Joints

Question 1

Functionally the three types of joints are

Answer 1

Functionally the three types of joints are synarthrosis (immovable), amphiarthrosis (slightly moveable), and diarthrosis (freely moveable).

Question 2

Rheumatology

Answer 2

Rheumatology is devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology diseases, collectively known as rheumatic diseases, which includes arthritis as well as lupus and Sjögren’s syndrome.

Question 3

Define entheses & enthesitis

Answer 3

Entheses are the insertion sites of tendons and ligaments to the bone surface and are essential structures for locomotion. Inflammation of the entheses (enthesitis) is a key feature of psoriatic arthritis and spondyloarthritis.

Question 4

Rheumatism

Answer 4

Musculoskeletal illness

Question 5

Rheumatoid arthritis genetics

Answer 5

Human leukocyte antigen
HLA-DR1 & HLA-DR4

Question 6

Citrullination

Answer 6

Amino acid arginine converted to citrulline in type II collagen and vimentin

Question 7

Common causes of malar rash are as follows:

Answer 7

Erysipelas
Cellulitis
Systemic lupus erythematosus
Rosacea
Pellagra
Dermatomyositis

Question 8

Erysipelas

Answer 8

Erysipelas is a type of skin infection that involves superficial lymphatics and upper dermis. The classic manifestation includes a painful, rapidly progressive, well-circumscribed, erythematous, shiny plaque accompanied by perifollicular edema and swelling (peau d’orange). Clinical presentations include acute onset of systemic symptoms, including fever, chills, and malaise.

Question 9

Cellulitis

Answer 9

Cellulitis is a skin infection that involves subcutaneous fat and deeper dermis. It is different from erysipelas in that it is less well-demarcated with little or no edema, and does not usually have systemic symptoms. In the presence of systemic symptoms, the course of the disease is more indolent.

Question 10

Pellagra

Answer 10

Pellagra is a systemic disease that results from a cellular niacin deficiency. It is defined by 4 “D’s”: dermatitis, dementia, diarrhea, and death. Dermatitis related to pellagra is a bilateral symmetric eruption on sun-exposed areas of the skin. During the acute phase, it may be painful to touch and eventually can become so striking clinically. In the absence of characteristic cutaneous manifestations, making the diagnosis of pellagra would be difficult.

Question 11

Poikiloderma

Answer 11

Poikiloderma is characterized by a tetrad of hyperpigmentation, hypopigmentation, epidermal atrophy, and telangiectasias. Poikiloderma may be seen in various dermatologic disorders and is not specific to DM Dermatomyositis (DM)

Question 12

Rosacea

Answer 12

Rosacea is a chronic inflammatory acneiform disease that involves facial area, especially in the middle age. Rosacea is considered as the most common cause of the malar rash. It usually occurs in fair-skin patients and involves the cheeks, chin, nose, forehead, eyelids, and nose. Classic findings include erythema, telangiectasia, and pustules or papules with no comedones. The rash of rosacea may be accompanied by episodes of flushing triggered by hot drinks, stress, or alcohol. Genetic factors and extrinsic factors are involved in the pathogenesis of the disease. Rosacea never causes systemic illness.

Question 13

What is CREST Syndrome

Answer 13

A less severe form of scleroderma is called limited scleroderma, or CREST syndrome. Characterized by:

Calcinosis: Calcium skin deposits

Raynaud’s phenomenon: A condition in which the blood vessels of the fingers and toes spasm when triggered by factors, such as cold, stress or illness. Cold, painful or numb fingers and toes result, which in severe cases may become gangrenous.

Esophageal dysfunction: Problems with the esophagus
Sclerodactyly: Skin damage on fingers
Telangiectasia: Spider veins

Question 14

Carcinoma

Answer 14

A cancer arising from the epithelial tissue of the skin or the lining of the internal organs

Question 15

Myelophthisic anemia

Answer 15

Myelophthisic anemia is anemia characterized by the presence of immature erythrocytes in the peripheral blood due to infiltration of the bone marrow by abnormal tissue. It is also one of the hypo-proliferative anemias because it results from inadequate production of red blood cells from the bone marrow.

