Effusions: Mesothelioma and Metastatic Cancers

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1 Effusions: Mesothelioma and Metastatic Cancers

2 Malignant Mesothelioma Incidence: 2,500 cases/year ~60-80% pts with pleural MM relationship with asbestos exposure Other risk factors: radiation, other carcinogens, potentially SV40 virus (simian vacuolating virus - under investigation) 50% one year survival ~50% of pts with peritoneal MM have asbestosis

3 Malignant Mesothelioma Present with recurrent pleural effusions, chest pain and dyspnea Males usually 6 th 8 th decade Diagnosis: Clinical history + imaging finding + cytology/biopsy

4 Malignant Mesothelioma Effusion color and consistency of honey Epithelial type (50-70% of cases) numerous large clusters large cells, prominent nuclei, abundant dense cytoplasm with pale rim cell block - solid masses occasionally vacuolated, psammoma bodies Other types: fibrosarcomatous (7-20%) and mixed

5 Malignant mesothelioma - cellular specimen with variety of groupings

6 Malignant mesothelioma

7 Mesothelioma

8 Mesothelioma - wall to wall mesothelial cells; single and in groups

9 Mesothelioma - two toned/stained glass appearance of cytoplasm and scalloping of group borders

10 Mesothelioma - large abnormal nuclei with prominent nucleoli

11 Malignant Mesothelioma (Ancillary and Histochemical Studies) Hyaluronic acid levels in effusion samples Histochemistry PAS and Alcian blue stain glycogen (and mucin) in mesothelial cells and adenocarcinoma Diastase after PAS and hyaluronidase after Alcian blue will be negative in mesotheliomas (glyocen is digested)

12 Malignant Mesothelioma (Ancillary Studies) Immunocytochemistry most commonly used Mesothelial markers Calretinin cytokeratin 5/6 HBME-1 WT-1 D2-40 Mesothelin Podoplanin

13 Malignant Mesothelioma Poor prognosis Treatment: Surgery most effective Chemotherapy and/or radiotherapy (localized recurrence)

14 Site ology Adenocarcinoma cells are the most common type of neoplastic cells to be found in serous fluids

15 Identification of the presence of a monomorphic or dimorphic population of cells

16 Adenocarcinomas - Breast Classification infiltrating ductal carcinoma papillary medullary mucinous lobular

17 Breast Breast cancer cells cannon balls/proliferation spheres may present as a monomorphic effusion pattern may closely resemble mesothelial cells

18 Metastatic breast carcinoma - proliferative sphere

19 Cell block from metastatic breast ca can see gland formation

20 Cells showing mucin positivity in metastatic breast cancer

21 Ascites - mesothelial pattern of breast cancer - monomorphic population - but of cancer cells

22 Linear arrangement of metastatic breast ca

23 Metastatic breast ca - cell within a cell arrangement

24 Immunostains for determination of breast primary Estrogen (ER) Progesterone (PR) Her-2 neu GCDFP-15 (Gross cystic disease firbrillary protein formerly known as BRST-2) Mammaglobin

25 Pulmonary Primaries Adenocarcinoma most common Small cell carcinoma SCC - rare

26 Adenocarcinoma

27 Adenocarcinoma lung primary

28 Small Cell Carcinoma vertebral column arrangement of cells spherical cells in cluster formations - lack of cytoplasm cell block can be contributory

29 Small cell carcinoma - single file arrangement

30 SCLC can cluster and round up in fluids key is lack of cytoplasm

31 Molded clusters may be small and easy to overlook.

32 Ascites >500 ml of fluid in peritoneum portal venous hypertension, hypoproteinemia, aldosterone excess, neoplasm ovary, breast, stomach, pancreas, liver, colon, lymphoreticular, mesothelioma

33 Ovarian Carcinoma Classification serous and mucinous papillary cystadenocarcinoma endometrioid Arrangements single cells and diplocellular groups small clusters papillary fragments - predominant pattern proliferative spheres (w/wo soap bubbles ) rosettes

34 Soap bubbles commonly seen in ovarian carcinoma

35 Ovarian adenocarcinoma

36 Ovarian carcinoma - papillary groups with psammoma bodies

37 Psammoma body seen in metastatic endometrial carcinoma

38 Pseudomyxoma Peritonei Diffuse intra-abdominal mucinous tumor ( jelly belly ) Very rare disease No genetic or environmental causes known at this time Average age in 5 th and 6 th decades Etiologies/primaries Appendiceal most common Ovarian borderline tumors, carcinomas Colonic carcinomas

39 Pseudomyxoma Peritonei Two main categories Acellular or rare benign adenoma cells = disseminated peritoneal adenomucinosis Low grade mucinous adenocarcinomas = peritoneal mucinous carinomatosis Dr. John H. Donohue Cancer Connection presentation 8/9/07

40 Pseudomyxoma Peritonei Indolent growth slow accumulation of mucin Often more than 5 years before clinically evident Eventually can fill entire abdomen Rare lymphatic spread even in adenocarcinomas

41 Pseudomyxoma Peritonei Cytology Mucin and rare cells Adenoma cells appear benign Adenocarcinomas usually low grade so may also be fairly bland

42

43 GIT Malignancy Often lose their characteristic columnar form and occur as 3D clusters or as papillary clusters

44 Ascites - 3D fragment from GI tumor

45 Gastric cancer can present as single cells similar to mesothelial cells.

46 Gastric cancer

47 Signet ring gastric cancer in pleural fluid

48 Columnar forms from rectosigmoid ca

49 Lymphoma Effusion is a common complication The most common cause of a chylous effusion is lymphoma

50 Pleural fluid CLL

51 lymphoma leukemia

52 Abnormal mitotic figure in large cell lymphoma

53 Burkitt s lymphoma

54 Which side has the lymphoma?

55 Melanoma Obviously malignant cells single cell dispersion may be amelanotic

56 Melanoma - nuclear hole Intranuclear inclusion of melanoma

57 Melanoma - S100 positivity Immunostain S100

58 Melanoma pigment. Bi-nucleation is also common

59 Melanoma mulitnucleation and clusters

60 Squamous Cell Carcinoma rarely sheds diagnostic cells in effusion non keratinizing squamous cell more common than keratinizing primary neoplasm of lung, female genital tract or larynx

61 Single atypical cell from metastatic squamous cell carcinoma

62 Cell block from metastatic SCC - elongate forms and pyknotic nuclei

63 Conclusions 1. Beware of diagnosing malignancy in the presence of degenerated cells 2. Reactive mesothelial cells and histiocytes can mimic carcinoma

64 Conclusions con t 3. Clinical information is the single most useful feature in determining the primary site of a tumor 4. Not all effusions in patients with cancer are malignant

65 Immunocytochemistry for identification of metastases Adenocarcinoma markers mcea MOC-31 CD15 B72.3 Ber-EP4 Melanoma: HMB45, S100, Mart-1, MelanA Hematopoietic: LCA, L26, CD38 Others: TTF-1, PSA and PAP

66 An Example: Mesothelioma vs Adenocarcinoma WT-1 D2-40

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