NHLs are a heterogeneous group of malignancies with >30 entities. Consequently, the clinical presentation can be very diverse, varying from acute presentation in aggressive lymphomas to asymptomatic in more indolent disease.

Diagnosis of NHL is based on history, physical examination, laboratory investigations, imaging (computed tomography [CT]/positron emission tomography [PET]), tissue biopsy, and cell markers obtained from immunohistochemical, flow cytometric, and cytogenetic testing.

Pathological evaluation remains the most specific and sensitive test for diagnosis but may be difficult in some complex cases.

NHL may mimic many other conditions and can be difficult to distinguish from inflammation, benign hyperplasia, carcinomas, germ cell tumours, or melanoma.

An additional opinion from an expert haematopathologist may be necessary, especially when clinical history does not fit the pathological diagnosis, or in cases of difficult histological diagnoses such as:

  • Cases with features of both diffuse large B-cell lymphoma (DLBCL) and Hodgkin's disease

  • Cases with features of both DLBCL and Burkitt's lymphoma

  • Differentiating chronic lymphocytic leukaemia (CLL) versus mantle cell lymphoma

  • Differentiating high-grade follicular lymphoma versus DLBCL

  • Cases involving T-cell lymphomas.

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