartoma is a nonneoplastic, congenital lesion that affects the chest wall of infants. In ~40% of cases, it is present at birth or diagnosed in utero. Although generally intrathoracic, a hamartoma may protrude into the chest wall soft tissue. Hamartomas originate from the posterior or lateral aspect of a rib, and multiple ribs may be involved. The most commom symptom is respiratory distress. On radiographs, a chest wall hamartoma appears as a mineralized mass that, if expansive, may partially destroy neighboring ribs. Gross specimens usually appear as circumscribed lesions composed of tan-white soft tissue, surrounding large, cystic, blood-filled spaces. Microscopically, the solid areas consist of fibrous tissue containing mature hyaline cartilage with variable enchondral ossification and areas resembling aneurysmal bone cyst. Symptomatic lesions may require resection. Others may be followed and tend to regress.

Answer 5

Foreign body giant cells, Langhans giant cells, and Touton giant cells. All three types are transformed macrophages; mononuclear phagocytes fused under the influence of cytokines. Foreign body giant cells have nuclei that are randomly distributed but often aggregate as centrally located, overlapping nuclei. Langhans giant cells have a peripheral ring-like arrangement of nuclei in an arcuate configuration but no rim of clear cytoplasm. Touton giant cells have a ring of nuclei separating a peripheral clear or foamy rim of cytoplasm from central, more eosinophilic cytoplasm. The peripheral cytoplasm appears clear due to high lipid content. Touton giant cells are seen in lesions with high lipid content, such as xanthomas, xanthogranulomas, and fat necrosis. Touton giant cells can also be seen in dermatofibroma. Other types of multinucleated giant cells include epithelium-derived MGCs, which can be prominent in certain viral infections such as measles (Warthin-Finkeldey cells), RSV, HSV/VZV, and parainfluenza. Also, MCGs derived from neoplastic cells may be formed in a variety of neoplasms.

Answer 6

Fibromatosis: Painless, slow-growing, non-circumscribed. 60% have lymphoid aggregates at the periphery. Spindle cells forming interlacing fascicles with variable collagen deposition and cellularity. No/rare mitotic figures. Nodular fasciitis: Painful, fast-growing, circumscribed. Ropy keloid-type collagen, micro-hemorrhages/RBC extravasation. Zonation effect with hypocellular central region and hypercellular periphery. Often frequent mitotic figures (but no atypical forms).

Answer 7

Hyalinizing spindle cell tumor with giant rosettes is now regarded as a variant of low grade fibromyxoid sarcoma. Hyalinizing spindle cell tumor with giant rosettes is also called low grade fibromyxoid sarcoma with giant collagen rosettes.

Answer 8

96% of low grade fibromyxoid sarcomas show a characteristic balanced translocation involving the FUS gene on chromosome 7 and the CREB3L2 gene on chromosome 16.

Answer 9

Unlike LGFMS which occurs in the deep soft tissues of young adults, myxofibrosarcoma typically occurs in the subcutaneous tissues of elderly patients. Histologically, myxofibrosarcoma is uniformly myxoid and lacks the alternating fibrous areas seen in LGFMS. Furthermore, myxofibrosarcoma invariably shows a greater degree of cytologic atypia and nuclear pleomorphism.

Answer 10

PAS stain shows intracytoplasmic glycogen and PAS positive diastase resistant rhomboid crystals, a characteristic feature of ASPS. Nuclear expression of TFE3 is usually present. Muscle markers are expressed in less than half of cases. Cytokeratin, EMA, GFAP, and synaptophysin are negative. S100 is occasionally positive.

Answer 11

Tenosynovial giant cell tumors (TSGCT) are a group of generally benign intra-articular and soft tissue tumors with common histologic features. They can be roughly divided into localized and diffuse types. Localized types include giant cell tumors of tendon sheath (localized TSGCT) and localized pigmented villonodular synovitis (intra-articular, localized TSGCT), whereas diffuse types encompass conventional pigmented villonodular synovitis (intra-articular, diffuse-type giant cell tumor) and diffuse type giant cell tumor (extra-articular, diffuse TSGCT). Malignant TSGCT/malignant PVNS is rare. Localized tumors are generally indolent, whereas diffuse tumors are locally aggressive. Recent developments indicate that tenosynovial giant cell tumors are clonal neoplastic tumors driven by overexpression of CSF1 (macrophage Colony Stimulating Factor 1). Most giant cell tumors of tendon sheath (localized TSGCT) occur in the digits, especially the fingers, and usually on volar surfaces. Localized pigmented villonodular synovitis (intra-articular, localized TSGCT) is morphologically identical to GCTTS. The knee is the most common location. The most common location for conventional pigmented villonodular synovitis (intra-articular, diffuse-type giant cell tumor) is the knee. Diffuse type giant cell tumor (extra-articular, diffuse TSGCT) is defined by invasive, extra-articular disease, regardless of whether the GCT arose from a joint or soft tissue.

Answer 12

Tenosynovial giant cell tumors (TSGCT) are a group of generally benign intra-articular and soft tissue tumors with common histologic features. They can be roughly divided into localized and diffuse types. Localized types include giant cell tumors of tendon sheath (localized TSGCT) and localized pigmented villonodular synovitis (intra-articular, localized TSGCT), whereas diffuse types encompass conventional pigmented villonodular synovitis (intra-articular, diffuse-type giant cell tumor) and diffuse type giant cell tumor (extra-articular, diffuse TSGCT).TSGCTs have a polymorphous cell population comprising large histiocytoid cells with abundant eosinophilic cytoplasm and eccentric vesicular nuclei, smaller mononuclear stromal cells with oval or reniform nuclei, osteoclast-like giant cells, and xanthoma cells. Mitotic figures can sometimes be very abundant. Large hemosiderin deposits, zones of fibrosis including areas resembling osteoid, sheets of xanthoma cells, and dyshesive cellular areas forming a pseudoalveolar pattern are common findings. Conventional pigmented villonodular synovitis (intra-articular, diffuse-type giant cell tumor) will have additional features: unencapsulated, pronounced villonodular architecture, often contains elongated synovial-line spaces, erosion into underlying cortex and articular cartilage. Diffuse type giant cell tumor (extra-articular, diffuse TSGCT) is defined by invasive, extra-articular disease, regardless of whether the GCT arose from a joint or soft tissue. It widely infiltrates and entraps adjacent soft tissue and frequently erodes bone. Pseudoalveolar spaces and cellular areas devoid of giant cells are often present.

Answer 13

Denervation and type-2 fiber atrophy. Group atrophy of AAF is an important feature that distinguishes denervation atrophy from type-2 fiber atrophy.

Answer 14

Adenosine triphosphate stains are used for distinguishing type-1 (slow, oxidative) and type-2 (fast, glycolytic) fibers. These are stains for enzyme activity, which require frozen sections, and can be technically difficult to perform. With the stain for myosin ATPase at pH ~10.5, type 2 myofibers are stained brown, and type 1 fibers are stained pink with an eosin counterstain to make them visible. The same stain, performed at a pH of ~4.3, would demonstrate staining of the type 1 myofibers, such that the section would show exactly the reverse pattern. Staining of normal muscle shows a random, almost checkerboard distribution of the 2 types of myofibers. However, IHC stains for slow myosin found in type-1 fibers and fast myosin found in type-2 fibers is available. Also, the IHC stains are permanent, but the myosin ATPase stain fades after a few months.

Answer 15

This is usually an incidental asymptomatic tracheal and bronchial multinodular growth arising from the cartilaginous components of the airway. Its distribution along the cartilaginous surfaces of the airway is radiographically and bronchoscopically distinct, sparing the membranous surface of the trachea. Cases that involve the bronchus can cause obstruction necessitating resection. The nodules are composed of cartilage and ossification, with or without adipose tissue. Bone marrow elements can also be seen.

Answer 16

A benign Triton tumor is a neuromuscular hamartoma/choristoma. It is a rare developmental lesion of mature skeletal muscle and nerve. Microscopically, is made up of multiple nodules, each 3-5 mm, separated by narrow bands of connective tissue. Nodules are composed of fasicles of striated muscle of varying size with nerve fibers (myelinated or not) within same perimysial fibrous sheath. Stroma may be more cellular with bland spindle cells and resemble fibromatosis. A malignant Triton tumor is made up of both malignant schwannoma cells and malignant rhabdomyoblasts, and is classified as a MPNST with rhabdomyosarcomatous differentiation. The name "triton" was first used in reference to observation of supernumerary limbs containing bone and muscle growing the backs of tritons (a name given to some species of sea snails) after the implantation of the sciatic nerve into the soft tissues of the back.

Answer 17

Fibrous dysplasia is a benign fibro-osseous lesions, which may present in either monostotic or polyostotic forms. The monostotic form occurs most frequently and represents ~75% of FD cases. This form occurs, in decreasing order of frequency, in the craniofacial bones, ribs, femurs, tibias, and humeri. The monostotic form of FD may present with pain or a pathologic fracture, usually in patients aged 10 to 30 years. The degree of bone deformity is relatively less severe compared with that of the polyostotic type.

Answer 18

A small subset of cases of the polyostotic form of fibrous dysplasia (~3%) occurs along with endocrine abnormalities and coast of Maine cafe-au-lait spots, a triad called McCune-Albright syndrome.

Answer 19

Molecular findings in FD, and especially those for MAS, suggest it is caused by a somatic mutation early in embryonic life that causes a gene mosaicism. The earlier the mutation occurs, the more widespread the effects will be. The gene is located on 20q13, an area that codes for the alpha subunit on G-protein receptors. This mutation is also present in various endocrine tumors as well as FD. The G-proteins begin a cascade that ultimately leads to activation of the enzyme adenylyl cyclase that produces cAMP. In MAS, there is a missense mutation that causes the substitution of arginine in position 201 of the Gs-alpha gene. Normally, there is an almost immediate deactivation of adenylyl cyclase and a breakdown of the cAMP. In MAS, that does not occur. Overproduction of cAMP leads to increased amounts of activity that affect each tissue differently based on its designated function.

Answer 20

FD has a classic histology of low to moderately cellular fibrous stroma surrounding irregular, curvilinear trabeculae of woven bone, which is arranged in a pattern commonly referred to as "Chinese letters." The stroma may be variably collagenized, and the ratio of fibrous tissue to bone can range from being totally fibrous to being densely packed with dysplastic trabeculae. The trabeculae may even contain transverse lines mimicking Paget disease. A key feature is the conspicuous absence of osteoblastic rimming. Secondary changes, such as a metaplstic chondroid component or aneurysmal bone cyst-like changes, can include cystic degeneration with xanthomatous histiocytes and/or giant cells and myxoid change. IHC serves no purpose in the diagnosis of FD other than to rule out the possibility of a malignant lesion with a pertinent history.

