APPROACH TO UNDIFFERENTIATED
TUMORS
by
Dr. Varughese George
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Approach to undifferentiated tumors
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APPROACH TO UNDIFFERENTIATED
TUMORS
by Dr. Varughese George
Introduction
“Undifferentiated” tumors
- (^) Tumors lacking evidence of lineage differentiation on the basis of routine light microscopic morphology.
- (^) Tumors mimicked by different types of tumors causing diagnostic challenge
- (^) Tumors that require an algorithmic diagnostic approach elucidating its true nature crucial for clinical management.
GENERAL APPROACH FOR UNDIFFERENTIATED TUMORS Categorize malignant tumors according to morphologic appearances. Undifferentiated tumors can be categorized according to morphologic appearances into 4 major groups:
Tumors according to morphologic appearances
1. Small round cell
tumors
Heterogeneous groups of
tumors composed of
relatively small, round
to oval, closely packed
undifferentiated cells,
high nuclear to
cytoplasmic ratio,
scant cytoplasm, round
nuclei
Desmoplastic small round cell tumor The tumor cells appear monotonous and undifferentiated and are small to intermediate sized, round or polygonal, with small hyperchromatic nuclei, inconspicuous nucleoli and scant cytoplasm. Brisk mitotic activity
Tumors according to morphologic appearances
2. Epithelioid cell
tumors
Tumors have large
round-oval to
polygonal shape with
a nesting/sheeting
arrangement Photomicrograph of
undifferentiated carcinomatous tumor composed of epithelioid cells with nesting arrangement and a desmoplastic stroma separating tumor cell nests (hematoxylin-eosin,
Epithelioid cell tumors Differential Diagnosis
- (^) Rhabdomyoma
- (^) Granular cell tumor
- (^) Epithelioid sarcoma
- (^) Epithelioid variants
of leiomyosarcoma
- (^) Epithelioid variant of
malignant
peripheral nerve
sheath tumor
- (^) Angiosarcoma
- (^) Epithelioid
hemangioendotheliom
a
- (^) Malignant extrarenal
rhabdoid tumor
- (^) Pleomorphic
rhabdomyosarcoma
- (^) Clear cell sarcoma
- (^) Alveolar soft part
sarcoma
- (^) Metastatic tumors
Spindle Cell Tumors Differential Diagnosis Muscle
- (^) Leiomyoma.
- (^) Leiomyosarcoma.
- (^) Rhabdomyosarcoma. Nerve sheath
- (^) Neurofibroma.
- (^) Malignant Peripheral Nerve Sheath Tumor. Vascular - (^) Angiosarcoma - (^) Kaposi’s sarcoma Myofibroblastic - (^) Fibromatosis - (^) Nodular Fascitis - (^) Inflammatory Myofibroblastic Tumor
Spindle Cell Tumors Differential Diagnosis Fibrohistiocytic
- (^) Dermatofibroma
- (^) Dermatofibrosarcom a protuberans
- (^) Malignant Fibrous Histiocytoma Adipose
- (^) Dedifferentiated liposarcoma Non-sarcomas - (^) Spindle cell carcinoma - (^) Spindle cell melanoma Others - (^) Gastrointestinal Stromal Tumors - (^) Solitary fibrous tumor - (^) Hemangiopericytoma - (^) Synovial Sarcoma
Pleomorphic tumors Differential Diagnosis Skin:
- (^) Benign fibrous histiocytoma
- (^) Carcinoma
- (^) Melanoma
- (^) Atypical fibroxanthoma Limbs:
- (^) Unclassified pleomorphic sarcomas (“Malignant Fibrous Histiocytoma”)
- (^) High-grade myxofibrosarcoma
- (^) Leiomyosarcoma
- (^) Liposarcoma (pleomorphic or dedifferentiated)
- (^) Rhabdomyosarcoma
Extremities:
- (^) Giant cell tumor of
tendon sheath
Retroperitoneum
- (^) Dedifferentiated
liposarcoma
- (^) Leiomyosarcoma
General approach for undifferentiated tumors Determine a main lineage of differentiation.
- (^) Morphologic clues such as a specific
growth pattern and nuclear or cytoplasmic
characteristics can guide to a diagnosis in
some cases of undifferentiated tumors.
Epithelial tumors
- (^) Poorly differentiated comprises ≈ 15% to
20% of carcinomas.
- (^) Cytokeratin stains are excellent marker of
epithelial differentiation strongly &
diffusely expressed in carcinomas.
- (^) Diagnosis of carcinoma must be seriously
evaluated when an epithelioid tumor is
overwhelmingly positive for pankeratin
stains.
Melanocytic tumors
- (^) A diffuse strong staining with S100 , CK (-) in undifferentiated tumor is good for a melanoma.
- (^) S100 is not specific for melanoma as it is also expressed by some carcinomas & sarcomas.
- (^) Unusual variants ( de-differentiated liposarcoma / mesenchymal chondrosarcoma / malignant peripheral nerve sheath tumor ) may pose a challenge to distinguish from melanoma.
- (^) Requires confirmation by additional melanoma markers such as HMB-45 , Melan A , tyrosinase , or NKI/C.
Mesenchymal tumors
- (^) Strong vimentin expression in a non-melanocytic, non-lymphoid neoplasm is generally an indication of being a sarcoma.
- (^) Sarcomas may have
- (^) small round blue-cell tumor morphology (Ewing’s sarcoma)
- (^) spindle and epithelioid cells (synovial sarcoma)
- (^) pure epithelioid cells (epithelioid sarcoma)
- (^) Not all sarcomas are negative for epithelial markers.
- (^) Epithelioid sarcoma & synovial sarcoma shows strong staining for epithelial markers.
General approach for undifferentiated tumors Specify a diagnosis.
- (^) Once the main lineage of tumor differentiation is determined, one can proceed to make a much more specific diagnosis.
- (^) In this step, clinical correlation as well as additional ancillary studies is needed.