Question 16

Schistocyts

Answer 16

Fragmented RBC seen in DIC and other hemolytic processes

Question 17

Spur cells

Answer 17

Liver failure

Question 18

Burr cells (echinocyte)
Look like Spur cells but less pointy

Answer 18

Kidney failure

Question 19

Smudge cells

Answer 19

CLL

Question 20

Blister cell rbc. What test should be ordered

Answer 20

G6pd deficiency

Question 21

Rule of threes

Answer 21

HGB=3X WBC & HCT=3xhgb

Question 22

Tear rbc dacrycyte

Answer 22

Myelofibrisis or infiltrative process

Question 23

Normal heart weight

Answer 23

0.4 to 0.5% of body weight
250 to 320 gm female
300 to 360 gm male

Question 24

Dermatological emergency

Answer 24

Rocky Mountain spotted fever
Necrotizing fasciitis
Toxic epidermal necrolysis
Stevens-Johnson syndrome

Question 25

Measles 3 histologic findings

Answer 25

Multinucleated giant cells
Multinucleated lymphocytes
Earthiness-Finkeldey cells (Multinucleated cells with eosinophilic nuclear inclusions are pathognomonic of measles)

Question 26

What % of follicles need to be micro to be considered a microfillicular pattern

Answer 26

> 50%

Question 27

Molecular mutation in invasive papillary thyroid carcinoma both conventional and follicular variant

Answer 27

BRAFV600E-type includes:
BRAFV600E
BRAF fusion
RET fusion
ALK fusion
NTRK fusion

Question 28

Encapsulated follicular variants of PTC

Answer 28

RAS-type including:
H/K/NRAS mutation
EIF1AX mutation
THADA fusion
BRAFK601E
PAX8::PPARgamma fusion

Question 29

Serology in chronic lymphocytic thyroiditis

Answer 29

Antimicrosomal ABS (95%)
Antithyroglobulin ABS (60-70%)

Question 30

Hyalinizing trabucular tumor of the thyroid

Answer 30

PAC8::GLIS Gene Fusion
Rare
Tends to arise in background of lymphocytic thyroiditis

Question 31

Mimics of oncocytic follicular thyroid cells

Answer 31

Medullary thyroid carcinoma
Parathyroid tissue

Question 32

PAX8::GLIS1 fusions

Answer 32

Hyalinized trabecular tumor of the thyroid

Question 33

Erysipelas

Answer 33

A bacterial infection of the skin’s outer layers.
Compared to cellulitis, another type of skin infection, erysipelas affects more surface layers of skin.

Question 34

Formal names of gastric signet ring cell carcinoma

Answer 34

poorly cohesive carcinoma by the World Health Organization (WHO)
classification or diffuse-type gastric adenocarcinoma by the Laurén classification.

Question 35

Environmental risk factors for gastric
carcinoma

Answer 35

Environmental risk factors for gastric carcinoma include Helicobacter pylori infection, tobacco smoking, radiation, and exposure to rubber manufacturing.

Question 36

Hereditary diffuse gastric cancer (HDGC).

Answer 36

CDH1 (encoding E-cadherin) germline mutation is the most common pathologic mutation in HDGC. The average age of onset of PCC in these patients is 38 years (range: 14-69 years). Other genetic abnormalities implicated in HDGC are germline mutations in CTNNA1, PALB2, BRCA2, and MAP3K6.

Question 37

Hereditary diffuse gastric cancer (HDGC).

Answer 37

CDH1 (encoding E-cadherin) germline mutation is the most common pathologic mutation in HDGC. The average age of onset of PCC in these patients is 38 years (range: 14-69 years). Other genetic abnormalities implicated in HDGC are germline mutations in CTNNA1, PALB2, BRCA2, and MAP3K6.

Question 38

Other names for Poorly cohesive gastric carcinomas

Answer 38

Poorly cohesive carcinoma (PCC) is also known as linitis plastica, or poorly differentiated adenocarcinoma, and can be either signet-ring cell type or non-signet-ring cell type. Signet ring cell carcinoma (SRCC) is composed predominantly or exclusively of signet-ring cells, which are characterized by a central, optically clear, globoid droplet of cytoplasmic mucin with an eccentrically placed nucleus. Non-signet-ring cell subtypes include tumors composed of neoplastic cells resembling inflammatory cells such as lymphocytes, histiocytes, or plasma cells with deeply eosinophilic cytoplasm, or neoplastic cells with bizarre nuclei.