Answer 21

The histologic differential diagnosis is similar to the radiographic differential diagnosis, including osteofibrous dysplasia, fracture callus, nonossifying fibroma, and low-grade osteosarcoma. Low-grade chondrosarcoma may be part of the differential diagnosis if there is a prominent chondroid component. Osteofibrous dysplasia and fracture callus can be difficult to differentiate, but the history and location should help, and they typically have prominent osteoblastic rimming around the bone trabeculae. Fracture callus should have a history of trauma, and osteofibrous dysplasia occurs almost exclusively in the tibia and fibula. Nonossifying fibroma resembles benign fibrous histiocytoma with a storiform arrangement of the spindle cells and occasional multinucleated giant cells. However, bone-matrix formation is absent. Particularly when the mandible is involved, ossifying fibroma must be considered in the differential diagnosis.

Answer 22

1% of cases of fibrous dysplasia undergo malignant transformation. The frequency of malignant change is increased with the polyostotic form of FD, especially in patients with McCune-Albright syndrome, Mazabraud syndrome, or prior radiation exposure. Osteosarcoma (~70%), fibrosarcoma (~20%), chondrosarcoma (~10%), malignant fibrous histiocytoma (~4%). Once FD is diagnosed, routine follow-up should be done on a yearly basis with x-ray examination.

Answer 23

Kaposi sarcoma (KS) is a low-grade vascular tumor associated with Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) infection. Kaposi sarcoma lesions predominantly present at mucocutaneous sites, but may involve all organs and anatomic locations. Recognized epidemiologic-clinical forms of KS include classic, African (endemic), AIDS-associated (epidemic), and iatrogenic KS. New clinical manifestations have been described, such as antiretroviral therapy–related KS regression or flares. Kaposi sarcoma lesions evolve from early (patch stage) macules into plaques (plaque stage) that grow into larger nodules (tumor stage). Newer histologic variants include anaplastic, hyperkeratotic, lymphangioma-like, bullous, telangiectatic, ecchymotic, keloidal, pyogenic granuloma–like, micronodular, intravascular, glomeruloid and pigmented KS, as well as KS with sarcoidlike granulomas and KS with myoid nodules. Latency-associated nuclear antigen (HHV8) is the most specific immunohistochemical marker available to help distinguish KS from its mimics. KS remains one of the most common AIDS-defining malignancies.

Answer 24

With the advent of genomic technologies, proliferating KS spindle tumor cells are now known to be of endothelial origin, confirming former studies that used histochemistry and ultrastructural findings. Circulating blood mononuclear and endothelial “progenitor cells” are believed to be the source of early KS lesions. Infection with HHV8 reprograms the host's blood endothelial cells so that they resemble lymphatic endothelium, upregulating several lymphatic-associated genes such as lymphatic vessel endothelial receptor 1 (LYVE1), podoplanin, and vascular endothelial growth factor receptor 3 (VEGFR3). However, HHV8 infection alone appears to be insufficient for the development of KS. Kaposi sarcoma progression relies also on some degree of host immune dysfunction and the local inflammatory milieu. Kaposi sarcoma growth involves the upregulation of many key HHV8 gene products, such as the latency-associated nuclear antigen (LANA-1 or LNA-1). Like other herpesviruses, HHV8 remains latent within cells and has developed a variety of mechanisms to evade the host immune system.

Answer 25

Classical type: Mainly males aged 40-70 years, of Mediterranean or Jewish Ashkenazi origin. Skin of the lower extremities, but mucosal and visceral lesions may develop. Indolent. African type: Middle-aged black adults and children from equatorial Africa. Multiple localized skin tumors, involving lower extremities and/or lymph nodes. Progressive; lymphadenopathic form is aggressive. AIDS-associated type: Mainly homosexual males and IVDUs aged 20-50 years; now equally affects women and children in Africa. Disseminated mucocutaneous and visceral involvement. Aggressive; lesions may regress or flare with initiation of antiretroviral therapy. Iatrogenic type: Immunosuppressed persons of any age from autoimmune disease, drugs, or transplantation. Localized mucocutaneous or disseminated KS, with possible visceral lesions. Variable; may regress after immunosuppression is discontinued.

Answer 26

Early patch-stage KS is characterized by abnormal vessels lined by thin endothelial cells dissecting the dermis. Ramifying proliferating vessels often surround larger ectatic vessels and skin adnexa, producing the so-called promontory sign. This sign is not pathognomonic for KS, as it has also been described in other vascular lesions including benign vascular tumors and angiosarcoma. Sparse chronic inflammatory cells, extravasated red blood cells, and hemosiderin-laden macrophages are frequently present in patch KS lesions. These early histologic changes may be inconspicuous, and for that reason can be easily missed on biopsy. Plaque-stage KS lesions are characterized by a proliferation of both spindle cells and vessels, which in the skin involve most of the dermis, and sometimes even the subcutis. Well-developed KS tumors consist of several fascicles of these spindle-shaped tumor cells, often admixed with a variable chronic inflammatory infiltrate composed of lymphocytes, plasma cells, and dendritic cells. Kaposi sarcoma lesions also contain several hemosiderin-laden macrophages. Iron staining may help distinguish KS from similar-appearing interstitial granuloma annulare lesions that lack iron. In cross section, KS nodules display a sievelike appearance caused by the transection of spindle cells with intervening slitlike spaces. Eosinophilic and PAS–positive hyaline globules are a common finding in advanced KS lesions. These globules may be located within lesional cells or extracellularly. Typical KS lesions are devoid of marked cellular pleomorphism, necrosis, or a significant number of mitotic figures. In rare instances, AIDS-KS lesions may harbor concomitant pathologic findings, usually an opportunistic pathogen (eg, cryptococcosis, mycobacterial granulomas, or molluscum contagiosum).

Answer 27

These are at the two opposite ends of the spectrum of Kaposi sarcoma. Pre-KS lesions are also referred to as an "in situ" form of KS. These pre-KS lesions are characterized by groups of abnormal capillary-like vessels admixed with an inflammatory infiltrate, similar to patch-stage KS lesions. They are associated with lymphangiogenesis arising in the setting of chronic lymphedema. On the other end of the spectrum is anaplastic KS, sometimes referred to as pleomorphic KS. Anaplastic KS is an infiltrative, solid proliferation of spindle cells without vascular spaces, seen mainly in AIDS involving acral sites. This aggressive variant displays a greater degree of cellular and nuclear atypia, high mitotic index (eg, 5 to 20 mitoses per 10 high-power fields), and occasional necrosis.

Answer 28

Kaposi sarcoma lesional cells stain positively with the endothelial markers factor VIII–related antigen, CD31 (PECAM-1), and CD34. CD34 tends to show stronger expression than CD31 in advanced-stage lesions of KS. KS spindle cells also express several lymphatic specific markers such as D2-40 (which binds to the podoplanin antigen), LYVE-1 (a homologue of the CD44 glycoprotein receptor for hyaluronan), VEGFR-3 (the receptor for vascular endothelial growth factor C), and Prox-1. Bcl-2 also shows positivity in KS, related to the tumor's mechanisms of resisting apoptosis. The identification and localization of HHV8 within KS lesional cells by using LNA-1 (also called LANA-1) is the most diagnostically helpful immunostaining technique available to differentiate KS from its mimics. LNA-1 immunoreactivity in KS cells appears as stippled nuclear staining. However, HHV8 is not entirely limited to KS and has been detected in some angiosarcomas, hemangiomas, and dermatofibromas. LNA-1 IHC is favored over PCR detection of HHV8 in the evaluation of problematic vascular proliferations because contaminating mononuclear inflammatory cells may also harbor this herpesvirus, especially in HIV-positive patients.

Answer 29

Clinical history, such as HIV infection or status post transplant, may strongly support the diagnosis of KS. The differential diagnosis of patch-stage KS includes targetoid hemosiderotic hemangioma, fibrous histiocytoma, and interstitial granuloma annulare. The differential diagnosis of plaque-stage KS includes tufted angioma, targetoid hemosiderotic hemangioma, microvenular hemangioma, and acroangiodermatitis (“pseudo-Kaposi sarcoma”). The differential diagnosis of nodular KS includes bacillary angiomatosis, other vascular tumors (eg, spindle cell hemangioma and Kaposiform hemangioendothelioma), fibrohistiocytic tumors (eg, cellular, angiomatoid, and atypical variants of fibrous histiocytoma, and dermatofibrosarcoma protuberans), resolving dermal fasciitis, spindle cell melanoma, and several other spindle cell mesenchymal neoplasms (eg, cutaneous leiomyosarcoma).

Answer 30

Nerve sheath myxomas are rare, distinct tumors of the peripheral nerve sheath, with a peak incidence in the 30's. Patients present with solitary, superficial, multinodular, painless masses up to 2.5 cm, usually in the extremities. Tumors are typically slow growing, and often were present for years before being resected. They typically involve the dermis or subcutis, forming multinodular, avascular masses with abundant myxoid matrix and a peripheral fibrous border. Epithelioid Schwann cells are present in corded, nested, or syncytial-like aggregates. Stellate Schwann cells with cytoplasmic-nuclear invaginations are also present. The Schwann cells are strongly immunoreactive for S100 protein, GFAP, NSE and CD57. Occasional EMA+ perineurial cells are usually present, primarily in fibrous tissue. There are few/no mitotic figures. The differential diagnosis includes low grade fibromyxoid sarcoma of soft tissue, which typically has MFH-like areas, curvilinear vessels (thick walled with a broad arc) with condensation of cells around the vessels, and often non-specific cytogenetic aberrations. Neurothekeomas may have a myxoid stroma, but are distinct lesions by differential gene expression profiles and immunohistochemistry, and thought to be a variant of fibrous histiocytoma.

Answer 31

Epithelioid, spindle cell, retiform, kaposiform.

Answer 32

Synovial sarcoma is a spindle cell tumor arising in soft tissue which displays variable epithelial differentiation including glandular formation. It also has a specific genetic alteration, a chromosomal translocation t(X;18), that results in a fusion between the SS18 (SYT) gene on chromosome 18 and one of the SSX genes on the X chromosome, creating SS18-SSX1, SS18-SSX2, or SS18-SSX4 chimeric genes.

Answer 33

In the WHO classification there are two major categories of synovial sarcoma: the monophasic and the biphasic subtypes. The biphasic variant usually carries the SS18-SSX1 translocation, while the monophasic variant can have either fusion (SS18-SSX1 or SS18-SSX2). Monophasic SS typically demonstrates densely cellular sheets or vague fascicles of uniform, relatively small, ovoid neoplastic cells, with occasional nuclear palisading. Many tumors show s prominent hemangiopericytic growth pattern with staghorn-like vasculature arrangements, at least focally. Sometimes an extensive sampling can reveal a glandular epithelial component. Stromal collagen is generally scant. Myxoid change is usually focal with alternating areas of hypercellularity and hypocellular areas with microcyst formation. Mast cells may be abundant in this component.

Answer 34

The histologic appearance of monophasic synovial sarcoma can simulate that of several other soft tissue neoplasms including fibrosarcoma, leiomyosarcoma, MPNST, and SFT.

