Australian Society of CytologyCase of the Month
August 2003 - Answer and Discussion
Small cell carcinoma of lung.
Answer
The Wang biopsy specimen is abundantly cellular and well preserved. The background consists of blood and cellular debris. The specimen contains isolated cells, syncytial aggregates, small cellular sheets and some rosette formations. The small malignant cells have a high nuclear/cytoplasmic ratio with nuclei that are irregular and have indented nuclear membranes. These nuclei are hyperchromatic with fine chromatin and small to inconspicuous nucleoli. The cytoplasm is scant and delicate. Other diagnostic features on the prepared smears include nuclear moulding, crush artefact, mitoses and necrosis.
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| H&E stain | H&E stain | H&E stain |
The bronchial biopsy sections demonstrate the infiltration of small malignant cells, which have hyperchromatic nuclei, small nucleoli and scant cytoplasm. The biopsies show marked crush artefact. Nuclear moulding is highlighted at the periphery of the sections where crush artefact is minimal.
DISCUSSION
Small cell carcinoma is a highly malignant, rapidly growing neoplasm (Demay 1996). The male/female occurrence ratio is 4:1, and it is said to be strongly associated with cigarette smoking (Sternberg 1999). Small cell carcinoma is usually centrally located and metastasizes to the hilar and mediastinal lymph nodes. Surgical therapy is generally ineffective, with some patients responding to aggressive combination chemotherapy and radiotherapy. The overall 5-year survival rate remains at less than 5%, as the tumour is usually widely disseminated at time of diagnosis (Demay 1996).
The interpretation of bronchial specimens can be difficult, as often the specimens show abundant crush artefact. In such cases, observation of the small, well-preserved areas will suffice for an accurate diagnosis. The cytological preparations often provide for an accurate diagnosis in distinguishing small cell carcinoma and non-small cell carcinoma (Sternberg 1999).
Small cell carcinoma is classified into three morphological types. The first is pure small cell carcinoma, which includes the classic oat cell and intermediate cell subtypes as defined previously by the World Health Organisation. The other morphological types are considered variants of pure small cell carcinoma. Combined small cell carcinoma, includes squamous or adenocarcinoma and mixed small cell carcinoma, consists of small/large cell types. Small cell carcinoma is part of a spectrum of poorly differentiated neuroendocrine tumours that can show a range of cell sizes and can be combined with cells showing squamous or glandular differentiation.
Small cell carcinoma usually demonstrates features of neuroendocrine origin immunocytochemically, including neuron-specific enolase, neurofilament proteins, synaptophysin, Leu-7 and sometimes chromogranin or keratin. Ultrastructurally, the tumour cells shows small desmosomes and cellular processes, sometimes with macrotubules and neurosecretory granules characteristic of neuroendocrine differentiation.
The diagnosis of small cell carcinoma is usually a contraindication to surgery, therefore diagnosis by the least invasive method is important. Wang needle biopsy with bronchial biopsy is accurate and reliable, however it is important to differentiate this tumour from other small cell tumours such as lymphoma or poorly differentiated squamous cell carcinoma (Demay 1996).
References
- De May, R 'The Art and Science of Cytopathology', ASCP 1996.
- Sternberg, S 'Diagnostic Surgical Pathology', Third edition, Lippincott Williams & Wilkins 1999
