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Approach to undifferentiated tumors, Slides of Pathology

Approach to undifferentiated tumors

Typology: Slides

2018/2019

Uploaded on 04/10/2019

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APPROACH TO UNDIFFERENTIATED
TUMORS
by
Dr. Varughese George
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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.