Question 39

National Comprehensive Cancer Network (NCCN) 2022 guidelines recommend universal testing for gastic carcinoma

Answer 39

MSI in all newly diagnosed patients. HER2 IHC or FISH/ISH and PD-L1 IHC are also recommended at the time of diagnosis if metastatic disease is documented or suspected, as trastuzumab can be used in treatment of HER2 (ERBB2)-amplified tumors.

Question 40

molecular gastric carcinoma subtypes by The Cancer Genome
Atlas

Answer 40

Question 41

Joint mice versus rice bodies

Answer 41

Any free-floating tissue aggregates within a joint space may be referred to as loose bodies (or joint mice). Osteochondral loose bodies typically occur in patients with osteoarthritis, with the knee being the most common location. Of note, while osteochondral loose bodies can occur in osteoarthritis, fibroinflammatory loose bodies (known as rice bodies) can occur in rheumatoid arthritis.

Question 42

Young patients with osteochondral loose bodies may have what disease?

Answer 42

osteochondritis dissecans, an idiopathic condition wherein bone around a joint partially or fully breaks off, likely due to decreased blood flow

Question 43

Chondromyxoid fibroma

Answer 43

Chondromyxoid fibroma usually arises in male patients in the second or third decade of life, with a predilection for the knee area (proximal tibia / distal femur). Imaging shows a lobulated, well-circumscribed lytic lesion with a sclerotic margin within the metaphysis. Microscopically, it consists of nodules of bland stellate cells embedded in a myxoid matrix with a surrounding dense fibrous stroma. Occasional osteoclast-like giant cells are often encountered. Focal calcification or hyaline cartilage may be seen, but bone formation should not be present. Immunohistochemical findings are nonspecific, though chondromyxoid fibroma can show a number of GRM1 recombinations.

Question 44

second most common primary skeletal malignancy

Answer 44

Chondrosarcoma, usually occurring in patients aged 20 to 50. The distal femur is a common site, but chondrosarcoma should not be expected to exist predominantly within a joint space. Central chondrosarcomas can arise from enchondromas. Secondary
chondrosarcomas can also arise within osteochondromas of long bones, pelvis, or shoulder blade. Low-grade chondrosarcomas may show mild atypia, but highergrade cases show hypercellularity, moderate atypia, prominent nucleoli, and visible mitotic activity. The chondroid matrix is often myxoid. Bone should not be seen as a
true component of chondrosarcoma, though native bone may be entrapped within an infiltrative lesion. IDH1 and IDH2 mutations have been described in approximately 50% of central chondrosarcomas.

Question 45

most common primary skeletal malignancy

Answer 45

Osteosarcoma. The distal femur is the most common site, and most cases occur in teenagers, though there is a second peak (roughly one third of cases) after age 40. While several subtypes exist, a common unifying histologic feature is atypical tumor cells producing immature lacelike osteoid material (so-called “malignant osteoid”). A number of genetic mutations have been described in osteosarcoma; affected genes include MYC, MDM2, FGFR1, and CDKN2A. Secondary osteosarcoma can arise in numerous settings, including bone infarcts, Paget disease, and in an osteochondral loose body.

Question 46

Clear cell sarcoma of soft tissue is

Answer 46

Clear cell sarcoma of soft tissue is a rare aggressive malignant soft tissue neoplasm that predominantly affects adolescents and young adults. They commonly affect the deep soft tissue in the extremities, close to tendons and aponeuroses. They are composed of monotonous epithelioid and spindle cells and are characterized by EWSR1::ATF1 or EWSR1::CREB1 gene fusions and melanocytic
differentiation. By immunohistochemistry, clear cell sarcoma expresses S100 protein, SOX10, Melan-A, and HMB45.

Question 47

Mesothelioma express IHC markers and loss of what?

Answer 47

Mesothelioma express classic mesothelial immunohistochemical markers such as calretinin, D2-40, WT1, and CK5/6. BAP1 immunohistochemistry shows loss of nuclear staining in more than 50% of cases

Question 48

Perivascular epithelioid cell tumor (PEComa)

Answer 48

Perivascular epithelioid cell tumor (PEComa) is a group of soft tissue tumors that include angiomyolipoma, epithelioid angiomyolipoma, and lymphangioleiomyomatosis. A subset of patients with this tumor may have tuberous sclerosis complex. PEComa can affect any organ and usually present as painless masses. Women are more frequently affected than men. PEComa are composed of epithelioid cells with abundant eosinophilic granular or clear cytoplasm arranged in a
nested growth pattern. Tumor nuclei are round with small nucleoli. PEComa are positive for both melanocytic markers, like HMB45, and myogenic markers such as SMA or desmin. The most common genetic abnormalities include TSC2 mutations and TFE3 fusions.

