Case 33 - Discussion

Uploaded: 2007-03-16, Updated: 2007-06-22

IMMUNOHISTOCHEMISTRY:
Immunostains of the solid tumor: beta-catenin weakly positive, CK AE1/AE3 negative, CK5/6 negative, CK8/18 negative, MUC-1 uncontributable. CK7 focally positive, CK20 focally positive, MUC1 positive, P53 focally weakly positive, CD68 the osteoclast-like giant cells strongly positive, Desmin negative, CD10 negative, MUC-1 uncontributible.Special staining PAS/H and PAS/D-LG are negative
Immunostains of the solid tumor:: The lining epithelium of the cyst wall shows strong positivity for MUC-1, CA19-9, EMA, CK19, CK8/18 and CK7. The epithelium also shows focal positivity for CEA. The stroma of the cystic neoplasm is strongly positive for CD10.

ELECTRON MICROSCOPY:
Ultrastructurally, the tumor consists of large neoplastic cells with variable sizes and shapes. The tumor cells have abundant cytoplasm with moderate amount endoplasmic reticulum and some mitochondria. There is no predominance of any specific organelles in the cytoplasm. In focal areas, the tumor cells have single round nuclei, but majority of the tumor cells have large irregular nuclei. Multinucleated giant cells are present. The nucleoli are inconspicuous. (Interpretation performed by Dr. Z. Pan. Performed in the Electron Microscopy Laboratory, Creighton Medical Laboratories, Omaha, NE.)

CYTOGENETICS REPORT (performed at University of Nebraska Medical Center Human Genetics Laboratory, Omaha, NE, report on file):
Normal female chromosome complement.
Cytogenetic analysis did not reveal any evidence of a consistent detectable numerical or structural chromosomal anomaly at this band level.
NOMENCLATURE: 46,XX[20]

DIAGNOSIS

SPLEEN AND PARTIAL PANCREAS, RESECTION:
- Anaplastic carcinoma of pancreas, maximal tumor dimension 8.0 cm.
   a. The anaplastic carcinoma is predominantly composed of poorly differentiated spindle cells.
   b. Necrosis, osteoclast-like giant cell reaction and squamoid differentiation are present.
- Mucinous cystadenocarcinoma, moderately to poorly differentiated, maximal dimension of the cyst 4.0 cm.
- All surgical margins are free of malignancy and anterior margin shows a microscopic pancreatic intraepithelial neoplasm (PanIN IA).
- Seven lymph nodes are free of malignancy.
- Sections of spleen are unremarkable.
- Permanent sections confirm frozen diagnosis.
- Histopathological staging AJCC PT2 PN0 PMX stage Ib.

Anaplastic Carcinoma of Pancreas

Clinical Futures

• Other terms: pleomorphic carcinomas, pleomorphic giant cell carcinomas, spindle cell carcinomas, sarcomatoid carcinomas, and undifferentiated carcinoma;

• Frequency: 2-7%;

• More frequent in the body and tail than in the head;

• M > F.

Gross Findings

• Average size, 6 cm;

• Cystic changes with necrosis;

Microscopic Findings

• Pleomorphic large cells and spindle cells in poorly cohesive, sarcomatoid formations with desmoplastic response;

• Tumor cells are bizarre, mononuclear or multinucleated giant cells with eosinophilic cytoplasm;

• Cell cannibalism/tumor phagocytosis: engulfment of red blood cells or other tumor cells;

• Osteoclast-like giant cells;

• High mitotic rates with frequent perineural, lymphatic and blood vessel invasion;

• Foci of glandular differentiation or squamous differentiation;

• Tumor necrosis.

Subtypes

• Spindle cell type/carcinosarcoma /sarcomatoid carcinoma: Mean survival 6 months. Predominantly spindle cells dominate with occasional giant and bizarre cells, or biphasic with epithelial/glandular and sarcomatoid components. Heterologous differentiation (cartilage, bone, striated muscle) may be present;

• Osteoclastic giant cell type: better prognosis. contain 5 cellular components: osteoclast-like giant cells, pleomorphic large cells, histiocyte-like mononuclear cells, atypical mononuclear cells (nucleus resembles pleomorphic large cells), ductal carcinoma cells: Osteoclast-like giant cells: CD68+, keratin negative, no Kras mutation; non-neoplastic; Pleomorphic large cells (not always present): CD68-, often have Kras mutations: Histiocyte-like mononuclear cells: CD68+, keratin+, often have Kras mutations; Atypical mononuclear cells: CD68-, often have Kras mutations; Ductal carcinoma cells: CD68-, same Kras mutations as pleomorphic large cells and mononuclear cells. Molecular: osteoclast-like giant cells lack Kras mutations, but mononuclear cells have similar Kras mutations as ductal carcinoma cells

• Pleomorphic giant cell type: mono- and multinucleated pleomorphic giant cells; pleomorphic tumor with discohesive, bizarre, multinucleated giant cells (not osteoclast-like); resembles giant cell carcinomas of lung, adrenal, liver; dense inflammatory infiltrate with emperipolesis (neutrophils in tumor cells). EMA and keratin positive

• Round cell anaplastic type: small, round, and uniform cells, intermingled with occasional eosinophilic plump cells and giant cells.

Differential Diagnosis

• Melanoma: S100+, HMB45+;

• Pleomorphic rhabdomyosarcoma: desmin and actin +;

• Pleomorphic sarcoma: vimentin +, cytokeratin -;

• Metastatic carcinoma

• Choriocarcinoma: HCG+

• Anaplastic large cell lymphoma

• Epithelioid sarcomas

• Malignant fibrous histiocytoma

Immunohistochemistry Straining

• CK7+, pancytokeratin+

• Glandular component CEA+

• Osteoclastic-like giant cell: CD68+

Election Microscopy

• Microvilli and mucin.

Treatment and Prognosis

• Extremely poor, 3% 3-year survival.

Cytogenetics

• High frequency of K-ras mutations

Reference

• AFIP

• Int J Pancreatol. 1997 Jun;21(3):243-8

• J Pancreas (Online) 2004; 5(6):512-515.

• Paal E, Thompson LD, Frommelt RA, Przygodzki RM, Heffess CS. A clinicopatholgic and Immunohistochemical Study of 35 Anaplastic carcinomas of the pancreas with a review of the literature. Ann Diagn Pathol 2001; 5:129-40.

• http://www.pathologyoutlines.com/pancreas.html

• AJSP 1998;22:1247

• Hum Path 2000;31:1223

• Archives 1998;122:266

• Archives 2002;126:1114