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CARCINOMA PLEURAL A CELULAS PEQUEÑAS: ACTUALIZACIÓN

(especial para SIIC © Derechos reservados)

En este artículo se hace una revisión sobre informes de casos de carcinoma de células pequeñas extrapulmonar, una enfermedad inusual. Se discuten diagnósticos diferenciales y su relación con el asbesto.
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Autor:
H. F. M van der Heijden
Columnista Experto de SIIC

Artículos publicados por H. F. M van der Heijden
Coautores
Yvonne F Heijdra (MD, PhD)*  Hans Bulten (MD, PhD)**  Jan Festen (MD PhD)*** 
University Medical Centre St Radboud, Department of Pulmonary Diseases, Nijmegen, Países Bajos*
University Medical Centre St Radboud, Department of Pathology, Nijmegen, Países Bajos**
University Medical Centre St Radboud, Department of Pulmonary Disease, Nijmegen, Países Bajos***
Recepción del artículo
21 de octubre, 2003 		Primera edición
4 de febrero, 2004 		Segunda edición, ampliada y corregida
7 de junio, 2021
Resumen
El carcinoma a células pequeñas extrapulmonar (CCP) es una enfermedad muy rara y la manifestación primaria pleural es extremadamente inusual. Este artículo hace una revisión de la literatura disponible, que consiste en informes de casos, incluyendo nuestro propio caso de CCP pleural en un paciente con placas pleurales preexistentes relacionadas con el asbesto (1). Se discuten los diagnósticos diferenciales de masas pleurales que necesitan ser diferenciadas del CCP pleural y la relación del CCP pleural con la exposición al asbesto.

Palabras clave
Enfermedad pleural, carcinoma de células pequeñas, quimioterapia, asbesto

Abstract
Extrapulmonary small cell carcinoma (SCC) is a very rare disease and a primary pleural manifestation is extremely rare. This paper reviews the available literature which consists of case reports including our own case of SCC of the pleura in a patient with pre-existent asbestos-related pleural plaques (1). Differential diagnosis of pleural masses that need to be differentiated from pleural SCC is discussed and the relation of pleural SCC with asbestos exposure is discussed.

Key words
Pleural disease, small cell carcinoma, chemotherapy, asbestos.

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Principal: Oncología
  Relacionadas: Anatomía Patológica, Neumonología

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Especialidad principal:
Oncología


