Soft Tissue - Epithelioid, Round Cell and Pleomorphic Pattern Flashcards
Epithelioid Pattern
- Tumour cells are polygonl or rounded with moderate amounts of cytoplasm
Types:
* Epithelioid haemangioma
* Epithelioid sarcoma
* Epithelioid haemangioendothelioma
* PEComas
* Glomus tumour
* Alveolar soft part sarcoma
Associated features to note in the architecture:
* LOBULATED: epithelioid haemangioma
* NESTED: PEComas, Alveolar soft part sarcoma
* CLEAR CELL: PEComas
* PROMINENT BLOOD VESSELS: Glomus tumour, Epithelioid haemangioma
Glomus tumor
- Mesenchymal tumor composed of modified smooth muscle cells that arise from the glomus body
- Sucquet-Hoyer canal of the glomus body –> a specialized arteriovenous anastomosis that regulates heat in the skin and is surrounded by layers of epithelioid, SMA+ glomus cells
- WHO –> benign pericytic tumour
- Benign tumors cured by complete surgical excision; recurrence rate of 10% likely due to incomplete resection
- Painful
- Described throughout the body; most common is upper extremity (62%), particularly the fingers (27%)
- Subungual region is the most common location on the finger
- Outside extremities, GIT (particularly stomach) is most common location
Micro:
* Well circumscribed mass composed of 3 components: glomus cells, vasculature and smooth muscle cells
* Solid glomus tumor (75% of cases): predominantly glomus cells, poor vasculature and rare smooth muscle cells
* Branching capillary sized vessels lined by endothelial cells surrounded by collars of uniform glomus cells forming nests, sheets and trabeculae in a hyalinized or myxoid stroma
* Glomus cell has a round shape with indistinct borders with a rounded, sharply punched out nucleus in an amphophilic to eosinophilic cytoplasm
* Chromatin is homogenous and bland with inconspicuous nucleoli
* Very rare mitoses
Molecular:
* MIR143-NOTCH gene fusions in more than half of benign and malignant glomus tumors; can be evaluated by FISH
IHC:
Vimentin (100%)
smooth muscle actin (99%)
muscle specific actin (95%
calponin (80%)
CD34 (32 - 53%; typically focal) (
Collagen type IV
Laminin (91%; pericellular)
h-caldesmon
Epithelioid sarcoma
- A malignant mesenchymal neoplasm that exhibits epithelioid cytomorphology and a predominantly epithelial phenotype
- Unpredictable clinical course
- Better prognosis in pediatric patients
Micro:
Two typical morphologies:
* Classic/Distal type with epithelioid to spindled cells with central pseudogranulomatous architecture
* Proximal type with predominant epithelioid and rhabdoid cells
Prognosis:
* Classic type more common than proximal type
* Proximal type has worse prognosis
Molecular:
* High frequency of SMARCB1 (INI1) deletion (22q11)
IHC:
Pancytokeratin, CAM 5.2, EMA (nearly all cases)
Vimentin
CD34 (50%)
ERG (40%)
CA-125 –> for monitoring
Loss of INI1
Epithelioid hemangioendothelioma
- Endothelial neoplasm that most commonly involves soft tissue, bone, lung, skin and liver
- Locally aggressive tumor with metastatic potential
- Indolent course compaired to angiosarcoma
- recurs locally
Micro:
* Usually minimal mitotic activity, atypia or necrosis
* Up to 10% of cases exhibit frank malignant features of prominent nuclear pleomorphism, increased mitotic activity, solid growth or necrosis; these tumors resemble epithelioid angiosarcoma and have a more aggressive behavior
WWTR1-CAMTA1 subtype (classic EHE):
* Cords, strands or small nests of large endothelial cells with abundant eosinophilic cytoplasm embedded in a myxohyaline stroma
* Tumor cells have vesicular, round to oval, sometimes indented nuclei
* Some tumor cells have intracytoplasmic, round, clear vacuoles representing small vascular lumina, which may contain erythrocytes
YAP-TFE3 subtype:
* Solid nests or pseudo alveolar arrangement of epithelioid cells enmeshed in a fibrous stroma
* Tumor cells have abundant, densely eosinophilic cytoplasm and can form vascular spaces
* Intracytoplasmic vacuoles are rare
Molecular:
* Defined by recurrent WWTR1-CAMTA1 or YAP1-TFE3 gene fusion
Translocations result in:
* Fusion of CAMTA1 on 1p36.23 to WWTR1 on 3q25.1
* Fusion of exon 1 of YAP1 and exon 4 of TFE3
IHC:
ERG
CD31
CD34 (can be negative)
podoplanin (D2-40)
FLI1
von Willebrand factor
CAMTA1 in WWTR1-CAMTA1 rearranged tumors
TFE3 in YAP-TFE3 rearranged (less specific)
