Cytopathology Case 01

The smears are cellular with discohesive cells which are clearly recognized as malignant (fig. 1). Some cells are multinucleated giant cells but not of the osteoclastic type (fig. 2). The cells are large and pleomorphic with bizarre forms. There are occasional isolated, large, atypical columnar “tombstone cells” identified (fig. 3). The nuclei are hyperchromatic and are often eccentric with prominent nucleoli (fig. 4). The cytoplasm of other cells is stripped or transparent (fig. 5). There is an inflammatory infiltrate present with emperipolesis. Anisokaryotic daughter nuclei and cellular cannibalism can be seen. Some spindle-shaped cells are found, but there is no recognizable pigment present. The cytoplasm of many cells is dense and eosinophilic, with frequent mitoses (fig. 6). A background of necrosis, hemorrhage, and cystic degeneration is common.

DISCUSSION
Pancreatic ductal carcinomas comprise 90% of all pancreatic malignancies and are the 4th leading cause of cancer deaths in men and women. Variants of ductal carcinomas comprise 10–15% of these and include adenosquamous, anaplastic, osteoclastic giant cell, signet ring cell carcinoma, foamy gland adenocarcinoma, colloid (mucinous noncystic/gelatinous), clear-cell, and oncocytic carcinoma. Anaplastic and carcinosarcoma/sarcomatoid are all considered undifferentiated carcinomas.

Anaplastic carcinoma is also called pleomorphic giant cell carcinoma or sarcomatoid carcinoma depending on the dominant morphology.  Anaplastic carcinomas of the pancreas affect the same age (peak 60–80) and gender distribution (M>F 30%) as other pancreatic ductal carcinomas; however, they are more often located in the body or tail of the pancreas where symptoms are delayed until a later stage of disease. 

Pancreatic ductal cell carinomas in general carry a poor prognosis, with death occurring within 2 years. Prognosis is directly linked to resectability; however, only 5–10% are resectable at the time of diagnosis.  Anaplastic carcinoma of the pancreas carries the worst prognosis with a 5-year survival rate of only 3–4% which has not improved over the last decade. This malignancy is highly aggressive with a median survival of 2 months. Diagnosis is often made at late stages, and tumor size is often large (> 11 cm) with lymphatic and hematogenous metastasis.

Although ordinary ductal adenocarcinoma with evidence of intracytoplasmic mucin production are nearly always found within this entity, and some large cells may be seen in any ductal carcinoma, when they are a predominant feature, an anaplastic giant-cell variant must be considered. The differential diagnosis includes melanoma, lymphoma, sarcoma, and metastasis, especially metastatic giant-cell carcinoma of the lung, thyroid, adrenal, and liver, or malignant fibrous histiocytoma. Hepatocellular carcinoma may also be considered.

Although pancreatic duct carcinomas may be diagnosed by polymerase chain reaction (PCR) for mutations in the Ki-ras gene, along with an elevated carcinoembryonic antigen (CEA) by radioimmunoassay (RIA), there are no exclusively specific immunohistochemical or serologic markers for pancreatic carcinoma.  Besides ruling out a melanoma or lymphoma with S100 and CD45, an epithelial component may be identified with the use of keratin, EMA, or CEA immunohistochemical staining.  Staining, however, for AE1/AE3, CAM5.2, CA 19-9, and CEA vary from 38–63% so may be of limited value.  Staining patterns are also often variegated or focal.

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References

1. Koss L, Melamed M. 2006. Koss’ diagnostic cytopathology and its histopathologic bases. Philadelphia: Lippencott Williams & Wilkins, 1439–46.

2. Chhieng D, Stelow E. 2007. Pancreatic cytopathology. New York: Springer Science+Business Media, Inc., 35–74.

3. Orell S, et al. 2005. Fine needle aspiration cytology. Philadelphia: Elsevier Limited, 299–308.

4. Layfield L, Bentz J. Giant-cell containing neoplasms of the pancreas: an aspiration cytology study. Diagnostic Cytopathology 2007;36(4):238–44.