Is it cancer?

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Although there are some exceptions, benign tumours consist of a uniform population of cells that resemble their normal non-neoplastic counterpart whilst malignant tumours generally show variability. In benign tumours cells are small and uniform, with small nuclei and a low nuclear:cytoplasmic (N:C) ratio. Nucleoli may be absent or nuclei may contain 1-2 small nucleoli. When in aggregates the cell arrangement is orderly and neat. Malignant tumours are recognised by identifying cellular, nuclear and cytoplasmic criteria of malignancy: Abnormal location for that cell type e.g. metastatic carcinoma cells should not be present in a lymph node; macrocytosis and karyomegaly with anisocytosis and anisokaryosis; cell clusters may be chaotic and disordered with cell or nuclear moulding; increased N:C ratio; large nucleus and sparse; bi- and multinucleation – anisokaryosis within one cell is especially significant; multiple nucleoli or a single large nucleolus; coarsely stippled to clumped nuclear chromatin; frequent/ abnormal mitoses; increased cytoplasmic basophilia and/or abnormal cytoplasmic vacuolation or granulation, or excessive secretory product. The shape and arrangement of cells will help identify the ‘family’ of cells: Epithelial cells are columnar, cuboidal, roundish or polygonal and in cohesive clusters. Mesenchymal cells are oval to spindle shaped and seen individually or in loose aggregates, sometimes with a swirling pattern, with poorly defined cell borders. Round cells are discrete. The quantity and appearance of the cytoplasm distinguishes lymphoid cells, plasma cells, histiocytic cells and mast cells.

Staging determines the extent of disease in cancer patients, to inform treatment decisions. Recommended staging is strongly influenced by the diagnosis and likely behaviour of the tumour: a diagnosis is essential. Full staging is most appropriate for high grade tumours, and in older patients (identifying comorbidities) or before invasive/expensive treatments. Cytology is particularly useful for superficial masses and those accessible by ultrasound guidance. Carcinomas and round cell tumours tend to exfoliate well, sarcomas not. Primary tumour extent is assessed clinically and by imaging. Carcinomas, mast cell tumours, and malignant melanomas tend to metastasise by the lymphatic route, requiring assessment of locoregional lymph nodes. The closest node (moving from peripheral to central) is often likely to be the draining node, but lymphangiography can identify unexpected draining nodes in high grade tumours. Identifying and sampling these nodes leads to better staging. Imaging of retropharyngeal, axillary, medial iliac and inguinal nodes by ultrasound or CT is useful: CT allows imaging of sacral nodes e.g. in anal sac adenocarcinoma patients. FNA has a variable rate of false negatives in different tumours: in particular, FNA may be insensitive to oral melanoma metastases. For distant metastases, cytology is especially useful for assessing splenic and hepatic nodules.

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