The Pathology of Extrapulmonary Small Cell Carcinoma
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
References (203)
- et al.
Small cell carcinoma of the cervix: A clinicopathologic and immunohistochemical study of 23 cases
Ann Diagn Pathol
(2002) - et al.
Primary undifferentiated small cell carcinoma of the esophagus
Hum Pathol
(1999) - et al.
Primary mammary small-cell carcinoma: A molecular analysis of 2 cases
Hum Pathol
(2001) - et al.
Primary small cell carcinoma of the pancreas
Pathology
(1993) - et al.
Small cell carcinoma of the tonsil
Otolaryngol Head Neck Surg
(1995) - et al.
Small cell carcinoma of the oral cavity: Report of a case
J Oral Maxillofac Surg
(2001) - et al.
Primary combined small cell carcinoma of the larynx
Am J Otolaryngol
(1985) - et al.
Small cell carcinoma of the larynx and ectopic antidiuretic hormone secretion
Otolaryngol Head Neck Surg
(1995) - et al.
Molecular abnormalities associated with endocrine tumors of the uterine cervix
Gynecol Oncol
(1999) - et al.
Nonsquamous cancer of the vagina
Gynecol Oncol
(1988)
Vaginal small cell carcinoma mimicking a Bartholin’s gland abscess: A case report
Gynecol Oncol
Small cell carcinoma with neurosecretory granules arising in an ovarian dermoid cyst
Gynecol Oncol
Chromosome abnormalities and p53 expression in a small cell carcinoma of the bladder
Cancer Genet Cytogenet
Primary small cell carcinoma of the bladder: A report of 25 cases
J Urol
c-kit Expression in small cell carcinoma of the urinary bladder: Prognostic and therapeutic implications
Mod Pathol
Small cell carcinoma of the bladder and prostate
Urology
Small-cell carcinoma of the seminal vesicle responding to chemotherapy
Ann Oncol
Extrapulmonary small cell carcinoma
South Med J
Extrapulmonary and pulmonary small-cell carcinoma: Tumor biology, therapy, and outcome
Med Pediatr Oncol
Undifferentiated small cell carcinomas in extrapulmonary sites
Semin Oncol
Oat-cell tumors of mediastinal glands
J Pathol Bacteriol
Small cell carcinoma of the lung: Cellular origin and relationship to other neoplasms
Semin Oncol
The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept
J Histochem Cytochem
Thymic carcinomas: Histopathological varieties and immunohistochemical study
Am J Surg Pathol
Small cell carcinoma of the uterine cervix: Pathologic analysis of 9 cases
TaiwanYi Xue Hui Za Zhi
Small-cell carcinoma of the endometriumA clinicopathological study of sixteen cases
Am J Surg Pathol
Primary ovarian small cell carcinoma of pulmonary typeA clinicopathologic, immunohistologic, and flow cytometric analysis of 11 cases
Am J Surg Pathol
A case of small cell carcinoma of the stomach
Hepatogastroenterology
Tripartite differentiation in a carcinoma of the duodenum
Cancer
Small-cell undifferentiated carcinoma of the colonA clinicopathological study of five cases and their association with colonic adenomas
Am J Surg Pathol
Primary mixed adenocarcinoma and small cell carcinoma of the appendix: A clinicopathologic, immunohistochemical, and molecular study of a hitherto unreported tumor
Am J Surg Pathol
Small-cell carcinoma combined with adenocarcinoma of the gallbladderA case report with immunohistochemical and flow cytometric studies
Arch Pathol Lab Med
Small-cell carcinoma of the ampulla of Vater and a paraneoplastic syndrome
N Z Med J
Composite neuroendocrine and adenocarcinoma of the common bile duct associated with Clonorchis sinensis: A case report
Hepatogastroenterology
Small cell carcinoma of the pancreas and biliary tract
J Surg Oncol
Combined small-cell and transitional cell carcinoma of the renal pelvisA light microscopic, immunohistochemical, and ultrastructural study of a case with literature review
Arch Pathol Lab Med
Mixed adenocarcinoma and neuroendocrine carcinoma arising in the urachusA case report and review of the literature
Eur Urol
Small cell carcinoma of the bladder: A contemporary clinicopathological study of 51 cases
Histopathology
Neuroendocrine differentiation in prostatic carcinomasA retrospective autopsy study
Arch Pathol Lab Med
Small cell carcinoma of the breast: A clinicopathologic and immunohistochemical study of nine patients
Am J Surg Pathol
Differentiation of a cell line of human cervical argyrophil small cell carcinoma to macrophage lineage cells
Jpn J Cancer Res
Small-cell carcinomas of the gastrointestinal tract: A review
J Clin Oncol
Progression of prostate cancer to neuroendocrine cell tumor
Int J Urol
An unusual composite endometrial tumor combining papillary serous carcinoma and small cell carcinoma
Am J Surg Pathol
Prostate cancer with a normal PSA: small cell carcinoma of the prostate--a rare entity
J Am Board Fam Pract
Progression from adenocarcinoma to small cell carcinoma of the prostate with normalization of prostate-specific antigen (PSA) levels
Scand J Urol Nephrol
Chromosomal imbalances in small cell carcinomas of the urinary bladder
J Pathol
Small cell carcinoma of the esophagus in a patient with longstanding primary achalasia
Am J Gastroenterol
Small cell carcinoma of the esophagus in a cirrhotic patient
Endoscopy
Small cell carcinoma of the esophagus
Cancer
Cited by (83)
Incorporation of immunotherapy into the treatment of metastatic neuroendocrine carcinoma of the cervix: A case report
2023, Gynecologic Oncology ReportsIpilimumab and nivolumab for recurrent neuroendocrine cervical carcinoma
2022, Gynecologic Oncology ReportsThe puzzle of gynecologic neuroendocrine carcinomas: State of the art and future directions
2021, Critical Reviews in Oncology/HematologyNeuroendocrine carcinoma of the endometrium: Disease course, treatment, and outcomes
2019, Gynecologic OncologyA Human Adult Stem Cell Signature Marks Aggressive Variants across Epithelial Cancers
2018, Cell ReportsCitation Excerpt :Squamous cell carcinomas from different anatomical sites share frequent alterations in TP53, PIK3CA, CDKN2A, SOX2, and CCND1 compared with other cancer phenotypes (Schwaederle et al., 2015). Almost every epithelial tissue can develop a highly aggressive cancer phenotype characterized in part by expression of neuroendocrine differentiation markers (Frazier et al., 2007). These neuroendocrine cancers encompass a spectrum of different histological phenotypes, including small cell, large cell, adenocarcinoma with neuroendocrine differentiation, and others.
Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Clinical and Imaging Review
2018, Current Problems in Diagnostic RadiologyCitation Excerpt :Several hormonal markers are elevated with SCCOPT including serotonin, insulin, somatostatin, gastrin, and calcitonin.14 SCCOPT is also associated with paraneoplastic syndromes such as Cushing syndrome, syndrome of inappropriate antidiuretic hormone secretion, cerebellar cortical degeneration, and paraneoplastic retinopathy.14 SCCOHT is a highly undifferentiated tumor with uncertain histogenesis; it is postulated to be epithelial, germinal, or mesenchymal in origin.