Neoplastic Conditions

Malignant lymphomas: Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) are the two broad categories of malignant lymphoid neoplasms in the WHO consensus classification. The NHLs are further subclassified as neoplasms of the B, T and NK cells. The disease entities are recognised on the basis of available information using morphology, immunophenotyping, genetics and clinical features.

The WHO classification includes both lymphomas and leukaemias since both solid and circulatory phases are recognised in many lymphoid neoplasms. The practical approach to diagnosis is based on cell size, which correlates with clinical features and response to treatment. Thus, "low-grade lymphomas" present as disseminated disease, respond to treatment and have a median survival in years.

Prognosis may also be related to stage of disease, i.e., the number of regional lymph node groups involved, their anatomical site (viz peripheral versus mediastinal or retroperitoneal) and the presence and extent of extranodal disease.

Up to 90% of the NHLs are B cell neoplasms. The clinical and pathological features of the most frequent "low-grade" small B cell lymphomas are listed in Table 44.3.

Marginal zone lymphoma: accounts for 7-8% of lymphoid neoplasms. It is rare in the nodes but nearly always presents at extranodal sites as MALTomas, e.g., stomach, salivary gland and thyroid.

"High-grade" diffuse large B cell lymphomas: are aggressive and present as nodal, extranodal, localised or disseminated disease. Distinctive clinical variants are mediastinal large B cell lymphoma, primary effusion lymphoma and intravascular lymphoma. Morphologic variants are centroblastic, immunoblastic, plasmablastic, T cell rich and anaplastic. The clinical relevance of these is debatable and they are not subdivided in the WHO classification. Early-stage disease is chemoresponsive and potentially curable. Tumour cells are usually CD20 and CD79a positive with a high Ki67 proliferation index.

Burkitt's lymphoma: is a high-grade tumour of medium-sized rapidly proliferating B cells (Ki67~100%). The major clinical subtypes include endemic, sporadic and immunodeficiency related. The type of tumour seen in the West shows greater pleomorphism than the Burkitt's lymphoma described in Africa and has been termed Burkitt-like.

T/NK cell neoplasms: are relatively uncommon and account for approximately 12% of the lymphoid neoplasms in the West. The clinical features are important for subtyping, as the morphology, immunophenotype and genetics are not absolutely specific.

Table 44.3. Low-grade small B cell non-Hodgkin's lymphomas

Chronic Lymphocytic Leukaemia

Mantle Cell Lymphoma Follicle Centre Cell Lymphoplasmacytic Lymphoma Lymphoma

Clinical

«22% of NHL. Disseminated at

Rare under 20yrs. presentation.

Disseminated at M protein, presentation. Hyperviscosity,

Disseminated disease Disseminated at at presentation. presentation.

Biologically aggressive. Median survival 2-5yrs.

cryoglobulinemia

Architecture

Pale staining pseudofollicles. Background diffuse small lymphocytes.

Diffuse, less commonly Closely packed Diffuse, Interfollicular. nodular proliferation. follicles, absent mantles, loss of polarity.

Cytology

Paraimmunoblasts, Small-to-medium-sized Centroblasts, Small B lymphocytes.

Prolymphocytes. lymphocytes with slight centrocytes. Atypia. Plasmacytoid

Small lymphoid cells nuclear irregularity. May have signet lymphocytes with clotted chromatin Scattered histiocytes ring cells.

minimally larger than and hyalinised vessels mature lymphocytes. common. Blasts in blastoid variant.

Immunohistochemistry CD5, CD20, CD23,

CD5, Cyclin D1, CD20, CD10, bcl2, VS38 positive.

CD43 positive. CD10, bcl6 positive. CD43+/-. CD5, CD10,

CD23, bcl6 negative. CD5/43 negative. CD23 negative

CD43 positive. CD10, Cyclin D1 negative

Cytogenetics Trisomy 12 in 20%

The commonest subtypes are peripheral T cell lymphoma, not otherwise specified, and anaplastic large cell lymphoma.

Peripheral T cell lymphoma, NOS: is a heterogeneous group of neoplasms with a broad cyto-logical spectrum. The tumour cells are small-to-medium sized with irregular nuclei and pleomorphic cells that may be Reed-Sternberg-like. CD3 and other T cell antigens are positive and aberrant antigen expression is common. TCR genes are rearranged but there are no markers of monoclonality.

Anaplastic large cell lymphoma: most frequently occurs in the first three decades of life. The tumour cells have pleomorphic horseshoe-shaped nuclei, abundant cytoplasm, and are referred to as "hallmark cells". The tumour grows often within sinuses in a cohesive manner. T cell antigens, EMA, cytotoxic granule proteins, ALK-1 and CD30 are positive. Ninety per cent of cases have clonal rearrangement of TCR genes. ALK-1 expression is due to t (2:5) (q23; 35). Variant translocations involving ALK-1 and other partner genes on chromosomes 1, 2, 3 and 17 also occur. Overall five-year survival rate is 80% in ALK-1-positive patients while ALK-1 negativity is prog-nostically adverse.

Hodgkin's lymphoma: accounts for 30% of all lymphomas. The new WHO classification divides Hodgkin's lymphoma into two major subtypes.

- HL, nodular sclerosis, grade I and II.

- HL, lymphocyte-rich.

- HL, mixed cellularity.

- HL, lymphocyte depleted.

• Nodular lymphocyte-predominant HL (NLPHL - a B cell lymphoma).

The clinical and pathological features are detailed in Table 44.4.

Plasma cell neoplasms: include myeloma and its variants, plasmacytoma, immunoglobulin deposition diseases, osteosclerotic myeloma and heavy chain diseases, all of which have a clonal proliferation of immunoglobulin-secreting, terminally differentiated B cells, i.e., plasma cells and plasmacytoid lymphocytes.

Metastatic tumours: lymph nodes are common sites of tumour metastasis, which may be the presenting feature. Nodal spread is common in carcinomas, malignant melanomas and germ cell tumours, and uncommon in sarcomas and mesotheliomas.

Lymphomas mimicking carcinomas: anaplastic large cell lymphoma, diffuse large B cell lymphoma with sclerosis, large cell lymphoma with sinusoidal growth pattern, nodular sclerosing Hodgkin's lymphoma and signet ring lymphoma.

Metastatic carcinoma mimicking lymphoma: nasopharyngeal/lymphoepithelial carcinoma and lobular carcinoma breast.

Cystic metastases in cervical lymph nodes: commonly due to papillary thyroid carcinoma and squamous cell carcinoma.

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