Question 49

What is the most important prognostic factor for leiomyosarcoma in assessing clinical behavior?

Answer 49

Leiomyosarcoma are aggressive neoplasms, and in terms of clinical behavior, site alone is one of the most important prognostic factors. Indeed, retroperitoneal leiomyosarcoma are prone to both local recurrence and metastasis because of their location, while cutaneous leiomyosarcoma (atypical intradermal smooth muscle neoplasms) are associated with an excellent prognosis. Metastases to the lung, liver, soft tissue, and occasionally skin can occur.

Question 50

Angiosarcoma IHC

Answer 50

positive for CD31, ERG, CD34, and FLI1.

Question 51

Epithelioid sarcoma

Answer 51

Epithelioid sarcoma is a rare soft tissue sarcoma occurring in pediatric and adult populations, composed of epithelioid cells with an epithelial phenotype. It clinically presents as single or multiple painless, slow-growing ulcerated nodules on the hands, fingers, and forearm. Histologically, it is composed of cellular nodules of
epithelioid cells with central necrosis. The neoplastic cells are positive for low- and high-molecular-weight cytokeratins, EMA, and CD34. The majority of cases show a loss of INI1 protein by immunohistochemistry and INI1 (SMARCB1) biallelic deletions
by FISH analysis.

Question 52

Hashimoto thyroiditis (HT)

Answer 52

CLT may be associated with the clinical presentation of Hashimoto thyroiditis (HT), which is an autoimmune thyroiditis that results from autoantibodies to thyroid-specific antigens (most commonly antimicrosomal and antithyroglobulin antibodies) leading to
the destruction of follicular epithelial cells. Approximately 5% of the population has HT, and it is considered one of the most common autoimmune diseases. HT can present as the classic type or fibrous subtype, with the classic type affecting a wide age range and the fibrous subtype being more common in older male patients.

Question 53

most common cause of a painful thyroid?

Answer 53

Subacute thyroiditis (or de Quervain thyroiditis) is the most common cause of a painful thyroid and is an inflammatory condition characterized by the presence of multinucleated giant cells, acute inflammatory cells, and epithelioid histiocytes, typically following a viral infection. Subacute thyroiditis will lack the three components
seen in CLT (lymphocytes, germinal centers, and oncocytic follicular cells).

Question 54

Krukenberg tumors

Answer 54

Signet ring cell carcinoma metastases to the ovary
are known as Krukenberg tumors.

Question 55

Immunohistochemistry and/or molecular profiles can provide supportive data to help determine the primary GI site.

Answer 55

Appendiceal tumors demonstrate a similar immunoprofile to colorectal adenocarcinomas but will also retain expression of
SMAD4 more frequently than other GI tumors. Pancreaticobiliary tumors often express CK7 and CK20 but are negative for SATB2, and more than half show loss of SMAD4 expression. Gastric tumors can variably express CK7 and/or CK20, are often negative for SATB2, and often retain expression of SMAD4. Colon adenocarcinoma
with ovarian metastasis have a high frequency of KRAS, SMAD4 (DPC4), and NTRK1 mutations compared to those without ovarian metastasis. While SATB2 is expressed in the majority of colorectal carcinomas, loss of SATB2 expression is associated with DNA mismatch repair protein deficiency and BRAF V600E mutations.

Question 56

Mucinous carcinoma (MC) of the ovary IHV

Answer 56

Typically, ovarian MC are
positive for CK7 and CA19-9 and variably positive for CK20, CDX2, and CEA. MC are typically negative for WT1, Napsin A, vimentin, ER, and PR. Rare primary ovarian tumors arising from teratomas are negative for CK7, with expression of CK20 only. A subset of tumors show aberrant p53 expression, and p16 is typically negative or focally positive (non-block-type). SATB2 positivity can be seen in mucinous tumors associated with mature teratomas.

