Skip to main content
Close

Case 13

View the images and select the correct diagnosis from the list below.

The Great Pretender

This is a pleural fluid specimen from an 86-year-old male. There was a remote history of moderately differentiated prostatic adenocarcinoma:

Image 1 

Image 2 

Image 3 CK5/6 

Image 4 Calretinin 

Image 5 TTF-1 

Select one of the following:

You answered: Epithelioid mesothelioma 


CORRECT!!


CYTOPATHOLOGY:

  • Malignant cells look like mesothelial cells (no foreign or distinct second population of cells), cytologically ranging from benign-appearing to frankly malignant
  • Important clue at low power - "more and bigger cells in more and bigger clusters" (aggregates containing 30-200 or more cells are characteristic)
  • Cell clusters are highly irregular, knobby, with flower-like or papillary outlines, and are three-dimensional, with numerous "cell-in-cell" or "cell-embracing" patterns
  • Individual cells are usually larger and more variable than benign mesothelial cells; giant multinucleated forms are often seen. Cells, however, maintain a relatively constant N/C ratio, which imparts a certain degree of uniformity, and resemblance to benign mesothelial cells (kinship). Spindle cells may be seen
  • Peripheral cytoplasmic blebs and microvilli (lacy skirts) are accentuated in malignant mesothelial cells. Cytoplasmic vacuolation may also be seen
  • Nuclei are centrally or paracentrally located, with enlarged, multiple, irregular mucleoli. Macronucleoli are associated with malignancy. Mitotic figures are NOT helpful unless they are atypical, which is rarely seen

DISCUSSION:

  • Malignant mesothelioma is a tumour related to asbestos exposure
  • It arises most commonly in the pleura, and less commonly in the peritoneum (tumours in the pericardium or tunica vaginalis of the testis are rare)
  • Cells grow as multiple plaques that coalesce into larger nodules visible radiographically as a pleural thickening
  • Classified as:
    • epithelioid (most common; shows tubular, papillary, microcystic +/- patterns);
    • sarcomatoid; or
    • mixed (biphasic) types
  • The majority of patients present with an effusion, usually unilateral, that is characteristically viscous to gelatinous (like synovial fluid, or honey) due to elevated levels of hyaluronic acid
  • There are several diagnostic challenges: 

    • Hard to distinguish from reactive mesothelial cells: 

      Reactive mesothelial cells are usually less abundant, and form smaller, less complex groups or flat sheets. Nuclei are more monomorphic, and may contain small nucleoli.

      Mesothelioma cells are usually extremely abundant, and form large, irregular, complex three-dimensional aggregates. Nuclei are pleomorphic, with multiple or macronucleoli.

      Flow cytometry (to measure DNA content) and cytogenetics may be used to aid distinction. Mesotheliomas show clonal cytogenetic aberrations (deletions of 1p, 3p, 22q are most common) - detected by fluorescence-in-situ hybridization (FISH) on liquid-based preparations
    • Hard to distinguish from metastatic adenocarcinoma, particularly when cells have vacuolated cytoplasm

      Adenocarcinoma has two distinct cell populations: PAS-D positive, negative for calretinin, CK5/6, WT1 (with exception of ovarian), positive for CEA, Leu-M1, B72.3, BER-EP4, TTF-1 (if from lung). Microvilli show a small length:diameter ratio on electron microscopy.

      Mesothelioma has a morphologic continuum with benign-appearing mesothelial cells; PAS-D negative, positive for calretinin, CK5/6, WT1 (with exception of ovarian), negative for CEA, Leu-M1, B72.3, BER-EP4, TTF-1. Microvilli show a length:diamter ratio of 15:1 or greater on electron microscopy
    • Epithelioid hemangioendothelioma is a good mimic of mesotheliomas (aggregates with round, centrally placed nuclei, abundant cytoplasm); positive for vascular markers CD34 and CD31, negative for calretinin and WT1

BACK TO IMAGES


HISTOLOGY


REFERENCES:

DeMay RM. The Art & Science of Cytopathology. Chicago: ASCP Press, 1996; 278-85.