Answer 35

TLE1 is one of four transducin-like enhancer of split (TLE) genes that encode human transcriptional repressors. It is an important protein in the Wnt/Beta-catenin pathway, a signaling pathway that is strongly associated with SS. Strong nuclear TLE1 expression is a robust IHC biomarker for SS, particularly in those cases that do not exhibit biphasic histology, and helps distinguish this tumor from other spindle cell tumors. In an appropriate clinical background and morphology, strong nuclear TLE1 expression in a CD34-negative spindle cell tumor containing scattered CK-positive cells can be regarded as diagnostic of SS.

Answer 36

Enchondroma can have a similar microscopic appearance to well-differentiated chondrosarcoma, demonstrating a lobular architecture, cells with hyperchromatic nuclei, and multinucleation. In the hands and feet, an enchondroma can be hypercellular and have cellular atypia, features considered malignant when present at other sites. One useful morphologic distinction is the separation of cartilaginous lobules by hematopoietic marrow in enchondroma, different from the fibrous septa that separate the lobules in chondrosarcoma. Also, enchondromas do not permeate trabecular bone. Lastly, chondrosarcomas often have >10% myxoid degenerative changes and mitotic figures while enchondromas have neither. In cases lacking clear characteristic features, distinguishing enchondroma from well-differentiated chondrosarcoma may not always be possible. It should be kept in mind that acral enchondromas are far more common than chondrosarcomas.

Answer 37

During the initial reactive phase, occuring during the first few days, hemorrhage and a proliferation of small spindle cells are generated within the fracture. After about one week, proliferation is so intense that spindle cells can form a malignant-appearing, sarcoma-like, mitotically active mass intermixed with capillaries; atypical mitoses are absent. Typically, over the next two to four weeks, periosteal cells proximal to the fracture gap transform first into chondroblasts and then hyaline cartilage, while cells distal to the gap become bone forming osteoblasts, the former producing specialized collagen matrix and the latter osteoid. The two populations fuse forming a temporary fracture callus which is eventually replaced by first woven and then, by way of endochondral ossification, lamellar bone. The entire process in healthy individuals takes upwards of 6-8 weeks. Although early fracture callus formation can histologically resemble a malignant process, the radiographic features of a fracture callus do not. Thus, close clinical/radiologic/pathologic correlation is critical.

Answer 38

MPNSTs arise from peripheral nerves or show differentiation along the lines of nerve sheath elements (Schwann cells, perineural cells, fibroblasts). MPNSTs account for 5-10% of all soft tissue sarcomas, and one-fourth to one-half of them occur in patients with NF-1. Most lesions present as enlarging masses with or without associated pain and arise in association with major nerve trunks including the brachial plexus, sacral plexus and the sciatic nerve.

Answer 39

IHC stains for S100, CD57, myelin basic protein, and p53 are usually positive. Staining for S100 should be focally positive, but if strong, diffuse staining is present, a diagnosis of cellular schwannoma should be considered. MPNSTs are commonly negative for EMA, CK7, and CK19, which can differentiate this tumor from synovial sarcoma.

Answer 40

Cellular schwannomas can be mistakenly diagnosed as malignant due to their high cellularity, mitotic activity and occasional bone destruction. This entity is defined as a schwannoma that is composed predominantly of Antoni A areas (usually less than 10% Antoni B areas) with absence of Verocay bodies. These lesions occur in the deep soft tissues of the extremities in ~1/4 of cases. Histologically, cellular schwannomas show short, intersecting fascicles and whorls of Schwann cells that can be arranged in a herringbone pattern. Mitotic activity can be seen, but is usually low. Cellular schwannomas lack the hyperchromatic and anaplastic cells seen in MPNSTs and display strong positivity for S100 protein.

Answer 41

Clear cell sarcoma of soft tissue is a rare tumor that affects the extremities in young adults and shows melanocytic differentiation. This tumor is usually associated with tendons or aponeuroses and presents as a slow growing mass. Microscopically, the tumor grows in a uniform, nested to fascicular pattern with thin fibrous septa. Tumor cells are polygonal to spindle-shaped with abundant clear or eosinophilic cytoplasm and prominent nucleoli. Multinucleated giant cells are present in half of cases, and intracellular melanin can occasionally be seen. Clear cell sarcoma is positive for S100 protein, HMB45, and other melanocytic markers and shows a reciprocal translocation, t(12;22)(q13;q12), that results in EWS/ATF1 gene fusion.

Answer 42

ALHE can have a striking histologic similarity to KL. ALHE is present mostly in Caucasians and can be confused with early stage KL. ALHE more often affects females and is seen in soft tissues and superficial dermis forming clusters of eosinophilic cells. ALHE typically presents as cutaneous papules rather than a mass lesion, and histology reveals non-nodal collections of eosinophils with hypertrophic endothelial cells that protrude and occlude vascular lumina in a tombstone pattern. Lymphadenopathy, which is an essential feature in KL, is not frequently seen in ALHE.

Answer 43

Myxoid liposarcoma and round cell liposarcoma were historically considered separate subtypes of liposarcoma. The frequent transition areas between myxoid liposarcoma and round cell areas in the same tumor, along with the shared t(12;16)(q13;p11) chromosomal translocation, support a single classification as myxoid/round cell liposarcoma. The translocation results in fusion of the FUS (TLS) and CHOP genes on chromosomes 12 and 16, respectively. Myxoid/round cell liposarcoma accounts for approximately 30–35% of liposarcomas. These tumors occur almost exclusively in adults, usually in the third to eighth decade with a male preponderance (male: female ratio of 3:1). Myxoid/round cell liposarcoma is somewhat unusual among soft tissue tumors in that it often metastasizes to unusual sites such as the soft tissue of the trunk or axilla before metastasizing to the lung.

Answer 44

The three most common sarcomas in the retroperitoneum are liposarcoma, leiomyosarcoma, and pleomorphic sarcoma (malignant fibrous histiocytoma).

Answer 45

In small biopsy specimens or cases with few, if any, lipoblasts, the detection of the t(12;16) translocation may be extremely helpful in the differential diagnosis. Fresh tissue placed in RPMI may be used for complete karyotyping. Fluorescence in situ hybridization (FISH) for chromosome 12 (CHOP, 12q13) and reverse transcriptase polymerase chain reaction (RT-PCR) for the FUS-CHOP fusion transcripts may be performed on formalin-fixed paraffin-embedded tissue. Immunohistochemistry is of limited utility.

Answer 46

Embryonal rhabdomyosarcoma is a primitive soft tissue sarcoma with small blue cells resembling embryonic skeletal muscle. It is the most common rhabdomyosarcoma (RMS) subtype (65% of RMS cases), and usually occurs in children ages 3-10 years in the head and neck (nasal and oral cavities, orbit, ear), prostate or paratesticular regions. Gangliorhabdomyosarcoma is a rare variant of embryonal rhabdomyosarcoma which also has cells exhibiting neuronal differentiation. A related entity is malignant ectomesenchymoma, composed of a malignant mesenchymal component (often but not exclusively rhabdomyosarcoma) and a neuroectodermal component (often ganglion cells or neuroblasts). The differential diagnosis includes Triton tumor (rhabdomyosarcoma plus MPNST), Wilms tumor, and teratoma. Optimal treatment is not well defined for this rare tumor, but most authors recommend a combination of surgery, radiotherapy, and a chemotherapeutic protocol based on the RMS component.

Answer 47

Hibernoma is an uncommon benign tumor of brown adipose tissue, representing approximately 1.1% of all adipocytic tumors and occuring predominantly in adults, with a peak incidence in the 3rd to 4th decade.

Answer 48

Granular, eosinophilic cells; multivacuolated cells; and univacuolated white fat cells. Intermediate forms of the brown fat cells are also present, ranging in appearance from cells with abundant granular, eosinophilic cytoplasm and few vacuoles to paler cells with multiple intracytoplasmic vacuoles containing oil red O-positive lipid droplets.

Answer 49

1. The "typical" hibernoma, which includes pale cell (pale hibernoma cells and pale white fat cells), mixed cell (an even mixture of pale and eosinophilic hibernoma cells), and eosinophilic cell (a predominance of eosinophilic hibernoma cells) subtypes. 2. The "lipoma-like" variant, with only scattered hibernoma cells among abundant white adipose tissue. 3. The "myxoid" variant, with tumor cells separated by acellular myxoid stroma. 4. The "spindle cell" variant, which has combined features of hibernoma and spindle cell lipoma (interspersed spindled cells and thick collagen bundles).

Answer 50

Cytogenetically, hibernomas are often associated with rearrangements of chromosomal bands 11q13-21; however, other benign lipomatous tumors may also display such abnormalities. By IHC, hibernomas are variably positive for S100 protein and spindle cell components are positive for CD34.

Answer 51

Histopathological diagnosis of myelolipoma involves demonstration of (a) lipomatous compartment, which is composed of mature adipocytes and (b) hematopoietic compartment, which includes any of the three lineages (myeloid, erythroid, and megakaryocytic). An exclusively lymphocytic, monocytic or histiocytic cell infiltration will not constitute the myeloid (marrow) compartment's equivalence. In addition, caution should be exercised in tumors that show only mature myeloid cells (granulocytes, or eosinophils); granulocytic cells can be part of the inflammatory infiltrate within a lipoma, and do not constitute a true myeloid compartment. Similarly, immature myeloid cells, such as blasts, can be present in soft tissue involvement by leukemia (myeloid sarcoma), and hence should be interpreted with caution. Unequivocal proof of myeloid (marrow) compartment of myelolipoma is provided by the presence of erythroid colonies and/or megakaryocytic cells.

Answer 52

Thorotrast (radiologic contrast material), arsenic (such as from insecticide exposure), and vinyl chloride (typically from polyvinyl chloride polymerization plants). However, since the use of these carcinogens has dramatically decreased, most current cases of hepatic angiosarcomas are sporadic in nature or are associated with anabolic steroid use.

Answer 53

Thrombocytopenia (secondary to entrapment of platelets in the tumor/Kasabach-Meritt syndrome). Microangiopathic hemolytic anemia (due to red cell fragmentation in the tumor). Disseminated intravascular coagulation.

Answer 54

The 2 most widely used grading systems are the FNCLCC (Federation Nationale des Centre de Lutte Contre la Cancer) and NIH systems. The CAP recommends the French system over the NIH system for reasons of ease of use/reproducibility and perhaps slightly superior performance. The FNCLCC grade is determined by 3 parameters: differentiation (histology specific), mitotic activity, and extent of necrosis. Each parameter is scored: differentiation 1-3, mitotic activity 1-3, and necrosis 0-2. The scores are summed to designate grade: score of 2 or 3 = grade 1, score of 4 or 5 = grade 2, and score of 6-8 = grade 3. The tumor differentiation score is histology specific and is generally scored as follows: Score 1 is for sarcomas closely resembling normal, mature mesenchymal tissue. Score 2 is for sarcomas of definite histologic type. Score 3 is for synovial sarcomas, embryonal sarcomas, undifferentiated sarcomas, and sarcomas of unknown/doubtful tumor type.

Answer 55

Liposarcoma. Mouse Double Minute 2 homolog (MDM2) is a protein that is a negative regulator of p53 encoded by the MDM2 gene. DNA Damage Inducible Transcript 3, AKA C/EBP homologous protein (CHOP), is a transcription factor encoded by the DDIT3 gene.