Question 57

Metastatic adenocarcinoma, HPV-independent, gastric type, of uterine cervix IHC pattern

Answer 57

By immunohistochemistry, gastric-type endocervical adenocarcinomas are typically positive for PAX8 and CK7, often
express CK20 and CDX2, and are negative for ER, PR, p16 (non-block-like), and SATB2.

Question 58

Loss of SATB2 expression in colorectal adenocarcinoma is associated with which of the following?

Answer 58

While SATB2 is expressed in the majority of colorectal carcinomas, loss of SATB2 expression is associated with DNA mismatch
repair protein deficiency and BRAF V600E mutations.

Question 59

Diffuse expression of which of the following stains most supports a diagnosis of low-grade endometrial stromal sarcoma (LG-ESS)?

Answer 59

IFITM1 is an interferon-induced transmembrane
protein that is downstream of the Wnt/beta-catenin signaling pathway and is typically diffusely expressed in low-grade endometrial stromal sarcomas and not expressed in uterine smooth muscle tumors. BCOR and cyclin D1 are commonly expressed in
high-grade endometrial stromal sarcomas. While low-grade endometrial stromal sarcomas can show focal desmin or inhibin expression if they have smooth muscle or sex cord-like differentiation, respectively, these markers should not be diffusely
expressed within the tumor cells.

Question 60

Which of the following can distinguish LG-ESS from an endometrial stromal nodule?

Answer 60

Low-grade endometrial stromal sarcomas often have
lymphovascular invasion, but endometrial stromal nodules do not. Both entities have diffuse CD10 expression and can have the JAZF1::SUZ12 gene fusion. Endometrial stromal nodules are well-circumscribed but can have small tumor protrusions (typically fewer than 3) as long as they are <3 mm.

Question 61

Which of the following tumors morphologically mimics a myxoid
leiomyosarcoma?
a) Cellular leiomyoma
b) High-grade ESS with YWHAE::NUTM2 fusion
c) High-grade ESS with ZC3H7B::BCOR fusion
d) LG-ESS with JAZF1::SUZ12 fusion
e) NTRK-rearranged spindle cell neoplasm

Answer 61

C): High-grade ESS with a ZC3H7B::BCOR fusion are infiltrative spindle cell tumors with a myxoid matrix, thus closely resembling myxoid leiomyosarcoma. In contrast to myxoid leiomyosarcoma, they express cyclin D1 and BCOR and lack expression of SMA, desmin, and h-caldesmon.

Question 62

the most common type of placental neoplasm

Answer 62

Chorangiomas. Large chorangiomas (>4 cm) may be associated with intrauterine growth restriction (IUGR), arterio-venous shunting, and fetal cardiac failure. Chorangiomas express GLUT1, similarly to infantile hemangiomas, and may occur concurrently.

Question 63

Define chorangiosis

Answer 63

Chorangiosis is a placental vascular lesion defined microscopically as at least 10 low power fields containing at least 10 terminal villi, each with at least 10 capillaries (the rule of 10s). This diagnosis is reserved for term placentas (≥37 weeks). Grossly, these placentas are often large for gestational age. On low power, the terminal villi
appear larger than expected for gestational age due to the increase in villous capillaries. Vascular congestion may mimic chorangiosis. Chorangiosis is much more common than chorangiomas and affects 5%-10% of placentas. In contrast to chorangioma and chorangiomatosis, vascular pericytes are not present. Chorangiosis, like chorangioma, is thought to develop as an adaptive response to
placental underperfusion/hypoxia. Risk factors include maternal anemia, preeclampsia, diabetes, smoking, pregnancy at high elevations, and fetal cardiac anomalies. Chorangiosis has been associated with poor fetal outcome, increased rate of cesarean delivery, IUGR, and stillbirth.

Question 64

Beckwith–Wiedemann syndrome

Answer 64

Results from imbalancebof paternal and maternal alleles at 11p15.5. Grossly, the placentas are large for gestational age with cystic degeneration. Hemorrhagic and gelatinous areas are common and simulate chorangioma, especially on ultrasound. Microscopically, the placentas have enlarged stem villi with cysts and normal terminal villi. Stem villi may also show stromal and vascular proliferation. Features of fetal vascular malperfusion, including stem vessel obliteration, avascular villi, and chorangiomatosis, are often present.

Question 65

What genetic syndrome is most commonly associated with an increased risk of urothelial carcinoma of the renal pelvis?