Cibas ES. Cytology: Diagnostic Principles and Clinical Correlates, Second Edition. Saunders, 2003; 126

 

You answered: Reactive mesothelial hyperplasia 
Sorry, that is INCORRECT

The correct diagnosis is: Epithelioid Mesothelioma

CYTOPATHOLOGY:

  • Malignant cells look like mesothelial cells (no foreign or distinct second population of cells), cytologically ranging from benign-appearing to frankly malignant
  • Important clue at low power - "more and bigger cells in more and bigger clusters" (aggregates containing 30-200 or more cells are characteristic)
  • Cell clusters are highly irregular, knobby, with flower-like or papillary outlines, and are three-dimensional, with numerous "cell-in-cell" or "cell-embracing" patterns
  • Individual cells are usually larger and more variable than benign mesothelial cells; giant multinucleated forms are often seen. Cells, however, maintain a relatively constant N/C ratio, which imparts a certain degree of uniformity, and resemblance to benign mesothelial cells (kinship). Spindle cells may be seen
  • Peripheral cytoplasmic blebs and microvilli (lacy skirts) are accentuated in malignant mesothelial cells. Cytoplasmic vacuolation may also be seen
  • Nuclei are centrally or paracentrally located, with enlarged, multiple, irregular mucleoli. Macronucleoli are associated with malignancy. Mitotic figures are NOT helpful unless they are atypical, which is rarely seen

DISCUSSION:

  • Malignant mesothelioma is a tumour related to asbestos exposure
  • It arises most commonly in the pleura, and less commonly in the peritoneum (tumours in the pericardium or tunica vaginalis of the testis are rare)
  • Cells grow as multiple plaques that coalesce into larger nodules visible radiographically as a pleural thickening
  • Classified as:
    • epithelioid (most common; shows tubular, papillary, microcystic +/- patterns);
    • sarcomatoid; or
    • mixed (biphasic) types
  • The majority of patients present with an effusion, usually unilateral, that is characteristically viscous to gelatinous (like synovial fluid, or honey) due to elevated levels of hyaluronic acid
  • There are several diagnostic challenges: 

    • Hard to distinguish from reactive mesothelial cells: 

      Reactive mesothelial cells are usually less abundant, and form smaller, less complex groups or flat sheets. Nuclei are more monomorphic, and may contain small nucleoli.

      Mesothelioma cells are usually extremely abundant, and form large, irregular, complex three-dimensional aggregates. Nuclei are pleomorphic, with multiple or macronucleoli.

      Flow cytometry (to measure DNA content) and cytogenetics may be used to aid distinction. Mesotheliomas show clonal cytogenetic aberrations (deletions of 1p, 3p, 22q are most common) - detected by fluorescence-in-situ hybridization (FISH) on liquid-based preparations
    • Hard to distinguish from metastatic adenocarcinoma, particularly when cells have vacuolated cytoplasm

      Adenocarcinoma has two distinct cell populations: PAS-D positive, negative for calretinin, CK5/6, WT1 (with exception of ovarian), positive for CEA, Leu-M1, B72.3, BER-EP4, TTF-1 (if from lung). Microvilli show a small length:diameter ratio on electron microscopy.

      Mesothelioma has a morphologic continuum with benign-appearing mesothelial cells; PAS-D negative, positive for calretinin, CK5/6, WT1 (with exception of ovarian), negative for CEA, Leu-M1, B72.3, BER-EP4, TTF-1. Microvilli show a length:diamter ratio of 15:1 or greater on electron microscopy
    • Epithelioid hemangioendothelioma is a good mimic of mesotheliomas (aggregates with round, centrally placed nuclei, abundant cytoplasm); positive for vascular markers CD34 and CD31, negative for calretinin and WT1

BACK TO IMAGES


HISTOLOGY


REFERENCES:

DeMay RM. The Art & Science of Cytopathology. Chicago: ASCP Press, 1996; 278-85.