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Artículo completo

PLEURAL SMALL CELL CARCINOMA: AN UPDATE

IntroductionAn extensive literature search (PubMed and current contents) revealed four case presentations of a primary presentation of pleural SCC (1-4). Extrapulmonary small cell carcinomas (SCC) are uncommon (5;6), and primary localization of a SCC in the pleura is very rare. Levenson et.al. (5) described 8 patients (4%) with exclusive extrapulmonary localization of SCC in a series of 203 patients with pulmonary SCC (5). The primary site of SCC in these cases and the literature survey (n=70) reported in this paper showed that the most frequently reported site of extrapulmonary SCC was the esophagus (22%), salivary glands (20%), larynx (17%) skin and cervix (both 13%) and stomach (6%) (5). Skin SCC is also described as Merkel cell tumor (7). Pazdur and colleagues described 6 cases of primary extrapulmonary localization, none of them with a primary pleural localization (6).In the four reported cases of pleural SCC two had a history of asbestos exposure (1;2). Our patient was the only case of primary pleural SCC and pre-existent asbestos-related pleural plaques (1). In the case of pleural SCC presented by Bouvier and Bell asbestos exposure was reported but asbestos-related pleural disease or pulmonary disease on chest X-ray or CT-scan was not described (2). A third case of pleural SCC was found in a patient with prior ipsilateral tuberculosis, lobectomy for bronchiectasis and post-surgery empyema (4). In the last reported case of pleural SCC no previous pleural abnormalities were reported (3). All reported patients were heavy smokers with a tobacco exposure range of 30 to70 pack years. A summary of the case reports of patients with pleural SCC we have found in our literature search is given in Table 1.Table 1.Diagnosis and differential diagnosisTo adequately diagnose this rare disease it is of great importance to supply the pathologist with a sufficient amount of tissue to allow the required immunohistochemical investigations. The differential diagnosis of pleural masses includes malignant mesothelioma, benign fibrous mesothelioma, pleural localization of malignant lymphoma and metastatic pleural disease. The most important differential diagnosis of pleural mass without parenchymal lung abnormalities (especially in a patients with known asbestos exposure or evidence of asbestos exposure) is malignant mesothelioma. This differentiation can be difficult since it is known that some features of SCC may be observed in typical malignant mesothelioma (8;9). Also a similar pattern of deletions on chromosome 4 have been reported in both malignant mesothelioma and small cell lung carcinoma suggesting a similar pathogenesis (10). Another rare malignant tumor that is part of the differential diagnosis for pleural SCC is a pleural localization of a desmoplastic small round cell tumor (11;12). Desmoplastic small round cell tumors are characterized by nests of small tumor cells surrounded by a cellular and vascular collagenous stroma, hence the name desmoplastic small round cell tumor. The amount of stroma varies with the progression of the tumor, although the stroma is always seen. WT1, a polyclonal antibody against the amino terminus of the WT1 protein, has shown positive staining in more than 95% of cases and can be used to differentiate this tumor from SCC (11;12). In our patient (1) no evidence was found of typical histological features of mesothelioma or desmoplastic small round cell tumor. The immunohistochemical evaluation showed clear positive staining for keratin and neurorendocrine markers (Cam 5.2, keratin and chromogranine, synaptophysine, CD56, respectively) and negative staining for lymphocyte marker LCA (1). These features support the diagnosis of SCC.Relation with asbestos exposureAsbestos exposure is related to an increased risk of development of asbestosis (interstitial pulmonary fibrosis) and pleural diseases such as pleural plaques, pleural thickening and malignant mesothelioma. The pathogenesis and molecular basis of these diseases were reviewed recently (13) and the presence of asbestosis is associated with an increased risk of lung cancer (14). The incidence of the various histological types of the lung cancers do not seem to be affected by the exposure to asbestos (15;16). Pulmonary malignancies of all histological types including small cell lung carcinoma (SCLC) are found in patients with asbestos exposure (15;17). In a recent review of 500 cases of malignant mesothelioma synchronous malignancies were detected in 9 patients (1.8%) (18). From these 9 patients 6 had a pulmonary carcinoma (3 adenocarcinomas, 2 squamous cell carcinomas and one SCC) (18). Asbestos-induced pleural fibrosis is the most common radiographic finding among those exposed to asbestos (19). The two major known risk factors for bronchogenic carcinoma are smoking and asbestos exposure and these risk factors have a synergistic effect so that individuals who are exposed to asbestos and cigarette smoke have an approximate 30 to 50-fold increased risk of developing lung cancer (16). To our knowledge no new data has been published after publication of our case report describing other cases of a SCC of the pleura in a patients with asbestos related pleural disease. AbbreviationsCEA: carcino embyonic antigenSCC: small cell carcinomaSCLC: small cell lung carcinomaSIADH: syndrome of inappropriate ADH secretion
Bibliografía del artículo
  1. Van der Heijden HFM, Heijdra YF, Bulten J, Festen J. Pleural small cell carcinoma in pre-existent asbestos related pleural disease. Lung Cancer 2002; 35(1):91-94.
  2. Bouvier DP, Bell B. Small cell carcinoma of the pleura. South Med J 1989; 82(11):1437-1438.
  3. Satoh H, Ishikaua H, Ohtsuka M, Sekizawa K. Small cell carcinoma of the pleura. South Med J 2002; 95(10):1221.
  4. Schinkewitch P, Gasser B, Wihlm JM, Pauli G, Quoix E. Small cell carcinoma of the pleura. A case report. Lung Cancer 1996; 16(1):87-94.
  5. Levenson RM, Jr., Ihde DC, Matthews MJ, Cohen MH, Gazdar AF, Bunn PA, Jr. et al. Small cell carcinoma presenting as an extrapulmonary neoplasm: sites of origin and response to chemotherapy. J Natl Cancer Inst 1981; 67(3):607-612.
  6. Pazdur R, Bonomi P, Gould VE, Yordan E, Roseman D, Holinger L et al. Neuroendocrine small cell carcinomas in miscellaneous primary sites: implications for staging and therapy. Anticancer Res 1981; 1(6):335-340.
  7. Goessling W, McKee PH, Mayer RJ. Merkel cell carcinoma. J Clin Oncol 2002; 20(2):588-598.
  8. Mayall FG, Gibbs AR. The histology and immunohistochemistry of small cell mesothelioma. Histopathology 1992; 20(1):47-51.
  9. Cook HC. Small cell mesothelioma. Histopathology 1993; 22(3):294-295.
  10. Shivapurkar N, Virmani AK, Wistuba II, Milchgrub S, Mackay B, Minna JD et al. Deletions of chromosome 4 at multiple sites are frequent in malignant mesothelioma and small cell lung carcinoma. Clinical Cancer Research 1999; 5(1):17-23.
  11. Ostoros G, Orosz Z, Kovacs G, Soltesz I. Desmoplastic small round cell tumour of the pleura: a case report with unusual follow-up. Lung Cancer 2002; 36(3):333-336.
  12. Syed S, Haque AK, Hawkins HK, Sorensen PH, Cowan DF. Desmoplastic small round cell tumor of the lung. Arch Pathol Lab Med 2002; 126(10):1226-1228.
  13. Kamp DW, Weitzman SA. The molecular basis of asbestos induced lung injury. Thorax 1999; 54(7):638-652.
  14. Weiss W. Asbestosis: a marker for the increased risk of lung cancer among workers exposed to asbestos. Chest 1999; 115(2):536-549.
  15. de Klerk NH, Musk AW, Eccles JL, Hansen J, Hobbs MS. Exposure to crocidolite and the incidence of different histological types of lung cancer. Occup Environ Med 1996; 53(3):157-159.
  16. Lee BW, Wain JC, Kelsey KT, Wiencke JK, Christiani DC. Association of cigarette smoking and asbestos exposure with location and histology of lung cancer. Am J Respir Crit Care Med 1998; 157(3 Pt 1):748-755.
  17. Levin JL, O'Sullivan MF, Corn CJ, Williams MG, Dodson RF. Asbestosis and small cell lung cancer in a clutch refabricator. Occup Environ Med 1999; 56(9):602-605.
  18. Attanoos RL, Thomas DH, Gibbs AR. Synchronous diffuse malignant mesothelioma and carcinomas in asbestos-exposed individuals. Histopathology 2003; 43(4):387-392.
  19. Hillerdal G. Nonmalignant pleural disease related to asbestos exposure. Clin Chest Med 1985; 6(1):141-152.

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