Answer 56

Lymphoma with artifactual signet ring cells due to cytoplasmic shrinkage (CD45 is usually positive in lymphoma). Metastases from breast or lung (clinical history, plus the use of appropriate immunostains such as TTF1 or GCDFP-15 is helpful). Reactive epithelial atypia associated with radiation treatment or chemotherapy. Xanthoma.

Answer 57

Elastofibroma usually presents as a painless, slow growing mass which is discovered incidentally. Most cases of elastofibroma are localized to the lower subscapular region, are nonadherent to the overlying skin and surrounding musculature, but have irregular margins and are often adherent to the posterior chest wall. The scapula may overlie the lesion thereby masking it. This lesion is most often diagnosed in the elderly population, with greater than 90% female predominance. Elastofibroma is thought to be a degenerative, non-neoplastic pseudotumor arising as a result of excessive collagen deposition and abnormal elastogenesis secondary to mechanical irritation of the tissue plane between the inferior edge of the scapula and the chest wall. Some patients provided a history of significant manual labor involving the shoulder girdle possibly accounting for the right-sided predominance of this lesion. A genetic predisposition to this condition has been suggested. Its complete resection is considered curative with no tendency to recur.

Answer 58

Histologically the mass is hypocellular, patternless and contains a mixture of haphazardly arranged collagen bundles, myxoid matrix and elastic fibers. Adipose tissue can be seen within the lesion. The elastic fibers have a characteristic beaded and fragmented appearance. This pattern as well as the enormous number of elastic fibers can be highlighted by an elastic stain. Elastofibroma is immunohistochemically positive for vimentin, and negative for S-100, actin and desmin.

Answer 59

Spindle cell lipoma also occurs in the shoulder/back region, but it is more common in men. It shows thick, rope-like collagen bundles and characteristic spindled cells, often admixed with mast cells. Low grade myxofibrosarcoma is rarely seen in the trunk region. It characteristically shows a distinct multinodular growth pattern, prominent myxoid matrix, curvilinear blood vessels and cytologic atypia. Nuchal-type fibroma is more common in men and shows thick, haphazardly arranged collagen fibers and elastic-poor fibrous tissue. Many cases are associated with diabetes mellitus. Desmoid-type fibromatosis shares the infiltrative pattern and poor margination with elastofibroma. However, it is usually hypercellular and associated with skeletal muscle. Elastofibroma in contrast is not muscle invasive. A myxoid variant of neurofibroma certainly enters the differential diagnosis but immunohistochemical staining for S-100 and the typical wavy nuclei help to distinguish it from elastofibroma.

Answer 60

The differential diagnosis of Wilms tumor includes other primary renal tumors of childhood, including malignant rhabdoid tumor, congenital mesoblastic nephroma (classic and cellular variants), clear cell sarcoma of the kidney, and renal cell carcinoma. Other diagnostic considerations include other small cell tumors of the kidney (synovial sarcoma, primitive neuroectodermal tumor of the kidney, desmoplastic small round cell tumor, neuroblastoma, lymphoma) and a variety of benign tumors (cystic nephroma, infantile ossifying tumor of the kidney, oncocytoma, and others).

Answer 61

A t(12;16)(q13;p11) chromosomal translocation, resulting in fusion of the FUS (TLS) and CHOP genes on chromosomes 12 and 16, respectively.

Answer 62

Myxoid liposarcoma and round cell liposarcoma were historically considered separate subtypes of liposarcoma. The frequent transition areas between myxoid liposarcoma and round cell areas in the same tumor, along with the shared t(12;16)(q13;p11) chromosomal translocation, support a single classification as myxoid/round cell liposarcoma. The translocation results in fusion of the FUS (TLS) and CHOP genes on chromosomes 12 and 16, respectively. Myxoid/round cell liposarcoma is the most common subtype of liposarcoma, accounting for approximately 30–35% of liposarcomas. These tumors occur almost exclusively in adults, usually in the third to eighth decade with a male preponderance (male: female ratio of 3:1). Myxoid/round cell liposarcoma is somewhat unusual among soft tissue tumors in that it often metastasizes to unusual sites such as the soft tissue of the trunk or axilla before metastasizing to the lung. Lymph node metastases are also more common in myxoid liposarcoma than many other soft tissue malignancies.

Answer 63

AKA peripheral fibroma with calcification. Is a reactive proliferation of fibrous tissue with mineralization exclusive to gingiva. May be associated with chronic irritation. Origin is cells from periosteum and/or periodontal ligament. Micro: Cellular fibroblastic stroma with a mineralized component (trabecular bone, woven bone, dystrophic calcification, cementum, or a combination of the above). Surface may be ulcerated.

Answer 64

Proliferation of nerves, often in a plexiform pattern. Seen on tongue and lips most commonly. Most cases of multiple lesions are seen in patients with MEN2B. Micro: Nonencapsulated, with a haphazard distribution. Hyperplasia of nerve bundles. Prominent thickening of perineurium. DDx: Neurofibroma (may blend with surrounding tissue, has spindle cells with variable collagen). Traumatic neuroma (lacks the prominent perineurium seen in mucosal neuroma). Palisaded encapsulated neuroma (encapsulated at least partially, has spindle cells). Schwannoma (neurilemoma) (characteristic Antoni A and B areas, Verocay bodies, and hyalinized vessels).

Answer 65

Osteomyelitis AKA osteitis is inflammation or infection of bone and bone marrow. Top differential diagnoses include inflammatory reaction (inflammation part of fracture repair; present at tumor borders; lack of acute inflammation and dead bone), lymphoma (atypical lymphoid infiltrate with bone remodeling and dense fibrosis), sarcoid (noncaseating, tight, well-formed granulomas), bisphosphonate therapy (bone necrosis with death, followed by active remoderling; more often a chronic process), and radiation osteitis (bone necrosis and death with chronic inflammation).

Answer 66

Cherubism is an inherited disease characterized by progressive, painless, symmetrical expansion of the jaws, resulting in a cherubic facial appearance. M:F = 2:1, with 100% penetrance in males and 50-70% penetrance in females. Mutations in the SH3BP2 gene have been identified in about 80 percent of people with cherubism. In most of the remaining cases, the genetic cause of the condition is unknown. There are germline point mutations in the SH3BP2 gene on chromosome 4p16.3.

Answer 67

Postzygotic, somatic, activating missense mutations in GNAS1 gene coding for alpha subunit of stimulatory G protein are a consistent finding (~3/4 of cases). The GNAS1 gene is on chromosome 20q13.2-13.3. The abnormal G1 protein stimulates cAMP, and the osteoblastic cells expressing this mutation have a higher rate of DNA synthesis than normal cells. This abnormal growth leads to the formation of a disorganized fibrotic bone matrix with primitive bone formation, and lack of maturation to lamellar bone. Mineralization is also abnormal. There is a failure of the bone to align in response to mechanical stress. The extent of disease is related to the stage at which the postzygotic mutation in Gsα has occurred, whether during embryonic development or postnatally.

Answer 68

Fibrous dysplasia.

Answer 69

When McCune-Albright syndrome (hyperfunctioning endocrinopathies, including precocious puberty, fluctuating thelarchy, hyperthyroidism, growth hormone excess, rickets/osteomalacia; as well as skin hyperpigmentation/cafe au lait spots) is associated with intramuscular myxomas, it is called Mazabraud syndrome.

Answer 70

Embryonal rhabdomyosarcoma is the most common type (65% of RMS cases) and usually occurs in children ages 3-10 in the head and neck (nasal and oral cavities, orbit, ear), prostate or paratesticular regions. Subtypes of embryonal rhabdomyosarcoma include embryonal NOS, anaplastic, botryoid, and spindle cell, with embryonal NOS being the most common subtype (75%).

Answer 71

Embryonal rhabdomyosarcoma is the most common type of rhabdomyosarcoma (65% of RMS cases) and usually occurs in children ages 3-10 in the head and neck (nasal and oral cavities, orbit, ear), prostate or paratesticular regions. Subtypes of embryonal rhabdomyosarcoma include embryonal NOS, anaplastic, botryoid, and spindle cell, with embryonal NOS being the most common subtype (75%).

Answer 72

Osteitis deformans is a synonym for Paget disease of bone, which is a localized skeletal disorder characterized by osteoclasts of increased number and size containing multiple nuclei. There is excessive breakdown and formation of bone tissue. Most common sites of involvement are: pelvis (70%) > femur (55%) > lumbar spine (50-55%) > skull (40%) > tibia (30%).

Answer 73

False. Total serum alkaline phosphatase is elevated in over 85% of patients, and may be useful in monitoring the disease. Serum calcium, phosphorus, and aminotransferase are normal in Paget disease of bone.

Answer 74

Risk of secondary sarcoma is 4-10% in Paget disease of bone. Secondary sarcomas are generally high grade. The most common types are osteosarcoma and malignant fibrous histiocytoma, but fibrosarcoma and giant cell tumor of bone may also be seen.

Answer 75

Unknown. Infectious agents have been proposed based on electron microscopy data, but there is no conclusive proof. The disease occurs in familial clusters and sporadically. 15-40% of patients have a positive family history. Familial cases display an autosomal dominant pattern of inheritance with variable penetrance. Cytogenetic studies of families with Paget disease of bone have identified numerous involved chromosomal loci. Nongenetic factors are also involved in the appearance of the disease, as there is variable penetrance in families, and the fact that the disease has a highly localized nature.

Answer 76

Findings reflect the stage of disease. The initial stages are reflective of osteoclastic activity: numeous osteoclasts, increased vascularity, and numerous resorptive surfaces. Mid-stage shows a mix of patterns: osteoclastic resorption, increased vascularity, and numerous surfaces covered with active osteoblasts. End stage is primarily sclerotic.

Answer 77

AKA central giant cell granuloma AKA giant cell reparative granuloma AKA giant cell tumor. A potentially locally aggressive osteolytic lesion of gnathic bones. Neoplastic process is favored over reactive. The mandible is most commonly affected, with the anterior region more common. It frequently crosses the midline. Histologically, the tumor is composed of giant cells and stroma. The giant cells are most likely related to osteoclasts, can be focal collections or diffusely distributed, have variable size and shape, and can have up to 20 nuclei per cell. The stroma can be loosely arranged to fibrous, is cellular, and can have erythrocyte extravasation with hemosiderin. Do not confuse this entity with the other "giant cell tumor" which is thought to occur exclusively in long bones.

Answer 78

Simple bone cyst AKA traumatic bone cyst AKA traumatic bone cavity AKA solitary bone cyst AKA hemorrhagic cyst. Is a benign empty or fluid-filled cavity within bone most commonly in the mandible. Histologically, will have small fragments of fibrovascular connective tissue, small fragments of bone that are reactive with cellular trabeculae, red blood cells, rare giant cells, dystrophic calcifications, and no epithelial lining. The differential diagnosis includes developmental odontogenic cysts such as dentigerous cyst or lateral periodontal cyst (both have a cyst lining), or reactive odontogenic lesions such as radicular cyst (has a cyst lining) or periapical granuloma (dense inflammatory infiltrate).

