Elsevier

Seminars in Oncology

Volume 34, Issue 1, February 2007, Pages 30-38
Seminars in Oncology

The Pathology of Extrapulmonary Small Cell Carcinoma

https://doi.org/10.1053/j.seminoncol.2006.11.017Get rights and content

Extrapulmonary small cell carcinomas (EPSCCs) are uncommon malignant neoplasms with a reported incidence of 0.1% to 0.4% in the United States. Since their first description in 1930, they have been seen in nearly every organ system. Like their more common pulmonary counterparts, EPSCCs are thought to arise from a multipotential stem cell. However, there is recent molecular evidence that small cell elements may arise as a late-stage phenomenon in the genetic progression of more organ-typical carcinomas. The morphologic, immunohistochemical, and ultrastructural features are similar to those described in pulmonary small cell carcinomas (PSCCs). The differential diagnosis of EPSCC includes PSCC, other neuroendocrine tumors, small round blue cell tumors, metastatic melanoma, lymphoma, and poorly differentiated non-small cell carcinomas. Molecular alterations reported to occur in EPSCCs include abnormalities described in PSCC and changes found in carcinomas more typically encountered in the organ from which they arise. In this article we discuss the pathology of EPSCC with a review of theories of histogenesis, sites of occurrence, diagnostic features, differential diagnosis, molecular alterations, and clinical behavior.

Section snippets

Histogenesis

Just as pulmonary small cell carcinomas (PSCCs) were once presumed to have their origin in the Kultchisky cell,5 EPSCCs were speculated to arise from the amine-precursor uptake and decarboxylase (APUD) cells described by Pearse in 1969.6 These cells were said to comprise a diffuse neuroendocrine system, and to have ultrastructural features shared by many small cell carcinomas. As such, the APUD system provided an attractive putative cell of origin for EPSCC.3 However, this theory offers little

Sites of Occurrence

EPSCC has been reported in nearly every organ in either pure or mixed form. In the digestive and hepatobiliary tracts, it has been documented in the esophagus,12, 34, 35, 36, 37, 38, 39, 40, 41 stomach,42, 43 duodenum,14, 44 appendix,16 colon,15 rectum,45, 46 anus,47 ampulla of vater,48 gallbladder,17, 49, 50 pancreas,20, 51, 52 common bile duct,19, 53 and liver.54 In the head and neck, it has been reported in the tonsil,55, 56 the nasal cavity and paranasal sinuses,57 oral cavity,58, 59 minor60

Diagnosis

The morphology of EPSCC is identical to its pulmonary counterpart. The architecture is generally solid; however, irregular organioid groupings, trabeculae, and rosette-like patterns may be present. The cells are generally two to three times the diameter of a mature lymphocyte with finely dispersed chromatin, inconspicuous nucleoli, and scant cytoplasm. Nuclei frequently conform around the nuclei of adjacent cells (nuclear molding). Mitotic activity and necrosis are generally prominent. The

Differential Diagnosis

The differential diagnosis of EPSCC is large. It includes metastatic PSCC, other neuroendocrine tumors, various small round blue cell tumors, metastatic melanoma, lymphoma, and poorly differentiated carcinoma.

Metastatic PSCC, which displays morphology identical to that of EPSCC, must be excluded by a normal plain radiograph and computed tomography scan of the chest and a normal sputum cytology or negative bronchoscopy.123 Initially TTF-1 immunostaining, found in 90% of PSCCs, was thought to be

Molecular Alterations

Most information on molecular alterations of EPSCC is derived from isolated case reports and small series. Although information is limited, EPSCCs generally appear to share some molecular abnormalities both with PSCC and with carcinomas more typically encountered in the organ involved.

One of the most consistent chromosomal abnormalities seen in PSCC is loss of genetic material from the short arm of chromosome 3.135 Although one report of five cases published in 1989 found no such abnormalities

Clinical Behavior

EPSCC is an uncommon entity, with an incidence of 0.1% to 0.4% or approximately 1,000 new cases diagnosed each year in the United States. By definition, patients must have a histologic diagnosis of small cell carcinoma, a normal plain radiograph and computed tomography scan of the chest, and a normal sputum cytology or negative bronchoscopy.123

EPSCCs mainly affects patients middle-age or older, with more than 70% of patients being older than 50 years. EPSCC of the uterine cervix is an

Summary

EPSCCs are uncommon malignancies that are thought to arise either from a multipotential stem cell, or as a late-stage phenomenon in the genetic progression of a more organ typical carcinoma. They are aggressive neoplasms, which are often disseminated at presentation. Morphologically, immunohistochemically, and ultrastructurally, they are indistinguishable from their more common pulmonary counterparts. They share some molecular features with both PSCCs and carcinomas more commonly seen in the

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