Answer 65

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common cause of hereditary colorectal
cancer. Lynch syndrome also leads to an increased risk for uterine, stomach, liver, kidney (including urothelial carcinoma of renal pelvis), and certain types of skin cancers.

Question 66

Which of the following is the only known risk factor for development of Xp11 translocation RCC?
a) History of chemotherapy
b) History of renal failure
c) History of sickle cell disease
d) History of tuberous sclerosis
e) Pediatric age group

Answer 66

A. Prior chemotherapy is the only known risk factor for developing an Xp11 translocation RCC. Translocation RCC are not exclusive to pediatric patients and young age is not considered a risk factor for development. Tuberous sclerosis does impart an increased risk for developing RCC but not transcription RCC, while renal failure has no known impact on this risk. Sickle cell disease is associated with renal medullary carcinomas.

Question 67

Hypertrophic osteoarthropathy (HOA)

Answer 67

a medical condition characterized by abnormal proliferation of skin and periosteal tissues involving the extremities and characterized by three clinical features: digital clubbing (also termed Hippocratic fingers), periostosis of tubular bones, and synovial effusions. HOA can be a primary entity, known as pachydermoperiostosis, or can be secondary to extraskeletal conditions, with different prognoses and management implications for each. There is a high association between secondary HOA and malignancy, especially non–small cell lung cancer. In such cases, it can be considered a form of paraneoplastic syndrome.

Question 68

pachydermoperiostos

Answer 68

Primary HOA

Question 69

three clinical features of HOA

Question 70

Angiomyolipoma

Answer 70

The most common benign mesenchymal renal neoplasm.
A male-female ratio of 1:4.
Sporadic (80% of cases) or syndromic, occurring in tuberous sclerosis complex (TSC) patients.
Activation of the mammalian target of rapamycin (mTOR) pathway.
The presence of synchronous or metachronous involvement of
other sites, including lymph nodes, is regarded as multicentric disease rather than
metastasis.

Question 71

tuberous sclerosis complex (TSC)

Answer 71

autosomal dominant multisystem disorder.
subependymal giant cell astrocytoma, cerebral cortical dysplasia, cutaneous shagreen patches, angiofibroma, and subungual fibroma. TSC is associated with genetic alterations in the tuberous sclerosis genes TSC1 and TSC2.

Question 72

perivascular epithelioid cell-related mesenchymal
neoplasms (PEComa)

Answer 72

Angiomyolipoma, lymphangioleiomyomatosis, clear cell ”sugar” tumor of the lung, hepatic falciform ligament clear cell myomelanocytic tumor, and cardiac rhabdomyomas.

Question 73

Myelolipoma

Answer 73

Myelolipoma typically involves the adrenal gland, and on imaging may present as a renal mass, although rare cases have been reported in the kidney. They are composed of benign trilineage myeloid and mature lipomatous components, often with increased megakaryocytes. They are believed to arise from metaplastic change in the mesenchymal cells due to various factors including inflammation, stimulation by erythropoietin and adrenocorticotrophic hormones, and t(3;21)(q25;p11)
translocation. Dystrophic vessels and expression of melanocytic markers are not seen.

Question 74

Which gene is involved in the characteristic translocation seen in the cellular variant of CMN? Congenital mesoblastic nephroma.

Answer 74

Cellular CMN is characterized by translocation t(12;15)(p13;q25) that results in ETV6::NTRK3 fusion found in approximately 70% of cases.

Question 75

pulmonary alveolar proteinosis (PAP).

Answer 75

PAP is a rare disease in which surfactant components accumulate in the alveoli and impair gas exchange. There are three types of PAP. The most frequent form, primary PAP, includes autoimmune PAP (formerly known as idiopathic PAP), which accounts for more than 90% of all PAP. Secondary PAP is mainly due to inhaling toxic substances (discussed below), while congenital PAP accounts for approximately 2% of PAP and is caused by disorders of surfactant production, causing severe hypoxia in neonates.

Question 76

Autoimmune pulmonary alveolar proteinosis

Answer 76

Autoimmune PAP is a disease of adults, with a median age of 39, but it has been reported in all ages. It occurs in both men and women, though men are more commonly affected and most patients are smokers. In normal lung, extra surfactant is cleared by alveolar macrophages; however, in PAP, surfactant accumulates because of defective macrophage function, caused in most cases by a neutralizing autoantibody to GM-CSF. Anti-GM-CSF antibody is elevated in most patients with autoimmune PAP, but this is not required for diagnosis. Additionally, patients may
have telomerase gene mutations.