Answer 79

A rare benign neoplasm of bone with lamellar bone formation, osteoblastic rimming, and connective tissue stroma. When cementum is present, the term cementifying fibroma or cemento-ossifying fibroma is used. It is a true neoplasm within fibro-osseous group, rather than a developmental anomaly. Considered on spectrum with fibrous dysplasia and osseous dysplasia. Peak in 2nd to 4th decades, with mean 31 years. M:F = 1:5. Mandible is most common site.

Answer 80

A rare benign neoplasm of bone considered on spectrum with fibrous dysplasia and osseous dysplasia, most common in mandible. Composed of variable amounts of fibrous tissue proliferation and calcifications. Evenly spaced spicules of woven bone with lamellar transformation at periphery and osteoblasts and osteoclasts surrounding spicules (osteoblastic rimming is prominent). Prominent calcified structures (ossicles, cementicles), which are eosinophilic or basophilic spherules of osteoid. Cellular, spindled cell stroma. Multinucleated giant cells can be seen. IHC is unnecessary, but Runx2 nuclear positivity in spindled cells and osteocalcin distributed throughout calcified structures. Molecular genetics: mutations in HRPT2 gene reported. DDx: Fibrous dysplasia (polyostotic helps to exclude OF; irregularly shaped trabeculae of immature woven bone without osteoblastic rimming). Active ossifying fibroma (AKA (aggressive) psammomatoid ossifying fibroma AKA juvenile active ossifying fibroma; highly cellular stroma with mitoses and psammomatous calcifications). Cemento-osseous dysplasia (African-Americans commonly affected, involves periodontal ligament; lacks osteoblastic rimming).

Answer 81

Well circumscribed but variably encapsulated. Broad range of appearances due to multiple architectural patterns (solid, myxoid, reticular, nested, cord-like). Typically composed of spindled or plasmacytoid cells; may have dominant cell type or mixed morphology; plasmacytoid cells with hyperchromatic, round to oval nuclei and abundant, eccentric eosinophilic cytoplasm (characteristic but not pathognomonic, as also seen in pleomorphic adenoma of palate). Although not common, clear, polygonal (epithelioid), or stellate cells may be seen. Background with variable collagenization; may contain abundant acellular mucoid stroma. Lacks chondroid or myxochondroid matrix. Lacks infiltration, perineural invasion, profound pleomorphism, necrosis, increased mitotic figures. IHC: Reactive with pan-CK, CK7, CK14, p63, GFAP, and S100. Variable reactivity with actin-sm, actin-HHF-35, SMHC, and calponin (actins reactive in spindled cells but typically nonreactive in plasmacytoid cells). Mutations of p53 have been observed. DDx: pleomorphic adenoma, myoepithelial carcinoma, spindled soft tissue neoplasm, plasmacytoma.

Answer 82

Some metabolic and reactive lesions of bone that are prone to be misinterpreted as neoplasms due to their peculiar clinical and morphologic features include brown tumor, osteomalacic fracture, hemophilic pseudotumor, reactive mixed mesenchymal pseudotumors of periosteal origin, avulsion injuries of bone, and pubic osteolysis.

Answer 83

Brown tumors of bone, which are non-neoplastic mass lesions, can arise out of the setting of primary, secondary, and tertiary hyperparathyroidism.

Answer 84

Brown tumors are non-neoplastic mass lesions that develop as a complication of hyperparathyroidism. They usually develop in adults in the 3rd to 4th decades. M

Answer 85

Histologically, they have a lobular architecture defined by fibrous septa that may contain trabeculae of reactive woven bone. The lobules are composed of an admixture of plump fibroblasts, extravasated RBCs, hemosiderin-laden macrophages and scattered osteoclast-type giant cells, which freuently cluster around areas of hemorrhage. This bloody mass of reactive tissue erodes the endosteum, thinning and expanding the cortex as the periosteum deposits new bone. In sever cases, large blood-filled cysts develop, resulting in a lesion known as osteitis fibrosa cystica. Bone not involved by the tumor shows evidence of increased osteoclastic activity in the form of dissecting osteitis (osteoclasts boring through the center of bony trabeculae), cortical cutting cones (groups of osteoclasts tunneling into and expanding Haversian canals) and subperiosteal excavation. Treatment of the underlying abnormality abates the osteoclastic activity ad the lesion eventually regresses as it is filled in by newly deposited bone.

Answer 86

Giant cell reparative granuloma and giant cell tumor of bone. Giant cell reparative granuloma and brown tumor may have similar morphologic features and may be impossible to distinguish from one another by light microscopy alone. In giant cell tumor of bone, the mononuclear cells are not as spindled as the fibroblasts of a brown tumor and in contrast to a brown tumor, the nuclei of the mononuclear cells are morphologicallly identical to those in the osteoclasts.

Answer 87

Osteomalacia is defined as a defect in mineralization resulting in inadequate calcification of cortical and trabecular bone throughout the body. Osteomalacia is the term for this disorder in adults and in children it is known as rickets. It can be produced by numerous mechanisms, the most common of which is a vit D deficiency or a disturbance in its metabolism. Osteomalacia uncommonly causes bone fracture, being responsible for only 2% of hip fractures in the elderly. The type of fracture most commonly associated with osteomalacia is an insufficiency stress fracture which has been termed "Looser's zone" or "Milkman's fracture" by radiologists. Grossly, the Looser's zone is seen as a thin, linear, ill-defined sclerotic zone arising from the surface of the bone and extending into the trabecular bone of the medullary cavity. The zone itself is composed of large amounts of inadequately mineralized reactive bone that is a form of callus. The periosteum also has similar deposits of unmineralized reactive bone. The unmineralized callus inhibits osteoclastic resorption of the fracture framents, accounting for the observed poor healing. Histologically, this abundant reactive bone can resemble that seen in osteoid osteoma, osteoblastoma and osteosarcoma. Unlike osteoid osteoma and osteoblastoma, the bone in a Looser's zone is not arranged as a well circumscribed mass and, in contrast to osteosarcoma, there is no nuclear anaplasia.

Answer 88

A serious but rare (<2% incidence) lesion that occurs in the bones and deep soft tissues of patients with hemophilia, which can be confused with simple bone cyst, aneurysmal bone cyst, osteosarcoma, or angiosarcoma. Recurrent hemorrhages with reparative changes are responsible for the clinicopathologic manifestations. In bone, they may be intraosseous or sub-periosteal and usually develop in the femur, pelvis, and tibia in adults and the small bones of the hands in children. Histologically, areas of extensive hemorrhage, thrombus formation, bone destruction, and florid new bone formation characterize this lesion and, taken out of context, can be misinterpreted as malignant. Juxtacortical and intramuscular lesions exhibit central masses of organizing blood encased by a fibrous capsule that may be composed of 3 distinct layers: an inner hemosiderin-rich collagenous layer, a central layer of dense fibrous tissue, and an outer layer rich in elastin.

Answer 89

When a tendon is subjected to severe stress, the force transmitted across its osseous insertion can result in fracture of the bone at this site. These avulsion injuries are most common in young adults who engage in strenuous physical activity that produces forceful muscle contraction. An acute avulsion injury subjected to recurring stress can induce a chronic reparative process that may have features that simulate a neoplasm. These chronic avulsion lesions are frequently seen on the surfaces of the distal medial metaphysis of the femur, spines of the ilium, ischial apophyses, trochanters of the femur and along the insertion of the deltoid muscles into the proximal humeri. Histologically, the lesion is composed of reactive woven bone, cartilage, and fibrosis. The woven bone is rimmed by plump cytologically banal osteoblasts which in areas merges with lamellar bone. The component of cartilage may be fibrocartilaginous or hyaline and is frequently hypercellullar with foci of enchondral ossification. Histologic DDx includes soft tissue and intraosseous fibromatosis, and osteosarcoma.

Answer 90

A form of delayed union of a conservatively treated fracture that typically affects osteoporotic postmenopausal women who have experienced minor trauma to the area. Radiographically, there is soft tissue swelling and either single or multiple rapidly progressive destructive lesions of the pubic symphysis and rami in the background of osteoporosis. Bilateral involvement may also occur. The radiographic differential diagnosis includes metastatic carcinoma, chondrosarcoma, multiple myeloma, and myelosclerosis. Histologically, there is an admixture of reactive bone, cartilage, and fibrous tissue. The adjacent host bone of the pubis may show focal necrosis and osteoclastic and osteoblastic activity. The cellularity can cause confusion with chondrosarcoma and osteosarcoma.

Answer 91

Schwannoma > lipoma > hemangioma.

Answer 92

All histologic variants of hemangioma occur in salivary glands, but capillary (juvenile) hemangioma is most common. Hemangiomas account for 90% of parotid gland tumors in infants <1 yo are hemangioma. Capillary (juvenile) hemangiomas have M:F = 1:3, while cavernous hemangiomas tends to be seen more frequently in older males. Parotid gland involved in 90%, and up to 25% are bilateral. Pediatric tumors initially grow rapidly, but 75-95% spontaneously involute before 7 yo, and many earlier. Pharmacological therapy (corticosteroids and interferon) yields a response in up to 98% of cases. IHC: Endothelial cells pos for CD31, CD34, FVIIIRAg. Residual salivary ducts are keratin pos. GLUT1 pos in juvenile hemangiomas.

Answer 93

Spindle cell rhabdomyosarcoma is a rare variant of embryonal rhabdomyosarcoma that has a predilection for young males and most commonly involves the paratesticular region followed by head and neck. Histopathology demonstrates elongated spindle cells with fusiform to cigar-shaped nuclei and indistinct eosinophilic cytoplasm arranged in fascicles or whorls. Although the tumor demonstrates increased cellularity and moderate atypia, the microscopic and architectural patterns can allow this tumor to be confused with multiple entities, such as leiomyosarcoma, spindle cell carcinoma, desmoplastic melanoma, or fibrosarcoma, with important therapeutic implications. IHC workup demonstrates sarcomeric differentiation with reactivity for desmin, myogenin, and MyoD1 markers. Compared with other subtypes, the spindle cell variant in children is associated with a favorable outcome; however, in the adult population there does not appear to be any prognostic advantage.

Answer 94

Histopathology is dominated by a uniform cellular proliferation of elongated, spindle cells arrayed in fascicles or whorls demonstrating a herringbone growth pattern reminiscent of leiomyosarcoma. The cells have centrally located nuclei with blunted or fusiform ends, small to inconspicuous or prominent nucleoli, and eosinophilic fibrillar cytoplasm. Mitotic figures are easily appreciated, including atypical forms. Admixed with this population can be a second cell type of immature rhabdomyoblasts, usually comprising a small percentage of the total tumor. These cells exhibit eccentric nuclei and bright cytoplasmic eosinophilia; on occasion, cytoplasmic cross-striations can be observed. The presence of these cells should be an intimation of the diagnosis. Collagen fibers are frequently intermingled between the spindle cells; however, the degree is highly variable. The extent of collagen production has led some authors to subclassify SC-RMS into collagen-rich and collagen-poor forms. The subclassification does not appear to affect clinical outcome.

