eMedicine Specialties > Oncology > Carcinomas of the Lung and Other Intrathoracic Carcinomas

Extrapulmonary Small Cell Carcinoma

Author: Irfan Maghfoor, MD, Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia
Contributor Information and Disclosures

Updated: Oct 14, 2008

Introduction

Background

Small cell carcinomas (SCC) commonly arise in the respiratory tract; however, it is not uncommon for these cells to arise in nonpulmonary sites, as extrapulmonary small cell carcinoma (EPSCC). Small cell carcinoma is a distinct clinical and pathologic entity that arises from cells of the amine precursor uptake and decarboxylation (APUD) system.

Extrapulmonary small cell carcinoma is estimated to account for approximately 1000 new cancer cases per year in the United States. This number, however, appears to be an underestimation. Most available literature on this condition exists in the form of case reports and retrospective series. The role of local and systemic therapies for extrapulmonary small cell carcinoma treatment is still not clearly defined. Most reports indicate chemotherapy sensitivity and response rates similar to those seen in small cell lung cancer with similar chemotherapeutic regimens. Surgery appears to play a more important role in the management of extrapulmonary small cell carcinoma compared to the role of surgery for small cell lung cancer.

Pathophysiology

Histologic criteria for diagnosis of extrapulmonary small cell carcinoma are same as those for pulmonary small cell carcinoma, that is appearance of uniform small cells with sparse cytoplasm, dense nuclei, and inconspicuous nucleoli.1 Since extrapulmonary small cell carcinoma has been reported from multiple sites, it is thought that the cell of origin is identical and derives from those originating in neural crest and then migrating to different epithelial sites within the body. These cells are characterized by presence of intracytoplasmic neurosecretory granules and stain positively with chromogranin.

Extrapulmonary small cell carcinoma has been reported to arise in almost all body sites except the central nervous system.2,3 Primary sites may include esophagus, salivary glands, gastrointestinal tract (including small intestine and large intestine), pancreas, larynx, cervix uteri, uterus, urinary bladder, prostate, breast, and lacrimal gland in addition to skin, where it is also referred to as Merkel cell carcinoma.4

Like pulmonary small cell carcinoma (lung cancer), small cell carcinomas arising from extrapulmonary sites may be associated with paraneoplastic syndromes, notably syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and hypercalcemia. However, deletions of chromosome arm 3p and c-myc amplification described in small cell pulmonary carcinoma have not been reported in extrapulmonary sites.

Frequency

United States

Approximately 1000 cases of extrapulmonary small cell carcinoma are reported annually, with an overall incidence of 0.1-0.4% of all cancers.

International

Global incidence of extrapulmonary small cell carcinoma is unknown.

Mortality/Morbidity

Because most of the literature is retrospective and in the form of case reports, estimating mortality rates is difficult. In addition, not all reported cases are managed uniformly, thereby making it further difficult to estimate prognosis. Long-term survival is, however, reported, especially in those treated with an aggressive multimodality approach.

Extrapulmonary small cell carcinoma may have a similar prognosis to that of small cell lung cancer. Those presenting with disseminated disease have a very poor prognosis and short survival time despite management with chemotherapy, radiation therapy, or both. Long-term survival is reported in those presenting with localized disease.

Age

No predilection for race or sex is clear in the reported literature. However, most of these malignancies develop after the sixth decade of life.

Clinical

History

Extrapulmonary small cell carcinoma is an aggressive neoplasm that enlarges rapidly and disseminates early in the course of illness. Due to multiplicity of sites where it can arise, there are no symptoms or signs specifically attributable to extrapulmonary small cell carcinoma. Patients may present with constitutional symptoms of fatigue, weakness, fever, weight loss, and night sweats. They may also have symptoms referable to the organ of origin, for instance hematuria in cases of bladder tumor, abdominal pain with or without obstruction with small or large bowel involvement, or hoarseness with laryngeal involvement.

Physical

Physical findings are again limited by the organ system involved and may include prostatic enlargement, skin nodules in case of Merkel cell carcinoma, or enlargement of regional draining lymph nodes.

As with pulmonary small cell carcinoma, paraneoplastic syndromes have been described with extrapulmonary small cell carcinoma. Most common of these are hypercalcemia, syndrome of inappropriate secretion of antidiuretic hormone, and secretion of adrenocorticotropic hormone, and patients may present with symptoms and signs of excess calcium, hyponatremia, or corticosteroid excess depending upon the severity and rate of development of endocrine abnormality.

Causes

Etiology of extrapulmonary small cell carcinoma is unknown. While some authors have reported an association with tobacco smoking, others have not found a strong causative correlation with tobacco.

More on Extrapulmonary Small Cell Carcinoma

Overview: Extrapulmonary Small Cell Carcinoma
Differential Diagnoses & Workup: Extrapulmonary Small Cell Carcinoma
Treatment & Medication: Extrapulmonary Small Cell Carcinoma
Follow-up: Extrapulmonary Small Cell Carcinoma
References
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References

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  2. Hueser CN, Nguyen NC, Osman M, Havlioglu N, Patel AJ. Extrapulmonary small cell sarcinoma: involvement of the brain without evidence of extracranial malignancy by serial PET/CT scans. World J Surg Oncol. Sep 25 2008;6:102. [Medline].

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  4. Pryor JG, Simon RA, Bourne PA, Spaulding BO, Scott GA, Xu H. Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas. Hum Pathol. Oct 3 2008;[Medline].

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  16. Pearse AG. Common cytochemical and ultrastructural characteristics of cells producing polypeptide hormones (the APUD series) and their relevance to thyroid and ultimobranchial C cells and calcitonin. Proc R Soc Lond B Biol Sci. May 14 1968;170(18):71-80. [Medline].

  17. Remick SC, Ruckdeschel JC. Extrapulmonary and pulmonary small-cell carcinoma: tumor biology, therapy, and outcome. Med Pediatr Oncol. 1992;20(2):89-99. [Medline].

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Further Reading

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Keywords

extrapulmonary small cell cancer, EPSCC, small cell cancer, lung cancer, lung cancer diagnosis, lung cancer treatment, lung carcinoma, respiratory tract cancer, respiratory tract cancer treatment, respiratory tract cancer diagnosis, respiratory tract carcinoma, small cell lung cancer, SCLC, paraneoplastic syndrome, syndrome of inappropriate secretion of antidiuretic hormone, SIADH, hypercalcemia, Merkel cell carcinoma

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Contributor Information and Disclosures

Author

Irfan Maghfoor, MD, Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia
Irfan Maghfoor, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Robert C Shepard, MD, FACP, Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International
Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting

 
 
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