Clear cell sarcoma of soft tissue
- Young adult, M:F = 1, distal extremity, slow growing
- Not related to epidermis (hence, tendon and aponeuroses)\
- Do not confuse with clear cell sarcoma of kidney
- Foot and ankle > hand > thigh > trunk > head & neck
- 75% distal extremities
Micro:
* Essential: nests of epithelioid spindle cells with clear eosinophilic cytoplasm and prominent nucleoli plus melanocytic differentiation
* Vaguely organoid (neuroendocrine-like) pattern: nests and short fascicles of epithelioid or spindle cells, surrounded by a delicate framework of fibrocollagenous tissue contiguous with the adjacent tendons and aponeurosis
* Scattered Touton type or wreath-like multinucleated giant cells are relatively common
* Necrosis usually focally in 33%
* Melanin pigment in scattered cells in half of the cases
* No involvement of epidermis or no epidermal melanocytic proliferation but longstanding lesions (especially at fingers) may enlarge and therefore tumors may ulcerate
Molecular:
* t(12;22)(q13;q12) for EWSR1-ATF1 in 90 - 95%
* t(2;22)(q32.3;q12) for EWSR1(ex7)-CREB1(ex7) in 5 - 10% –> commonly GI tract clear cell sarcoma
IHC:
S100 (100%),
SOX10 (95%)
HMB45 (97%, patchy or focal)
MITF (81%)
MelanA (71%)
BCL2 (93%)
CD57 (75%)
Alveolar soft part sarcoma
- Alveolar soft part sarcoma (ASPS) is a rare sarcoma of uncertain histogenesis
- Most commonly seen in patients aged 15 - 35 years; 72% were < 30 years
- Female predominance
- Commonly involves deep soft tissues of the extremities (61%; predominantly the lower extremity [51%]), trunk (20%), internal organs (8%) and head and neck (9%)
- In adults, deep soft tissue of the thigh and buttock is common
- In children, there is a predilection for the head and neck region, especially the tongue and orbit
- At presentation, the tumor can be localized (38%), regional (11%) and metastatic (43%)
- Long term follow up is mandatory given risk of mets >10 years after diagnosis.
Micro:
* Organoid and nest-like growth pattern
* Central discohesion results in characteristic pseudoalveolar-like structures
* Lobules of tumor are divided by thick fibrous septa and rich capillary vascular network
* Dilated veins usually present at the periphery of the mass
* Vascular invasion is common
Molecular:
* t(X;17)(p11;q25) that results in the fusion of the TFE3 transcription factor gene (from Xp11) with ASPSCR1 at 17q25.3
IHC:
TFE3 demonstrates nuclear immunoreactivity
Cathepsin K is typically positive
PAS highlights intracytoplasmic crystals and granules (PAS positive / diastase resistant)
MCT1 and CD147 are positive in intracytoplasmic granules
Rhabdomyoma
- Benign tumor of mature skeletal muscle
- Extracardiac rhabdomyomas are divided into fetal, adult and genital histologic types
- Extracardiac tumors are not associated with tuberous sclerosis
- Some cases may be due to degeneration / regeneration and not be neoplastic
- Very rare
- Usually head and neck, particularly oral cavity
Micro:
* Well circumscribed, not encapsulated
* Sheets of large, well differentiated skeletal muscle cells
* Cells are round or polygonal with abundant eosinophilic fibrillar or granular cytoplasm with frequent cross striations and intracytoplasmic rod-like inclusions
* Nuclei are small, round and vesicular, may have prominent nucleoli
* May have spider cells with vacuolated cytoplasm (cells resemble spider webs)
* No mitotic activity, no atypia
IHC:
* PTAH and Masson trichrome highlight cross striations and rod like inclusions
* MSA
* Desmin
* Myoglobin
Embryonal Rhabdomyosarcoma
- Embryonal rhabdomyosarcoma (ERMS) is the most common RMS subtype
- Several distinct and prognostic patterns of growth have been noted, including the botryoid and anaplastic variants
- Spindle cell type
- Botryoid type
- Botryoid embryonal rhabdomyosarcoma (sarcoma botryoides) only occurs in certain locations, specifically beneath mucosal epithelial lined viscera, such as the bladder, biliary tract, vagina or upper respiratory tract, extrahepatic bile ducts or near a space; rarely in eyelid or anal region
- Often has a grape-like (botryoid) growth pattern
- 25% of rhabdomyosarcomas, 10% of embryonal subtype
Syndromes:
Costello syndrome (HRAS)
neurofibromatosis type 1 (NF1)
Noonan syndrome (PTPN11 and others)
Beckwith-Wiedemann syndrome (changes to 11p15)