Answer 95

Poorly differentiated carcinoma. Melanoma/clear cell sarcoma. Glomus tumor. Gangliocytic paraganglioma. GI endocrine carcinoma. Extramedullary myeloid tumor. GI mucosal benign epithelioid nerve sheath tumor.

Answer 96

A rare benign cartilaginous bone tumor arising in young adults aged 15-25 years that often occurs in the metaphysis of long tubular bones or in the small bones of the feet. Grossly: well circumscribed, solid and glistening. It is often lobulated with zonation. Older tumors are more hyalinized. Microscopic: well circumscribed, hypocellular lobules of poorly formed hyaline cartilage composed of chondroblasts with abundant pink cytoplasm, and myxoid tissue with fibrous septae containing spindle cells and osteoclasts. Atypia is common, including large, hyperchromatic nuclei. Scattered calcification and osteoclast-like giant cells are present. At the periphery, the tumor is more cellular and vascular. No/rare mitotic activity. Tumors often have 6q13 rearrangements, with recurrent 6p25 and 6q25 anomalies.

Answer 97

Leukoerythroblastosis indicates severe disruption of the marrow by overwhelming infection, myelofibrosis, or bone marrow invasion by cancer, and may be associated with extramedullary hematopoiesis. A leukoerythroblastic reaction in infants can occur with severe hemolytic anemia (eg, erythroblastosis fetalis) or the rare bone disorder, osteopetrosis, in which failure of osteoclasts to resorb bone causes loss of hematopoietic marrow space and resultant extramedullary hematopoiesis.

Answer 98

Sclerosing Angiomatoid Nodular Transformation (SANT) of the spleen is a rare benign lesion of the spleen with unknown etiology. SANT is classically considered to be a female-predominant disease. Most lesions are found incidentally on imaging. Although SANT has specific imaging findings, the DDx from other splenic tumors or malignant lesions is very difficult. Histopathologically, these tumors reveal multiple confluent angiomatoid nodules; these nodules are surrounded by concentric collagen fibers exhibiting an inflammatory and myofibroblastic response and are accompanied by numerous erythrocytes and siderophages. The nodules are populated by endothelial cells, phenotypically recapitulating normal splenic vasculature, such as sinusoids, capillaries, and small veins. Nuclear atypia is minimal, mitotic figures are extremely rare, and necrosis is consistently absent. This lesion has a unique immunohistochemical profile characterized by CD34−CD31+CD8+ sinusoids, CD34+CD31+CD8− capillaries, and CD34−CD31+CD8− small veins. CD68 is positive in macrophages. Splenectomy is an effective technique for the management of SANT. Prognosis is good, with no recurrence after splenectomy.

Answer 99

Vascular neoplasms are the most common primary nonhematopoietic tumors of the spleen. They include hemangiomas, littoral cell angiomas, splenic hamartomas (SHs), lymphangiomas, hemangioendotheliomas, angiosarcomas, and Sclerosing Angiomatoid Nodular Transformation (SANT).

Answer 100

Skin, bones, GI tract.

Answer 101

CCS share many features with malignant melanoma, including expression of melanoma markers, but, in contrast to most melanomas, they lack BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations. In addition, most CCS show rearrangement of the EWSR1 (Ewing sarcoma breakpoint region 1) locus, which in most cases leads to fusion of the EWSR1 gene with the activating transcription factor-1 gene (ATF1) in a recurrent translocation, t(12;22)(q13;q12). This translocation is not present in melanoma. On rare occasions, CCS of soft tissues can also show EWSR1-CREB1 (cAMP responsive element–binding protein 1) gene fusion.

Answer 102

A rare, often cystic lesion that typically fills the nasal cavity and extends into the ethmoid sinuses. It is considered an upper respiratory tract analogue of chest wall mesenchymal hamartoma. Although benign, it may erode the cribriform plate, and have an intracranial component. It is more common in males (2/3), and typically affects children, with a mean age of 14 months. Histologically, there is well demarcated mature cartilage, myxoid stroma and spindle cells. There may also be focal osteoclast-like giant cells, aneurysmal bone cyst-like formations, and collagen fibers. DDx: aneurysmal bone cyst, chondroblastoma, chondromyxoid fibroma, fibrous dysplasia, osteochondromyxoma.

Answer 103

Capillary, or simple, lymphangiomas are usually found in superficial skin and composed of capillary-sized, thin-walled vessels. Cavernous lymphangiomas are subcutaneous lesions composed of mildly dilated large spaces that are larger than those seen in capillary lymphangiomas. Cystic hygromas are most common in the neck and composed of large, dilated, cystic lymphatic spaces. Combinations of the 3 types can sometimes be found in a single lesion. Differentiating lymphangiomas on the basis of histologic type appears without clinical implications.

Answer 104

Head and neck. Most are found in the skin and subcutaneous tissues, but they have also been described in the larynx, parotid gland, mouth, tongue, and tonsils.

Answer 105

The Ewing sarcoma breakpoint region 1 (EWSR1; also known as EWS) represents one of the most commonly involved genes in sarcoma translocations. In fact, it is involved in a broad variety of mesenchymal lesions which includes Ewing's sarcoma/peripheral neuroectodermal tumor, desmoplastic small round cell tumor, clear cell sarcoma, angiomatoid fibrous histiocytoma, extraskeletal myxoid chondrosarcoma, and a subset of myxoid liposarcoma. The fusion products between EWSR1 and partners usually results in fusion of the N-terminal transcription-activating domain of EWSR1 and the C-terminal DNA-binding domain of the fusion partner, eventually generating novel transcription factors.

Answer 106

Ewing's sarcoma/peripheral neuroectodermal tumor, desmoplastic small round cell tumor, clear cell sarcoma, angiomatoid fibrous histiocytoma, extraskeletal myxoid chondrosarcoma, and a subset of myxoid liposarcoma.

Answer 107

The Ewing sarcoma/PNET family of tumors is characterized by chromosomal translocations involving the EWSR1 gene on chromosome 22 with one of several members of the ETS family of transcription factors on various different chromosomes including 2, 7, 11, 17 and 21. The most common translocation (over 70% of cases in bone/soft tissue) is t(11;22)(q24;q12) which leads to the formation of the EWS-FLI1 fusion protein.

Answer 108

Typically in bone and soft tissues, PNET tumors with variant gene fusions (non-FLI1) are associated with a worse outcome.

Answer 109

The differential diagnosis of small round cell tumors of the kidney includes blastema-predominant Wilms tumors, lymphoblastic lymphoma, clear cell sarcoma, small cell carcinoma, monophasic synovial sarcoma, neuroblastoma, rhabdomyosarcoma, desmoplastic round cell tumor, rhabdoid tumor and extraskeletal Ewing sarcoma/PNET.

Answer 110

Bile ducts, bone, placenta, intestine.

Answer 111

Anodal mobility 1 = biliary. Anodal mobility 2 = bone. Anodal mobility 3 = placenta. Anodal mobility 4 = intestinal.

Answer 112

Bone alkaline phosphatase is produced by osteoblasts and reflects bone-forming activity.

Answer 113

Paget disease of bone.

Answer 114

Biliary: -, +. Bone: -/+++. Placenta: +++/-. Intestinal: +++/+. For sensitivity to heat/urea, think "bone burns, placenta persists."

Answer 115

The fastest is CK-BB (CK1). The slowest is CK-MM (CK3).

Answer 116

CK-MM is found in skeletal and cardiac muscle. Skeletal muscle is ~99% MM, and cardiac muscle is ~70% MM.

Answer 117

In normal subjects serum CK is almost 100% CK-MM isoenzyme, mostly from skeletal muscle.

Answer 118

CK-MB is found in skeletal and cardiac muscle. Skeletal muscle is ~1% MB, and cardiac muscle is ~30% MB.

Answer 119

Metabolic breakdown products of CK. With high-resolution electrophoresis, CK-MB resolves into 2 bands and CK-MM resolves into 3 bands. CK-MB2 and CK-MM3 are the tissue forms that are released from damaged myocardium. CK-MB1 is the plasma form and arises as a result of cleavage of a terminal lysine from the M peptide. CK-MM1and CK-MM2 are also cleavage products. A relative increase of tissue forms indicates a recent enzyme leak.

Answer 120

Troponins are a group of enzymes consisting of TnT, TnI, and TnC that are involved in mediating the actin-myosin interactions that result in muscle contraction.

Answer 121

While the same gene encodes cardiac and skeletal TnC, separate genes encode TnI and TnT in cardiac and skeletal muscle.

Answer 122

The specificity of CK-MB cannot equal that of troponin, because of false-positives from non-ischemic cardiac injury (pericarditis, myocarditis) and skeletal muscle disease (rhabdomyolysis, exercise). However, troponin is not useful to determine temporal stage of the MI (it remains elevated for up to 2 weeks following AMI), so serial CK-MB is still useful to see if the infarct is acute or resolving, or if there is a complication of MI such as extension of the infarct.

Answer 123

Facial angiofibromas (adenoma sebaceum) or forehead plaque. Nontraumatic ungual or periungual fibroma. >3 hypomelanotic macules. Shagreen patch (connective tissue nevus). Multiple retinal nodular hamartomas. Cortical tuber. Subependymal nodule. SEGA. Cardiac rhabdomyoma, single or multiple. LAM. Renal AML. Definite TSC is either 2 major features or one major plus 2 minor features.

Answer 124

Facial angiofibromas, collagenomas, lipomas, and meningiomas.

Answer 125

Bacillary angiomatosis, Kaposi sarcoma, palisaded myofibroblastoma, inflammatory pseudotumor of lymph node.

Answer 126

Coagulase-negative staphylococci (30-40%), S. aureus (10-20%), mixed flora (10%), streptococci (10%), GN bacilli (5%), enterococci (5%), and anaerobes (2-4%).

Answer 127

Monoarticular in children and adults: S. aureus. Polyarticular in young adults: N. gonorrhea.

Answer 128

S. aureus.

Answer 129

Usually polymicrobial: S. pyogenes and anaerobes such as B. fragilis.

Answer 130

Sporotrichosis: Sporothrix shenckii. Chromoblastomycosis: Phialophora, Cladosporium, Fonsacea. Lobomycosis: Loboa loboi. Phaeohyphomycosis: Exophiala jeanselmei, Phialophora, Wangiella dermatitidis. Eumycotic mycetoma: Exophiala, Wangiella, P. boydii (scedosporium). Rhinosporidiosis: Rhinosporidium seeberi.

Answer 131

Actinomyces, Nocardia, Streptomyces.

Answer 132

An uncommon low grade sarcoma of the hands and feet. It is composed of myxoid stroma, inflammation, and virocyte like cells. It affects men and women of all ages with a slow growing mass, usually in the hands or feet. The distinctive histologic feature is myxoid extracellular matrix with various types of tumor cells: Epithelioid or spindled (occasionally large with bizarre nuclei and prominent nucleoli resembling viral inclusions or Reed-Sternberg cells). Pseudolipoblasts (multivacuolated cells resembling pleomorphic lipoblasts due to cytoplasmic vacuoles containing myxoid material). Giant cells with emperipolesis. Also, minimal mitotic activity (0-1 MF/10 HPF), no atypical forms, no/rare necrosis. In addition, there are acute or chronic inflammatory cells and areas of fibrosis or hyalinized stroma.

