Small-cell carcinoma

Small-cell carcinoma
Small cell carcinoma
Classification and external resources

Micrograph of a small cell carcinoma of the lung showing cells with nuclear moulding, minimal amount of cytoplasm and stippled chromatin. FNA specimen. Field stain.
ICD-O: M8041/3
MedlinePlus 000122
eMedicine med/1336
MeSH D018288

Small cell carcinoma (sometimes rendered as "small-cell carcinoma" or "Oat-cell carcinoma") is a type of highly malignant cancer that most commonly arises within the lung,[1] although it can occasionally arise in other body sites, such as the cervix[2] and prostate.[3]

Pie chart showing incidence of small cell lung cancer (shown in red at right), as compared to other lung cancer types, with fractions of smokers versus smokers shown for each type.[4]

Contents

Histopathology

Small cell carcinoma is an undifferentiated neoplasm composed of primitive-appearing cells.

Paraneoplastic Syndromes

In a not-insignificant number of cases, small cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone (ACTH) and anti-diuretic hormone (ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate production of anti-diuretic hormone (SIADH).

Lambert-Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small cell carcinoma.[5]

Lung

Histopathologic image of small cell carcinoma of the lung. CT-guided core needle biopsy. H&E stain.

When associated with the lung, it is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm.

It is thought to originate from neuroendocrine cells (APUD cells) in the bronchus called Feyrter cells (named for Friedrich Feyrter).[6] Hence, they express a variety of neuroendocrine markers, and may lead to ectopic production of hormones like ADH and ACTH that may result in paraneoplastic syndromes and Cushing's syndrome.[7] Approximately half of all individuals diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) will eventually be found to have a small cell carcinoma of the lung.[5]

Small cell carcinoma is most often more rapidly and widely metastatic than non-small cell lung carcinoma[8] (and hence staged differently). There is usually early involvement of the hilar and mediastinal lymph nodes. [7]

Combined small cell lung carcinoma (c-SCLC)

Small cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancer,[9] including extremely complex malignant tissue admixtures.[10] .[11] When it is found with one or more differentiated forms of lung cancer, such as squamous cell carcinoma or adenocarcinoma, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma (c-SCLC).[9] C-SCLC is the only currently recognized subtype of SCLC.[9]

Although combined small cell lung carcinoma is currently staged and treated similarly to "pure" small cell carcinoma of the lung, recent research suggests surgery might improve outcomes in very early stages of this tumor type.

Smoking is a significant etiological factor.

Symptoms and signs are as for other lung cancers. In addition, because of their neuroendocrine cell origin, small cell carcinomas will often secrete substances that result in paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome.

Small cell carcinoma of the prostate

In the prostate, small cell carcinoma (SCCP) is a rare form of cancer (approx 1% of PC).[12] Due to the fact that there is little variation in prostate specific antigen levels, this form of cancer is normally diagnosed at an advanced stage, after metastasis.

It can metastasize to the brain.[13]

Treatment for small cell lung carcinoma

Small cell lung carcinoma has long been divided into two clinicopathological stages, including limited stage (LS) and extensive stage (ES). The stage is generally determined by the presence or absence of metastases, whether or not the tumor appears limited to the thorax, and whether or not the entire tumor burden within the chest can feasibly be encompassed within a single radiotherapy portal.[14]

In cases of LS-SCLC, combination chemotherapy (often including cyclophosphamide, cisplatinum, doxorubicin, etoposide, vincristine and/or paclitaxel) is administered together with concurrent chest radiotherapy (RT).

Chest RT has been shown to improve survival in LS-SCLC.

Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. Unfortunately, relapse is the rule, and median survival is only 18 to 24 months.

Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to CT and/or RT, there has been little role for surgery in this disease since the 1970s.[15] However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy.("adjuvant chemotherapy").[16]

In ES-SCLC, combination chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms such as dyspnea, pain from liver or bone metastases, or for treatment of brain metastases, which, in small cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.

Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, however.

