Small Cell Carcinoma Tumors - Research Paper Example

Small Cell Carcinoma Clinical features and Histopathology Small cell carcinoma is a malignant epithelial tumor comprisedof small cells with defined cytoplasmic border, absent or inconspicuous nucleoli, scant cytoplasm, and finely granular “salt and pepper” pattern of the nuclear chromatin. Its malignant neuroendocrine neoplasm produced from the urothelium, tends to behave like its pulmonary counterpart (Devilee & Tavassoli 135). Most commonly, the cells affected by small cell carcinomas are 2-3 times of the lymphocyte size, but if better preserved, can be larger with more visible nucleoli and more open chromatin form (Gray 65). In bronchoscopic brush specimen, the tumor cells possessed more tissue fragments than in the sputum. In fine needle aspiration (FNA) specimens, both transthoracic and transbronchial, varying quantities of tissue fragments and single cells linked with apoptotic bodies and necrotic debris were observed. The loss of chromatin pattern can be induced by the degenerative changes, making the nuclei pale-staining with haematoxylin. Moreover, almost 50% of the reported cases of small cell carcinoma have areas affected by urothelial carcinoma, particularly andenocarcinoma and squamous cell carcinoma (Devilee & Tavassoli 135). The existence of these differentiated areas concurs with the diagnosis of small cell carcinoma. Most patients with small cell carcinoma of the bladder experience haematuria. Other patients reported localized abdominal/pelvic pain or dysuria. About 56% of patients, at the time of diagnosis, had metastatic disease commonly located at the lungs, regional lymph nodes, liver, and bones (Devilee & Tavassoli 135). Peripheral neuropathy, induced by the paraneoplastic syndrome, can also be an indication of metastatic disease. The paraneoplastic syndrome is likely caused by the tumor production of antineuronal autoantibodies. It was also reported that electrolyte level abnormalities like hypophosphatemia, ectopic secretion of adrenocorticotropic hormone, and hypercalcemia are symptoms of the paraneoplastic syndrome that are associated with the small cell carcinoma of the bladder. Meanwhile, most of the small cell carcinomas of the urinary tract originated from the urinary bladder (Devilee & Tavassoli 135). The tumors look like a large solid, polypoid, nodular, isolated mass with or without ulceration that can widely infiltrate the wall of the bladder. The most common topographies are the dome and the vesical lateral walls. The tumors are invasive, consisting of small cells with nuclei containing finely stippled chromatin, inconspicuous nucleoli, scant cytoplasm, and nuclear molding (Devilee & Tavassoli 135). Necrosis along with DNA encrustation of blood vessels walls is typically observed. Prognosis, Diagnosis, and Treatment The tumors caused by small cell carcinoma are characterized by a rapid clinical course with early muscular and vascular invasion. For patients with small carcinoma of the bladder, the reported overall five-year survival rate was as low as 8% (Devilee & Tavassoli 136). The overall prognosis has been linked with the stage of the disease at presentation. The clinical stage, however, was suggested as dependently associated with survival. This suggestion was based on the notion that micrometastasses are already present when a patient was diagnosed with clinically localized disease. Patients of ages higher than 65 years, at high TNM stage, with metastatic disease at presentation have a poor survival rate (Devilee & Tavassoli 136). As well, the clinical treatments, involving radiotherapy, cystectomy, or chemotherapy, have variable success. The small cell carcinoma tumors are diagnosed by a number of methods, including, electron microscopy, immunohistochemical method, and histochemical method (Devilee & Tavassoli 135). Further, the diagnosis of small cell carcinoma can be performed on morphologic basis alone, even though the neuroendocrine differentiation can hardly be demonstrated. Findings from comparative genomic hybridization research suggest that the small cell carcinoma of the urinary bladder is a genetically unstable tumor, showing different cytogenetic changes. The tumors exhibit heterogeneous and complex cytogenetic changes, including alterations in chromosomes, 6, 9, 11, 13, and 18 (Devilee & Tavassoli 135). Synaptophysin and chromogranin A are the common neuroendocrine markers demonstrable in the cytoplasm of the small cell carcinomas, whereas the antibodies to CD56 were proven as the most reliable confirmation of small cell carcinoma (Gray 64). The tumor is frequently hilar or central in position, which disseminates widely, grows aggressively, and has a very poor overall prognosis. At stage I, tumors are rarely histologically or cytologically detected (Gray 64). In general, small cell carcinoma possesses a few intracytoplasmic dense core neurosecretory granules amassed by small cytoplasmic processes. If neuroendocrine granules are not detected in a tumor through electron microscopy and there is diagnostic difficulty, but there are some ultrastructural evidences of squamous or glandular differentiation, this scenario would shroud some doubt on the diagnosis of small cell carcinoma. Some aggressively behaving small cell tumors may ultrastructurally exhibit variable combinations of neuroendocrine or squamous glandular differentiation. Tumors due to small cell carcinoma commonly appear in sputum in small rounded or elongated aggregates within streaks of mucus (Gray 65). The aggregates usually occur with a complement of dissociated cells. The tumor cells, in small to medium sizes and with minimal cytoplasm, show nuclear pleomorphism within the aggregates, along with nuclear outline irregularity and nuclear molding. A uniformly hyperchromatic nucleus with a stippled or flat chromatin form is typically observed, but the nucleoli are inconspicuous. Within the aggregates, apoptotic cell breakdown and necrosis indicate a high mitotic rate and cell turnover. The tumor cells’ close apposition in an aggressively growing tumor with fragile nuclei and minimal cytoplasm creates helpful characteristic of nuclear molding, which is rarely seen in lung carcinomas (Gray 66). This characteristic may result in formation small concentrically arranged groups or single file arrangements. In addition, in some small cell carcinoma cases, a tumor cell’s engulfment of a single, apoptotic nuclear fragment was observed (Gray 66). Summary Small cell carcinoma is a malignant epithelial tumor comprised of small cells with defined cytoplasmic border, absent or inconspicuous nucleoli, scant cytoplasm, and finely granular “salt and pepper” pattern of the nuclear chromatin. It is primarily characterized by conspicuous nuclear molding, extensive necrosis, and high mitosis rate. Tumor cells in sputum specimens appear as single cells, linear forms, and small groups in mucus strands, and are typically associated with a necrotic background. In bronchoscopic brush specimen, the tumor cells possessed more tissue fragments than that of the sputum. In FNA specimens, both transthoracic and transbronchial, varying quantities of tissue fragments and single cells linked with apoptotic bodies and necrotic debris were observed. Most tumor cells are slightly bigger than small lymphocytes or approximately three times the size of a mature lymphocyte with ill-defined, scant cytoplasm. The nuclei of tumor cells are either spindle, round, or oval in shape. Well-preserved tumor cells possessed well-dispersed granular chromatin formation, whereas the less preserved ones commonly have diffuse hyperchromatin. The small cell carcinoma tumors are diagnosed by a number of methods, including, electron microscopy, immunohistochemical method, and histochemical method. Further, the diagnosis of small cell carcinoma can be performed on morphologic basis alone, even though the neuroendocrine differentiation can hardly be demonstrated. Patients of ages higher than 65 years, at high TNM stage, with metastatic disease at presentation have a poor survival rate. As well, the clinical treatments, involving radiotherapy, cystectomy, or chemotherapy, have variable success. Literature Cited Devilee, Peter, and Tavassoli, Fattaneh A. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARC Press, 2003. Gray, Winifred. Diagnostic Cytopathology. London: Churchill Livingstone, Elsevier, 2010. Read More