Answer 133

t(2;13) with PAX3-FOXO1 (formerly known as FKHR) fusion and t(1;13) with fusion of PAX7 and FOXO1. As many as 20% of cases of alveolar rhabdomyosarcoma are negative for either translocation, and usually the solid variants.

Answer 134

Mammary analogue secretory carcinoma of the salivary gland, secretory carcinoma of the breast, infantile fibrosarcoma, cellular congenital mesoblastic nephroma, and some types of acute myelogenous leukemia.

Answer 135

Chondroblastoma is not associated with recurrent translocations or specific genetic abnormality.

Answer 136

LGFMS are often seen in young adult males with a median age in the third decade. But they are not uncommon in children, with up to a third of cases in those <18. LGFMS is typically a slow growing, painless deep soft tissue tumor of the extremities and trunk, superficial and visceral lesions can also be seen.

Answer 137

Vimentin positive. MUC4 positive. EMA focally positive. Negative: S100, GFAP, caldesmon, ALK-1, c-kit, nuclear beta-catenin.

Answer 138

The EWSR1-NR4A3 translocation t(9;22) is seen in about half of cases.

Answer 139

By definition, osteoblastoma must be larger than 2 cm. They may arise in any bone, but are most common in the posterior elements of the spine, femur, tibia, and bones of foot and ankle. The tumor is more common in males and tends to occur between the 2nd to 4th decades of life.

Answer 140

Aggressive osteoblastoma is composed of epithelioid osteoblasts that are 2-3x larger than conventional osteoblasts and have abundant eosinophilic cytoplasm and large vesicular nuclei with prominent nucleoli. It is often confused with osteosarcoma, but the well-demarcated nature of the tumor and the presence of osteoblastic rimming are features indicating the benign nature of the tumor. Pseudomalignant osteoblastoma is rare and characterized by neoplastic cells with large, bizarre, and degenerative nuclei. This variant is not associated with aggressive behavior but is often mistaken for osteosarcoma histology ally.

Answer 141

Most common form of skeletal dysplasia: achondroplasia (1 per 10-30,000 live births). Most common lethal form of skeletal dysplasia: thanatophoric dysplasia (1 per 35-50,000 births).

Answer 142

Fibroblast growth factor receptor 3, encoded by the FGFR3 gene on chromosome 4p16.3. 75% of cases are caused by sporadic new mutations.

Answer 143

Rarely, UES has arisen either in a preexisting MHL or following incomplete excision of MHL.

Answer 144

Lipoblastomas are characterized by rearrangements of 8q11-13 involving the PLAG1 gene.

Answer 145

Hibernomas are rare neoplasms that account for 1.6% of benign lipomatous tumors. Despite the fact that brown fat is most abundant in neonates, hibernomas are most common in adults, with a peak incidence between the 3rd and 4th decades. Only 5% occur in children 2-18 yo. There is a slight male predominance. The most common location is the thigh, followed by the shoulder, back, neck, chest, arm, abdominal cavity, and retroperitoneum.

Answer 146

AGS is a multisystem disorder with AD inheritance and variable penetrance and expressivity. The traditional diagnostic criteria have consisted of paucity of the interlobular bile ducts in association with 3 of 5 major findings, including chronic cholestasis, cardiac disease (most frequently peripheral pulmonary artery stenosis), skeletal manifestations (short stature, butterfly vertebrae), ocular abnormalities (most commonly posterior embryotoxon, a circular opacity of the posterior peripheral cornea), and characteristic facial features (triangular face with a prominent forehead, deep-set eyes, a pointed chin, and a straight nose with a bulbous tip). Mutations are in the JAGGED1 (JAG1) gene.

Answer 147

Turcot syndrome/APC gene mutations: medulloblastoma, rarely ependymoma. Tuberous sclerosis: subependymal giant cell astrocytoma. Von Hippel Lindau disease: hemangioblastoma. Li-Fraumeni syndrome (with germline TP53 mutations): medulloblastoma, astrocytic tumors, meningioma, schwannoma, choroid plexus tumors, and central PNET. NF type 1: optic glioma, astrocytoma, glioblastoma multiforme. NF type 2: multiple meningiomas, bilateral vestibular schwannomas, spinal ependymomas. Gorlin syndrome: desmoplastic/nodular variant of medulloblastoma.

Answer 148

No. Lipoblasts can also be seen in benign tumors such as lipoblastoma and lipoblastic nerve sheath tumor.

Answer 149

Clear cell sarcoma of soft parts: t(12;22)(q13;q12) - EWSR1-ATF1. Clear cell sarcoma (gastrointestinal): t(2;22)(q33;q12) - EWSR1-CREB1.

Answer 150

Most common in adrenal gland. Occasional cases in extraadrenal locations (retroperitoneum, presacral region, mediastinum, lung, liver, spleen, testis).

Answer 151

Uncommon fibrocollagenous lesion classically arising in cervicodorsal region. However, it is not restricted to the nuchal region so the term nuchal-type fibroma can be used. Some cases are linked to FAP/Gardner syndrome. The sporadic lesions are often nuchal, seen in 3rd-5th decades, and have striking male predominance. The Gardner-associated cases mostly involve trunk, head and neck, and extremities, are seen in infants to adolescents, and have no gender predominance.

Answer 152

Rare fibroblastic/myofibroblastic neoplasm consisting of a benign proliferation of fibroblasts and myofibroblasts containing scattered eosinophilic inclusion bodies that occur on the digits of children.

Answer 153

DF: CD34-, CD163+, FXIIIA+. DFSP: CD34+, CD163-, FXIIIA+/-.

Answer 154

Increased fibrofatty tissue infiltrating and surrounding nerves. Seen predominantly in children. Affects palmar surface of hand, wrist, or forearm, with median nerve and branches most commonly affected. Histologic appearance: Adipose tissue and fibrous tissue infiltrating around and between nerve branches and along perineurium. Epineurial and perineurial fibrous thickening. Perineurium can become hyperplastic (concentric layers, "onion bulb" intraneural hyperplasia). Nerve bundles become separated, atrophic in longstanding cases. DDx: Lipoma of nerve (circumscribed and confined within nerve). Neurofibroma (proliferation of neural elements with no fatty component). Neuroma (increased number of nerve bundles with no fatty component). Lipomatosis (usually affects skin and subcutis and spares nerves).

Answer 155

Osteopoikilosis, which may be inherited in an AD fashion. Bone islands in osteopoikilosis are histologically identical to sporadic, solitary bone islands.

Answer 156

For bone tumors, metastases are far more common than primary bone tumors in a ratio of 25:1. The 5 most common primary sites are lung, breast, prostate, kidney, and thyroid. After lungs and liver, skeleton is 3rd most frequent site of metastatic disease.

Answer 157

Giant cell tumors of bone account for 20% of all benign bone tumors and 5% of all bone tumors, malignant and benign.

Answer 158

GCTs of bone occur in skeletally mature individuals, usually young adults 20-40 yo, and are only rarely identified in children and are extremely rare in the elderly. ~50% arise in the knee, distal femur and proximal tibia, followed by the fibular head, the proximal femur, the distal radius and the sacrum. The lesion is always epiphyseal or metaepiphyseal; it is only purely metaphyseal in rare cases that occur in childhood before closure of the growth plate.

Answer 159

While no specific translocation or chromosomal anomalies are found in GCT, normal karyotypes are rarely encountered. The most frequent genetic abnormality seen in giant cell tumor of bone is reduction in telomere length (11p, 13p, 14p, 15p, 19q, 20q, 21p). Telomeric fusion is detected in ~70% of GCT. A higher incidence of chromosomal anomalies have been reported for recurrent benign GCT or metastatic GCT than for GCT cured after initial surgery. There are no known genetic syndromes predisposing to giant cell tumor.

Answer 160

Ollier disease (enchondromas, chondrosarcoma). Mafucci syndrome (enchondromas, chondrosarcoma). Bloom syndrome (osteosarcoma). Li-Fraumeni (osteosarcoma). Rothmund-Thompson syndrome (osteosarcoma). Werner syndrome (osteosarcoma). McCune-Albright syndrome (polyostotic fibrous dysplasia, osteosarcoma). Mazabraud syndrome (polyostotic fibrous dysplasia, osteosarcoma).

Answer 161

Ollier disease (enchondromas, chondrosarcoma). Mafucci syndrome (enchondromas, chondrosarcoma). Bloom syndrome (osteosarcoma). Li-Fraumeni (osteosarcoma). Rothmund-Thompson syndrome (osteosarcoma). Werner syndrome (osteosarcoma). McCune-Albright syndrome (polyostotic fibrous dysplasia, osteosarcoma). Mazabraud syndrome (polyostotic fibrous dysplasia, osteosarcoma).

Answer 162

In Ewing sarcoma, a t(11;22) producing EWSR1/FLI-1 is present, while in desmoplastic small round cell tumor a different t(11;22) producing EWSR1/WT1 is present.

Answer 163

~75% of alveolar rhabdomyosarcomas have a balanced translocation involving chromosomes 2 and 13 or chromosomes 1 and 13. The most common, t(2;13)(q35;q14) generates a fusion gene and corresponding fusion protein involving the genes PAX3 and FKHR (AKA FOXO1). The second most common, t(1;13)(p36;q14), generates a fusion gene and protein involving PAX7 and FKHR. Several other translocations have been described involving the PAX3 and PAX7 genes. The remaining 25% of cases do not have translocations identifiable by karyotyping.

Answer 164

Patients with familial adenomatous polyposis develop juvenile nasopharyngeal angiofibromas 25x more frequently than an age-matched population.

Answer 165

Positive for androgen receptors (75%), rarely for PR, and negative for ER. Other positive stains include beta-catenin, MSA, CD31 and CD34 in the vascular endothelium, and CD117 in mast cells.

Answer 166

In addition to colorectal polyps, ~90% of patients with FAP also develop gastric and duodenal polyps. Other systemic manifestations of FAP include osteomas (80%), congenital hypertrophy of the retinal pigment epithelium (70-80%), desmoid-type fibromatosis (15%), and dental abnormalities. Risk of malignancy is increased relative to the general population for hepatoblastoma (847x), duodenal carcinoma (330x), ampullary carcinoma (123x), nasopharyngeal adenofibroma (25x), thyroid carcinoma (7.6x) (specifically, the cribriform morular variant of papillary thyroid carcinoma is strongly associated with APC gene mutations), brain tumors (7x), and pancreatic carcinoma (4x).

Answer 167

The association of adenomatous polyposis with prominent skin and soft tissue manifestations (osteomas, epidermal cysts, lipomas, and soft tissue fibromatosis) has been designated Gardner syndrome. The association of adenomatous polyposis and a brain tumor (most commonly medulloblastoma, ependymoma, or anaplastic astrocytoma) is called Turcot syndrome.