Dicer syndrome (DICER1)
Li-Fraumeni syndrome (TP53)
Gorlin syndrome (PTCH1)
Diagnostic Criteria:
* Round and spindle cell morphology with scattered differentiated rhabdomyoblasts
* Desmin positivity and heterogenous nuclear staining for myogenin or MYOD1
* Lack of FOXO1 gene rearrangements distinguished poorlyt differentiated ERMS from solid alveolar RMS
IHC:
Desmin (diffuse positive)
Myogenin (scattered cells positive)
MyoD1 (scattered cells positive)
Alveolar Rhabdomyosarcoma
- Highly aggressive type of rhabdomyosarcoma characterized by uniform, primitive, round cells showing skeletal muscle differentiation
- Affects adolescents and young adults
- Peak incidence is between 10 and 25 years
- Commonly involves deep soft tissue of extremities, typically forearm
- Other sites include head and neck, trunk, paraspinal, pelvic, genitourinary regions and retroperitoneum
- Can present with widespread involvement, such as bone marrow infiltration (leukemia-like presentation) and lymphadenopathy
Micro:
* Cellular round cell tumor
* Large clusters, nests, cords and trabeculae of primitive round cells, separated by variably thick fibrovascular septa
* Loss of cellular cohesion in the center forms alveolar-like, cystic and vague papillary appearance
* Multinucleated tumor giant cells with wreath-like lineup of nuclei are common
* Brisk mitoses
* Necrosis
Molecular:
* PAX3::FOXO1 fusion has a poorer outcome than PAX7::FOXO1 fusion
IHC:
Desmin (cytoplasmic and membranous)
Myogenin (strong and diffuse nuclear)
MyoD1 (scattered cells positive)
Desmoplastic small round cell tumor
- A malignant mesenchymal neoplasm composed of small round tumor cells associated with prominent stromal desmoplasia
- Uncertain histiogenesis
- Mostly males
- Vast majority of patients develop tumors in the abdominal cavity
- Multiple serosal implants are common
- Clinical presentation outside the abdominal cavity is rare and mainly restricted to the thoracic cavity and paratesticular region
- Despite multimodal treatment, DSRCT is associated with dismal outcomes
Micro:
* Well defined nests of small round cells separated by desmoplastic stroma
* In the more desmoplastic areas, tumor cells may be arranged as thin trabeculae or in a single file fashion
* Uniform cells with small hyperchromatic nuclei, inconspicuous nucleoli, scant cytoplasm and indistinct cytoplasmic borders
* Peripheral palisading is common
* Rosette-like structures and pseudopapillae may be observed
* Central necrosis is common
* Cystic degeneration can be seen
Molecular:
* EWSR1-WT1 break apart FISH demonstrates separation of signals indicative of translocation involving the EWS locus
* t(11,22)
IHC:
WT1 (C terminus)
Desmin (distinct dot-like and perinuclear cytoplasmic staining pattern)
Keratin (a distinctive dot-like cytoplasmic expression is seen occasionally)
EMA
Vimentin (a distinctive dot-like cytoplasmic expression is seen occasionally)
GFAP
neurofilament protein
synaptophysin
NSE
AR and KIT expression in 37% and 35% of DSRCTs, respectively
Atypical fibroxanthoma
- Rare low grade malignant cutaneous tumor of uncertain differentiation
- Low grade malignant cutaneous neoplasm
- Low grade tumor with an almost always benign clinical course
- Recurrence may occur due to incomplete surgical removal
- Metastasis is rare
- Slight male predominance
- Usually presents on the sun exposed skin (e.g. head and neck) of elderly patients
- Rarely, young patients with Li-Fraumeni syndrome or xeroderma pigmentosum
- Radiotherapy, immunosuppression, UV radiation
Micro:
* Dermal based, well circumscribed tumor
* Composed of irregularly arranged spindled to epithelioid cells with no involvement of the subcutis
* Necrosis, lymphovascular invasion and perineural invasion should not be present
* Cytomorphologically, lesional cells are highly bizarre and atypical, with marked pleomorphism in size and shape, abundant eosinophilic cytoplasm, occasional multinucleation and numerous mitotic figures, including atypical forms
* Epidermal collarette, ulceration and actinic changes, including prominent solar elastosis, may be present
* No connection to the overlying epidermis and no in situ component
Molecular:
* FAT1, NOTCH1/2, CDKN2A, TP53, TERT mutations
IHC:
Nonspecific: CD10, CD99, procollagen 1, vimentin