Cibas ES. Cytology: Diagnostic Principles and Clinical Correlates, Second Edition. Saunders, 2003; 126

 

You answered: Metastatic adenocarcinoma
 Sorry, that is INCORRECT 

The correct diagnosis is: Epithelioid Mesothelioma

CYTOPATHOLOGY:

  • Malignant cells look like mesothelial cells (no foreign or distinct second population of cells), cytologically ranging from benign-appearing to frankly malignant
  • Important clue at low power - "more and bigger cells in more and bigger clusters" (aggregates containing 30-200 or more cells are characteristic)
  • Cell clusters are highly irregular, knobby, with flower-like or papillary outlines, and are three-dimensional, with numerous "cell-in-cell" or "cell-embracing" patterns
  • Individual cells are usually larger and more variable than benign mesothelial cells; giant multinucleated forms are often seen. Cells, however, maintain a relatively constant N/C ratio, which imparts a certain degree of uniformity, and resemblance to benign mesothelial cells (kinship). Spindle cells may be seen
  • Peripheral cytoplasmic blebs and microvilli (lacy skirts) are accentuated in malignant mesothelial cells. Cytoplasmic vacuolation may also be seen
  • Nuclei are centrally or paracentrally located, with enlarged, multiple, irregular mucleoli. Macronucleoli are associated with malignancy. Mitotic figures are NOT helpful unless they are atypical, which are rarely seen

DISCUSSION:

  • Malignant mesothelioma is a tumour related to asbestos exposure
  • It arises most commonly in the pleura, less commonly in peritoneum (tumours in pericardium or tunica vaginalis of the testis are rare)
  • Cells grow as multiple plaques that coalesce into larger nodules visible radiographically as a pleural thickening
  • Classified as:
    • epithelioid (most common; shows tubular, papillary, microcystic +/- patterns);
    • sarcomatoid; or
    • mixed (biphasic) types
  • The majority of patients present with an effusion, usually unilateral, that is characteristically viscous to gelatinous (like synovial fluid, or honey) due to elevated levels of hyaluronic acid
  • There are several diagnostic challenges:
    • Hard to distinguish from reactive mesothelial cells.

      Reactive mesothelial cells are usually less abundant, and form smaller, less complex groups or flat sheets. Nuclei are more monomorphic, and may contain small nucleoli.

      Mesothelioma cells are usually extremely abundant, and form large, irregular, complex three-dimensional aggregates. Nuclei are pleomorphic, with multiple or macronucleoli.

      Flow Cytometry (to measure DNA content) and cytogenetics may be used to aid distinction. Mesotheliomas show clonal cytogenetic aberrations (deletions of 1p, 3p, 22q most common) - detected by fluorescence-in-situ hybridization (FISH) on liquid-based preparations
    • Hard to distinguish from metastatic adenocarcinoma, particularly when cells have vacuolated cytoplasm

      Adenocarcinoma has two distinct cell populations; PAS-D positive, negative for calretinin, CK5/6, WT1 (with exception of ovarian), positive for CEA, Leu-M1, B72.3, BER-EP4, TTF-1 (if from lung). Microvilli show small length:diameter ratio on electron microscopy.

      Mesothelioma has a morphologic continuum with benign-appearing mesothelial cells; PAS-D negative, positive for calretinin, CK5/6, WT1 (with exception of ovarian), negative for CEA, Leu-M1, B72.3, BER-EP4, TTF-1. Microvilli show length:diamter ratio of 15:1 or greater on electron microscopy.
    • Epithelioid hemangioendothelioma is a good mimic of mesotheliomas (aggregates with round, centrally placed nuclei, abundant cytoplasm); positive for vascular markers CD34 and CD31, negative for calretinin and WT1.

BACK TO IMAGES

                      

HISTOLOGY


REFERENCES:

DeMay RM. The Art & Science of Cytopathology. Chicago: ASCP Press, 1996; 278-85.

Cibas ES. Cytology: Diagnostic Principles and Clinical Correlates, Second Edition. Saunders, 2003; 126-30.