Answer 168

~66% of MPNSTs arise from neurofibromas, often of the plexiform type. ~25-75% of MPNSTs arise in the setting of neurofibromatosis type 1.

Answer 169

Epithelioid variant, glandular variant, and malignant triton tumor (MTT)/MPNST with rhabdomyosarcomatous differentiation. The epithelioid variant is rare and not associated with NF1. The glandular variant contains foci of gland-forming epithelium that resembles intestine and may be keratin- and/or CEA-positive, often with intra- or extracellular mucin. Scattered NE cells immunoreactive for chromogranin, somatostatin, and serotonin are also a common finding. ~75% are associated with NF1. The MTT is 3-4x more common than the glandular variant and is often characterized by divergent mesenchymal differentiation with areas of chondrosarcoma, osteosarcoma, or epithelial glands. ~60% are associated with NF1.

Answer 170

Both typically have complex karyotypic abnormalities that are both numerical and structural, but no consistent karyotypic pattern has been identified. On a molecular level, homozygous deletions of the CDKN2A gene, which encodes the p16 cell cycle inhibitory molecule, occurs in the progression of neurofibromas to MPNST, being identified in ~50% of MPNST but not in neurofibromas.

Answer 171

Hemangioma of orbit. Most cases occur in adults, and most are cavernous.

Answer 172

Secondary hyperparathyroidism (AKA pseudohypoparathyroidism) is due to peripheral resistance to the action of PTH. The PTH level is normal to high, calcium level is low, and phosphate is high. This persistent hyperparathyroid state produces marked activation of osteoclasts in bone, leading to so-called brown tumors of bone (renal osteodystrophy).

Answer 173

Can be used in ALL or small B cell lymphoproliferative disorders when CD20 may be negative or after rituximab (anti CD-20) therapy. Can be used in infarcted lymphomas. Can be used to differentiate preB lymphoblastic lymphoma from Ewing’s sarcoma.

Answer 174

Lead enters the body through inhalation and ingestion. About 95% of ingested lead is distributed in erythrocytes and bone. Some also goes to the kidney where it is toxic to renal tubular cells.

Answer 175

Avascular necrosis of bone and proliferative retinopathy.

Answer 176

No. KS is the most common HIV-associated malignancy, leading to angiosarcomatous change of epithelial and mucous membrane-associated connective tissue. Although specifically due to the HHV8 virus, it is considered to be due to the convergence of immune evasion, oncogenesis, inflammation and angiogenesis. Although HHV8 was first detected in, and is usually associated with HIV+ patients, KS can be initiated through non-viral mechanisms, including iatrogenic immunosuppression and elevated expression of cytokines and angiogenic growth factors.

Answer 177

It typically occurs in the head and neck (tongue and oral cavity) and extremities. Microscopically, it is circumscribed to diffusely infiltrative with fascicles or storiform growth of spindled tumor cells. Cells have ill defined, pale eosinophilic cytoplasm, fusiform nuclei that are either elongated or wavy with evenly distributed chromatin or round and vesicular with indentations and small nucleoli. There is usually at least focal nuclear atypia with hyperchromasia and irregular nuclear membranes. The stroma is collagenous with prominent hyalinization, and numerous thin walled capillaries may be present. There are no histiocytic giant cells, or prominent inflammation. Mitotic activity is 1-6 mitoses/10 HPF. IHC: At least one myogenic marker is positive, and tumor cells are negative for h-caldesmon.

Answer 178

Eruptive xanthomas, presenting as crops of yellow pruritic papulonodules, are seen with elevated TG (chylomicrons or VLDL). Tendinous (tuberous) xanthomas are seen near the knees or elbows and appear when there are simultaneous elevations in TG and cholesterol (elevated IDL). Xanthelasma are yellow periorbital papules that are associated with high cholesterol (LDL).

Answer 179

Insulinoma. Nesidioblastosis. ILGF-like hormone secreting tumors (sarcomas, HCC). Advanced malignancy. Anti-insulin receptor antibodies. Autoimmune insulin syndrome. Post-gastric surgery. Drug induced (insulin, sulfonylureas, alcohol, quinine, salicylates, haloperidol, beta blockers, quinolones, pentamidine, ACE inhibitors, IGF-1). Critical illness such as hepatic/renal/cardiac failure, sepsis, inanition (def: an exhausted condition resulting from lack of food and water or a defect in assimilation; starvation). Hormone deficiency (cortisol, glucagon and epinephrine in insulin-deficient DM). Inborn errors of metabolism (glycogen storage disease, hereditary fructose intolerance, galactosemia, carnitine deficiency). Starvation. Accidental, surreptitious, or malicious hypoglycemia.

Answer 180

Glycogen. So the cytoplasm will be PAS+ diastase sensitive.

Answer 181

Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. This tumor causes hypoglycemia by the secretion of a prohormone form of insulin-like growth factor II. Only about 5% of SFTs are associated with the syndrome.

Answer 182

Epithelioid sarcoma and clear cell sarcoma of soft parts.

Answer 183

Cytogenetic: Complex. Molecular: IDH1 and IDH2 mutations.

Answer 184

t(11;22)(q24;q12) / EWSR1-FLI1 fusion. t(21;22)(q12;q12) / EWSR1-ERG fusion. t(2;22)(q33;q12) / EWSR1-FEV fusion. t(7;22)(p22;q12) / EWSR1-ETV1 fusion. t(17;22)(q12;q12) / EWSR1-E1AF fusion. inv(22)(q12q12) / EWSR1-ZSG. t(16;21)(p11;q22) / FUS-ERG. t(2;16)(q35;p11) / FUS-FEV.

Answer 185

Intermediate (locally aggressive): chondromyxoid fibroma, atypical cartilaginous tumor/chondrosarcoma grade I. Intermediate (rarely metastasizing): chondroblastoma. Malignant: chondrosarcoma (grade II, grade III), dedifferentiated chondrosarcoma, clear cell chondrosarcoma, mesenchymal chondrosarcoma.

Answer 186

Intermediate (locally aggressive): osteoblastoma. Intermediate (rarely metastasizing): none. Malignant: Osteosarcomas - low-grade central, conventional (chondroblastic, fibroblastic, osteoblastic), telangiectatic, small cell, low grade central, secondary, parosteal, periosteal, high grade surface.

Answer 187

Intermediate (locally aggressive): desmoplastic fibroma of bone. Intermediate (rarely metastasizing): none. Malignant: fibrosarcoma of bone.

Answer 188

Intermediate (locally aggressive): epithelioid hemangioma. Intermediate (rarely metastasizing): epithelioid hemangioma. Malignant: epithelioid hemangioendothelioma, angiosarcoma.

Answer 189

Low grade central osteosarcoma: Cytogenetic events - simple; Molecular events - MDM2 amplification. Parosteal osteosarcoma: Cytogenetic events - ring chromosomes; Molecular events - 12q13-15 amplification. High grade osteosarcoma: Cytogenetic events - complex; Molecular events - ?.

Answer 190

Cytogenetic events: t(X;17)(p11;q25). Molecular events: TFE3-ASPL fusion.

Answer 191

Cytogenetic events: t(16;17)(q22;p13). Molecular events: CDH11-USP6 fusion.

Answer 192

t(12;16)(q13;p11) / FUS-ATF1 fusion. t(12;22)(q13;q12) / EWSR1-ATF1 fusion. t(2;22)(q33;q12) / EWSR1-CREB1 fusion.

Answer 193

t(9;22)(q22;q12) / EWS-NR4A3 fusion. t(9;17)(q22;q11) / TAF2N-NR4A3 fusion. t(9;15)(q22;q21) / TCF12-NR4A3 fusion.

Answer 194

Cytogenetic events: ring form of chromosomes 17 and 22, t(17;22)(q21;q13). Molecular events: COL1A1-PDGFB fusion.

Answer 195

t(1;2)(q22;p23) / TPM3-ALK fusion. t(2;19)(p23;p13) / TPM4-ALK fusion. t(2;17)(p23;q23) / CLTC-ALK fusion. t(2;2)(p23;q13) / RANB2-ALK fusion.

Answer 196

Complex with frequent deletion of 1p.

Answer 197

Ring form of chromosome 12.

Answer 198

Inversion chromosome 12 / NAB2-STAT6.

Answer 199

Intermediate (locally aggressive): superficial fibromatoses (palmar/plantar), desmoid-type fibromatoses, lipofibromatosis, giant cell fibroblastoma. Intermediate (rarely metastasizing): dermatofibrosarcoma protuberans (fibrosarcomatous DFSP and pigmented DFSP), malignant solitary fibrous tumor, inflammatory myofibroblastic tumor, low-grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma/atypical myxoinflammatory fibroblastic tumor, infantile fibrosarcoma. Malignant: adult fibrosarcoma, myxofibrosarcoma, low grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma.

Answer 200

Intermediate (locally aggressive): Kaposiform hemangioendothelioma. Intermediate (rarely metastasizing): retiform hemangioendothelioma, papillary intralymphatic angioendothelioma, composite hemangioendothelioma, pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma, Kaposi sarcoma. Malignant: epithelioid hemangioendothelioma, angiosarcoma of soft tissue.

Answer 201

Intermediate (locally aggressive): none. Intermediate (rarely metastasizing): none. Malignant: malignant peripheral nerve sheath tumor, epithelioid malignant peripheral nerve sheath tumor, malignant Triton tumor, malignant granular cell tumor, ectomesenchymoma.

Answer 202

Intermediate (locally aggressive): hemosiderotic fibrolipomatous tumor. Intermediate (rarely metastasizing): atypical fibroxanthoma, angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumor, malignant ossifying fibromyxoid tumor, mixed tumor, malignant mixed tumor NOS, myoepithelioma, myoepithelial carcinoma, benign phosphaturic mesenchymal tumor, malignant phosphaturic mesenchymal tumor.

Answer 203

Synovial sarcoma NOS (spindle cell synovial sarcoma and biphasic synovial sarcoma), epithelioid sarcoma, alveolar soft part sarcoma, clear cell sarcoma of soft tissue, extraskeletal myxoid chondrosarcoma, extraskeletal Ewing sarcoma, desmoplastic small round cell tumor, extra-renal rhabdoid tumor, malignant mesenchymoma, neoplasms with perivascular epithelioid cell differentiation (benign PEComa NOS and malignant PEComa NOS), intimal sarcoma.

Answer 204

33-50% are thought to arise from preexisting neurofibromas, and 50% arise de novo. 50% of MPNSTs are associated with NF1.

Answer 205

The primary cilium is an antenna-like, nonmotile structure that extends from the surface of most mammalian cell types and is critical for chemosensing and mechanosensing in a variety of tissues including cartilage, bone, and kidney.

Answer 206

Microtubular axoneme organization in motile cilia follows a 9+2 assembly, where 9 doublets of microtubules surround a central pair; this arrangement allows specific movement patterns that can lead fluids toward a single direction in vivo by the interacting sliding of the different constitutive parts of doublets. Immotile cilia lack the microtubule central pair, thus cannot be motile.