If complete response to chemotherapy occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.

All in all, small cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low.

Prognosis

In limited stage disease, median survival with treatment is 14–20 months, and about 20% of patients with limited stage small cell lung carcinoma live 5 years or longer.

The prognosis is far worse in extensive stage small cell lung carcinoma, with treatment, median survival is just 8–13 months, and only 1-5% of patients with extensive stage small cell lung carcinoma treated with chemotherapy live 5 years or longer.

See also

References

  1. ^ "small-cell carcinoma" at Dorland's Medical Dictionary
  2. ^ Nasu K, Hirakawa T, Okamoto M, Nishida M, Kiyoshima C, Matsumoto H, Takai N, Narahara H. Advanced small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy with irinotecan and cisplatin followed by radical surgery. Rare Tumors 2011;3(1):e6.
  3. ^ Capizzello A, Peponi E, Simou N, Ntaskagiannis D, Tasiou I, Kamina S, Tsekeris P. Pure small cell carcinoma of the prostate: a case report and literature review. Case Rep Oncol 2011;4:88-95.
  4. ^ Smokers defined as current or former smoker of more than 1 year of duration. See image page in Commons for percentages in numbers. Reference:
  5. ^ a b Titulaer MJ, Verschuuren JJ. Lambert-Eaton myasthenic syndrome: tumor versus nontumor forms. Ann N Y Acad Sci 2008;1132:129–134.
  6. ^ Champaneria MC, Modlin IM, Kidd M, Eick GN (2006). "Friedrich Feyrter: a precise intellect in a diffuse system". Neuroendocrinology 83 (5-6): 394–404. doi:10.1159/000096050. PMID 17028417. http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000096050. 
  7. ^ a b Chapter 13, box on morphology of small cell lung carcinoma in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7.  8th edition.
  8. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 759. ISBN 0-7216-0187-1. 
  9. ^ a b c Travis, William D; Brambilla, Elisabeth; Muller-Hermelink, H Konrad et al., eds (2004). Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. World Health Organization Classification of Tumours. Lyon: IARC Press. ISBN 92 832 2418 3. http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-cover.pdf. Retrieved 27 March 2010. 
  10. ^ Pelosi G, Sonzogni A, Galetta D, Perrone F, Braidotti P, Manzotti M, Fabbri A, Spaggiari L, Veronesi G, Viale G. Combined small-cell carcinoma of the lung with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type. Virchows Arch 2011;458:497-503.
  11. ^ Gotoh, Masashi; Yamamoto, Yasumichi; Huang, Cheng-Long; Yokomise, Hiroyasu (2004). "A combined small cell carcinoma of the lung containing three components: small cell, spindle cell and squamous cell carcinoma". European Journal of Cardio-Thoracic Surgery (Elsevier) (26): 1047–9. http://ejcts.ctsnetjournals.org/cgi/content/abstract/26/5/1047. Retrieved 27 March 2010. 
  12. ^ Nutting C, Horwich A, Fisher C, Parsons C, Dearnaley DP (June 1997). "Small cell carcinoma of the prostate". Journal of the Royal Society of Medicine 90 (6): 340–1. PMC 1296316. PMID 9227387. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1296316. 
  13. ^ Erasmus CE, Verhagen WI, Wauters CA, van Lindert EJ (November 2002). "Brain metastasis from prostate small cell carcinoma: not to be neglected". Can J Neurol Sci 29 (4): 375–7. PMID 12463494. http://cjns.metapress.com/openurl.asp?genre=article&issn=0317-1671&volume=29&issue=4&spage=375. 
  14. ^ Argiris A, Murren JR. Staging and clinical prognostic factors for small-cell lung cancer. Cancer J 2001;7:437-47.
  15. ^ Mountain C. Clinical biology of small cell carcinoma: relationship to surgical therapy. Semin Oncol 1978;5:272–279.
  16. ^ Shepherd, F. Surgery for limited stage small cell lung cancer: Time to fish or cut bait

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