Question 77

Pulmonary chondroma (PC)

Answer 77

PC is a benign cartilaginous tumor of the lung. It most often presents as a component of Carney triad (CT), a rare non-hereditary, multiple endocrine neoplasia tumor predisposition syndrome. Whether or not PC occurs outside of the syndrome is controversial. The initial description of CT included PC, gastrointestinal stromal tumors (GIST), and paragangliomas. Subsequently, esophageal leiomyoma and adrenal cortical adenoma were added. CT has a predilection for young women with an average age of 18. Patients with CT often develop multiple multifocal tumors, usually PC or GIST, which can be either synchronous or metachronous. Identification of a GIST or a chondroma, especially in a young female, should lead to further investigation to rule out CT.

Question 78

Carney triad (CT)

Answer 78

Carney triad (CT), a rare non-hereditary, multiple endocrine neoplasia tumor predisposition syndrome. Whether or not PC occurs outside of the syndrome is controversial. The initial description of CT included PC, gastrointestinal stromal tumors (GIST), and paragangliomas. Subsequently, esophageal leiomyoma and adrenal cortical adenoma were added. CT has a predilection for young women with an average age of 18. Patients with CT often develop multiple multifocal tumors, usually PC or GIST, which can be either synchronous or metachronous. Identification of a GIST or a chondroma, especially in a young female, should lead to further investigation to rule out CT.

Question 79

Carney triad tumors

Answer 79

Carney triad tumors belongs to the group of tumors classified as succinate dehydrogenase (SDH)-deficient tumors as they are characterized by loss of function of the SDH complex. The SDH complex is a mitochondrial enzyme complex composed of four protein subunits (A, B, C, and D). Dysregulation of any of these protein subunits leads to functional deficiency of the entire SDH complex. This can arise by germline or somatic mutations in individual subunits or, as in CT, by an epigenetic mechanism: post-zygotic systemic hypermethylation of succinate dehydrogenase promoter locus in subunit C. As loss of any component of the complex leads to functional deficiency of the entire complex, loss of immunohistochemical staining for succinate dehydrogenase B (SDHB) can be used as a surrogate marker for identification of SDH-deficient tumors. Loss of staining with SDHB may also be useful in separating PC from its histologic mimics such as pulmonary hamartoma. When loss of staining is found in tumors associated with CT, additional studies should be done to evaluate for underlying CT.

Question 80

most common tumors in CT Carney triad

Answer 80

The most common tumors in CT are GIST, chondromas, and paragangliomas. Esophageal leiomyoma and adrenal
cortical adenoma have also been described

Question 81

solid pseudopapillary neoplasm (SPN) of the pancreas

Answer 81

These tumors most commonly occur in young women with a mean age of 28 years, typically occurring as a solitary body or tail lesion.
Exhibit nuclear beta-catenin expression, which is very specific, although they may also be positive for CD10. Also, cyclin D1, CD99
(dot-like pattern), and progesterone receptor are helpful positive stains. Amongst these markers, nuclear beta-catenin positivity is most specific to SPN.
CTNNB1 mutations in exon 3 are a hallmark of SPN, seen in more than 90% of tumors. This mutation leads to activation of the Wnt signaling pathway and subsequent activation of various genes, particularly CCND1.
Low-grade malignant neoplasms and generally have a good prognosis. The 10-year disease-specific survival rate is 96%, even for patients with metastatic disease. However, there are reports of more aggressively malignant SPN in cases that demonstrate sarcomatoid features, high mitotic rate, vascular and/or perineural invasion, larger size, male sex, necrosis, and invasion of peripancreatic structures.

Question 82

Mucinous cystic neoplasm (MCN) of the pancreas

Answer 82

preferential occurrence in women and in the pancreatic tail. This differential diagnosis arises primarily at imaging, as histologically the tumors have little overlap. MCN is cystic and lined by mucinous epithelium. MCN also has characteristic ovarian-type stroma that will stain positive with CD10, estrogen receptor, and inhibin. However, the epithelial cells are negative for these markers and positive for cytokeratins 7, 8,18, and 19 and CEA.