You answered: Epithelioid hemangioendothelioma
Sorry, that is INCORRECT

The correct diagnosis is: Epithelioid Mesothelioma

CYTOPATHOLOGY:

  • Malignant cells look like mesothelial cells (no foreign or distinct second population of cells), cytologically ranging from benign-appearing to frankly malignant
  • Important clue at low power - "more and bigger cells in more and bigger clusters" (aggregates containing 30-200 or more cells are characteristic)
  • Cell clusters are highly irregular, knobby, with flower-like or papillary outlines, and are three-dimensional, with numerous "cell-in-cell" or "cell-embracing" patterns
  • Individual cells are usually larger and more variable than benign mesothelial cells; giant multinucleated forms are often seen. Cells, however, maintain a relatively constant N/C ratio, which imparts a certain degree of uniformity, and resemblance to benign mesothelial cells (kinship). Spindle cells may be seen
  • Peripheral cytoplasmic blebs and microvilli (lacy skirts) are accentuated in malignant mesothelial cells. Cytoplasmic vacuolation may also be seen
  • Nuclei are centrally or paracentrally located, with enlarged, multiple, irregular mucleoli
  • Macronucleoli are associated with malignancy. Mitotic figures are NOT helpful unless they are atypical, which are rarely seen

DISCUSSION:

  • Malignant mesothelioma is a tumour related to asbestos exposure
  • It arises most commonly in the pleura, less commonly in peritoneum (tumours in pericardium or tunica vaginalis of the testis are rare)
  • Cells grow as multiple plaques that coalesce into larger nodules visible radiographically as a pleural thickening
  • Classified as:
    • epithelioid (most common; shows tubular, papillary, microcystic +/- patterns);
    • sarcomatoid; or
    • mixed (biphasic) types
  • The majority of patients present with an effusion, usually unilateral, that is characteristically viscous to gelatinous (like synovial fluid, or honey) due to elevated levels of hyaluronic acid
  • There are several diagnostic challenges: 

    • Hard to distinguish from reactive mesothelial cells.

      Reactive mesothelial cells are usually less abundant, form smaller, less complex groups or flat sheets. Nuclei are more monomorphic, and may contain small nucleoli.

      Mesothelioma cells are usually extremely abundant, and form large, irregular, complex three-dimensional aggregates. Nuclei are pleomorphic, with multiple or macronucleoli.

      Flow cytometry (to measure DNA content) and cytogenetics may be used to aid distinction. Mesotheliomas show clonal cytogenetic aberrations (deletions of 1p, 3p, 22q most common) - detected by fluorescence-in-situ hybridization (FISH) on liquid-based preparations

    • Hard to distinguish from metastatic adenocarcinoma, particularly when cells have vacuolated cytoplasm.

      Adenocarcinoma has two distinct cell populations; PAS-D positive, negative for calretinin, CK5/6, WT1 (with exception of ovarian), positive for CEA, Leu-M1, B72.3, BER-EP4, TTF-1 (if from lung). Microvilli show small length:diameter ratio on electron microscopy.

      Mesothelioma has a morphologic continuum with benign-appearing mesothelial cells; PAS-D negative, positive for calretinin, CK5/6, WT1 (with exception of ovarian), negative for CEA, Leu-M1, B72.3, BER-EP4, TTF-1. Microvilli show length:diamter ratio of 15:1 or greater on electron microscopy

    • Epithelioid hemangioendothelioma is a good mimic of mesotheliomas (aggregates with round, centrally placed nuclei, abundant cytoplasm); positive for vascular markers CD34 and CD31, negative for calretinin and WT1

BACK TO IMAGES


HISTOLOGY


REFERENCES:

DeMay RM. The Art & Science of Cytopathology. Chicago: ASCP Press, 1996; 278-85.

Cibas ES. Cytology: Diagnostic Principles and Clinical Correlates, Second Edition. Saunders, 2003; 126-30.

 

From the Cytopathology files of BC Cancer
Submitted by: Carol Lee, MD and Tom Thomson, MD

SOURCE: Case 13 ( )
Page printed: . Unofficial document if printed. Please refer to SOURCE for latest information.

Copyright © BC Cancer Agency. All Rights Reserved.

    Copyright © 2017 Provincial Health Services Authority