Effusions: Mesothelioma and Metastatic Cancers
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
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
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
Malignant mesothelioma - cellular specimen with variety of groupings
Malignant mesothelioma
Mesothelioma
Mesothelioma - wall to wall mesothelial cells; single and in groups
Mesothelioma - two toned/stained glass appearance of cytoplasm and scalloping of group borders
Mesothelioma - large abnormal nuclei with prominent nucleoli
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)
Malignant Mesothelioma (Ancillary Studies) Immunocytochemistry most commonly used Mesothelial markers Calretinin cytokeratin 5/6 HBME-1 WT-1 D2-40 Mesothelin Podoplanin
Malignant Mesothelioma Poor prognosis Treatment: Surgery most effective Chemotherapy and/or radiotherapy (localized recurrence)
Site ology Adenocarcinoma cells are the most common type of neoplastic cells to be found in serous fluids
Identification of the presence of a monomorphic or dimorphic population of cells
Adenocarcinomas - Breast Classification infiltrating ductal carcinoma papillary medullary mucinous lobular
Breast Breast cancer cells cannon balls/proliferation spheres may present as a monomorphic effusion pattern may closely resemble mesothelial cells
Metastatic breast carcinoma - proliferative sphere
Cell block from metastatic breast ca can see gland formation
Cells showing mucin positivity in metastatic breast cancer
Ascites - mesothelial pattern of breast cancer - monomorphic population - but of cancer cells
Linear arrangement of metastatic breast ca
Metastatic breast ca - cell within a cell arrangement
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
Pulmonary Primaries Adenocarcinoma most common Small cell carcinoma SCC - rare
Adenocarcinoma
Adenocarcinoma lung primary
Small Cell Carcinoma vertebral column arrangement of cells spherical cells in cluster formations - lack of cytoplasm cell block can be contributory
Small cell carcinoma - single file arrangement
SCLC can cluster and round up in fluids key is lack of cytoplasm
Molded clusters may be small and easy to overlook.
Ascites >500 ml of fluid in peritoneum portal venous hypertension, hypoproteinemia, aldosterone excess, neoplasm ovary, breast, stomach, pancreas, liver, colon, lymphoreticular, mesothelioma
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
Soap bubbles commonly seen in ovarian carcinoma
Ovarian adenocarcinoma
Ovarian carcinoma - papillary groups with psammoma bodies
Psammoma body seen in metastatic endometrial carcinoma
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
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
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
Pseudomyxoma Peritonei Cytology Mucin and rare cells Adenoma cells appear benign Adenocarcinomas usually low grade so may also be fairly bland
GIT Malignancy Often lose their characteristic columnar form and occur as 3D clusters or as papillary clusters
Ascites - 3D fragment from GI tumor
Gastric cancer can present as single cells similar to mesothelial cells.
Gastric cancer
Signet ring gastric cancer in pleural fluid
Columnar forms from rectosigmoid ca
Lymphoma Effusion is a common complication The most common cause of a chylous effusion is lymphoma
Pleural fluid CLL
lymphoma leukemia
Abnormal mitotic figure in large cell lymphoma
Burkitt s lymphoma
Which side has the lymphoma?
Melanoma Obviously malignant cells single cell dispersion may be amelanotic
Melanoma - nuclear hole Intranuclear inclusion of melanoma
Melanoma - S100 positivity Immunostain S100
Melanoma pigment. Bi-nucleation is also common
Melanoma mulitnucleation and clusters
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
Single atypical cell from metastatic squamous cell carcinoma
Cell block from metastatic SCC - elongate forms and pyknotic nuclei
Conclusions 1. Beware of diagnosing malignancy in the presence of degenerated cells 2. Reactive mesothelial cells and histiocytes can mimic carcinoma
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
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
An Example: Mesothelioma vs Adenocarcinoma WT-1 D2-40