Cytopathology of metastatic neoplasiaDr. Akshay AgarwalModerator: Dr. Hoogar M. B.

Overview Metastatic neoplasia in lymph node Metastatic neoplasia in lung Diagnosis of primary and secondary

lymphomatous effusions

Lymph node metastasis FNAC Imprint cytology Frozen

Microacinar patternProstate, NEC, Thyroid

MucinousBreast, ovary, pancreas

Papillary patternThyroid, ovary, breast

Breast carcinoma Diffuse infiltration involves airways Better differentiated tumors may be

recognized by its cohesive clusters of small glandular cells, with relatively uniform nuclei and a smooth border to the cell group

Nuclei may be moulded but have a more regular chromatin pattern and better defined nuclear membranes than oat cell carcinoma cells

Presence of intracytoplasmic mucin vacuoles favours a breast origin

For poorly differentiated tumors ER/PR S100 CEA

Colorectal carcinoma Palisaded columnar cells with oval

nuclei and apical mucin secretion Cytoplasmic border of the cell group

tends to be linear Cavitatory necrosis

Renal Cell Carcinoma Predeliction for infiltrating mucosal

surfaces. Pleomorphic malignant cells with round

eccentric nuclei, prominent nucleoli and abundant finely vacuolated cytoplasm

Eosinophilic basement membrane material

Fibrovascular papillary cores

Melanoma Free cell pattern Pleomorphic nuclei with prominent

nucleoli, presence of duble nuclei and spindle cell forms

Melanin may or may not be seen Irregular blue-green on MGG And Brown on PAP

Lymphoma NHL, most likely high grade follicular

lymphoma N:C ratio high, narrow blue rim of

cytoplasm with prominent nucleoli HL, lobulated nuclei with macronucleoli,

associated with eosinophils, histiocytes and lymphocytes

Sarcoma Pleomorphic malignant cells with

spindle cell forms, giant cells and vascular cell sheets

Basic First Line IHC Panel for Detection of Primary Site in Metastasis

mimics Pleomorphic adenoma

Submandibular LN Atypia in epithelial cells

Warthin’s Tumor Lymphoid cells Necrotic debris and epithelial cells

Hashimoto’s Thyroiditis Reactive lymphoid cells Bizarre cytology with hurthle cells

Benign epithelial inclusions Degenerative atypia in branchial cysts

Lung Metastasis Some organs such as the lungs and the

lymph nodes are more commonly affected by metastases than by primary neoplasia and so knowledge of advances is important.

Cytology of metastatic neoplasia in the lung Brushings or sputum Wider range is accessible with FNAC Breast and colorectal carcinomas Prostatic, renal, bladder and head and

neck carcinoma As well as melanoma, lymphoma,

testicular tumours and sarcomas

The diagnosis of metastasis can usually be established by a combination of the cytological appearance, clinical history and pattern of metastasis

IHC may be helpful, but requires cell blocks.

Patterns of spread

Cannon-ball / miliary Colorectal Renal Melanoma Sarcoma Ovarian Medullary carcinoma – thyroid

Diffuse parenchymal infiltration

Lymphangitic Lung and breast carcinoma, lymphoma

Intravascular GIT, liver, Choriocarcinoma

Lepidic Well differentiated AdenoCa of prostate

and pancreas

Mimics of lung cancer

Solitary Renal and colorectal carcinoma,

melanoma, sarcoma Endobronchial

Renal and colorectal carcinoma, sarcoma

Cytological patterns suggestive metastasis High index of suspicion when malignant

cells do not conform to the usual spectrum of appearances in lung cancer.

Final diagnosis always requires clinicopathological correlation and ancillary tests.

Diagnosis of 1o and 2o lymphomatous effusions Majority are secondary Can occur in NHL T/B cell type HL Late manifestation of systemic

lymphomas Pleural fluid in the setting of a

mediastinal or pulmonary mass

Primary Lymphomatous Effusions Lymphomas presenting as primary

pleural effusions are rare. Most are

DLBCL Follicular Lymphoma Small lymphocytic lymphoma

Majority are B cell Phenotype Pleural thickening with mediastinal

lymphadenopathy

Body cavity based NHL that occurs exclusively in HIV positive patients

Pleural / pericardial / peritoneal in the absence of solid tumor masses.

Throughout remain confined to the body cavity.

Morphologically, Large cell Immunoblastic Anaplastic

Abundant amphophilic or basophilic cytoplasm, bizarre cells with irregular nuclei and RS like cells

EBV and HHV-8 associated Diagnosis based on IHC

CD30, CD38, EMA positive Associated with castleman’s syndrome Extremely poor prognosis 2-4 months survival

PEL can be distinguished from secondary body cavity lymphomas by:1. Almost exclusive involvement of body

cavity2. Pleomorphic morphology3. IHC4. HHV-8

Pyothorax-associated Lymphoma Rare lymphomas, occur in setting of long-

standing inflammation of the pleura Underlying cause of chronic inflammation

such as TB, IL-6 associated 20-50 years after initial pleural injury Exclusively in the pleura Not associated with Immunosuppression

Morphology resemble PEL, Immunoblastic Anaplastic Bizarre cells

Do not express pan-B cell markers EBV positive

Conclusion Identification of metastatic diseases in

crucial to upstage the tumor Preliminary diagnosis should follow

thorough search of primary site IHC is mandatory for confirmation and

typing Detailed history should be available