Атлас по гематологии (английский язык)

74 Abnormalities of the White Cell Series

Chronic Lymphocytic Leukemia (CLL) and Related Diseases

A chronic lymphadenoma, or chronic lymphocytic leukemia, can sometimes be clinically diagnosed with some certainty. An example is the case of a patient (usually older) with clearly enlarged lymph nodes and significant lymphocytosis (in 60% of the cases this is greater than 20 000/µl and in 20% of the cases it is greater than 100 000/µl) in the absence of symptoms that point to a reactive disorder. The lymphoma cells are relatively small, and the nuclear chromatin is coarse and dense. The narrow layer of slightly basophilic cytoplasm does not contain granules. Shadows around the nucleus are an artifact produced by chromatin fragmentation during preparation (Gumprecht’s nuclear shadow). In order to confirm the diagnosis, the B-cell markers on circulating lymphocytes should be characterized to show that the cells are indeed monoclonal. The transformed lymphocytes are dispersed at varying cell densities throughout the bone marrow and the lymph nodes. A slowly progressing hypogammaglobulinemia is another important indicator of a B-cell maturation disorder.

Transition to a diffuse large-cell B-lymphoma (Richter syndrome) is rare: B-prolymphocytic leukemia (B-PLL) displays unique symptoms. At least 55% of the lymphocytes in circulating blood have large central vacuoles. When 15–55% of the cells are prolymphocytes, the diagnosis of atypical CLL, or transitional CLL/PLL is confirmed. In some CLL-like diseases, the layer of cytoplasm is slightly wider. B-CLL was defined as lymphoplasmacytoid immunocytoma in the Kiel classification. According to the WHO classification, it is a B-CLL variation (compare this with lymphoplasmacytic leukemia, p. 78). CLL of the T-lymphocytes is rare. The cells show nuclei with either invaginations or well-defined nucleoli (T-prolym- phocytic leukemia). The leukemic phase of cutaneous T-cell lymphoma (CTCL) is known as Sézary syndrome. The cell elements in this syndrome and T-PLL are similar.

Fig. 23 CLL. a Extensive proliferation of lymphocytes with densely structured ! nuclei and little variation in CLL. Nuclear shadows are frequently seen, a sign of the fragility of the cells (magnification #400). b Lymphocytes in CLL with typical coarse chromatin structure and small cytoplasmic layer (enlargement of a section from 23 a, magnification #1000); only discreet nucleoli may occur. c Slightly eccentric enlargement of the cytoplasm in the lymphoplasmacytoid variant of CLL.

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

Table 9 Staging of CLL according to Binet (1981)

AHb " 10.0 g/dl, normal thrombocyte count $ 3 regions with enlarged lymph nodes

Characteristics of CLL

Age of onset: Mature adulthood

Clinical presentation: Gradual enlargement of all lymph nodes, usually moderately enlarged spleen, slow onset of anemia and increasing susceptibility to infections, later thrombocytopenia

CBC: In all cases absolute lymphocytosis; in the course of the disease Hb ", thrombocytes ", immunoglobulin "

Further diagnostics: Lymphocyte surface markers (see pp. 68ff.); bone marrow (always infiltrated); lymph node histology further clarifies the diagnosis

Differential diagnosis: (a) Related lymphomas: marker analysis, lymph node histology; (b) acute leukemia: cell surface marker analysis, cytochemistry, cytogenetics (pp. 88ff.)

Course, therapy: Individually varying, usually fairly indolent course; in advanced stages or fast progressing disease: moderate chemotherapy (cell surface marker, see Table 7)

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

Fig. 24 Lymphoma of the B-cell and T-cell lineages. a Prevalence of large lymphocyteswithclearlydefinednucleoliandwidecytoplasm:prolymphocyticleukemiaof theB-cellseries(B-PLL). b Thepresenceoflargeblasticcells(arrow)inCLLsuggesta rare transformation (Richter syndrome). c The rare Sézary syndrome (T-cell lymphoma of the skin) is characterized by irregular, indented lymphocytes. d Prolymphocytic leukemia of the T-cell series (T-PLL) with indented nuclei and nucleoli (rare). e Bone marrow in lymphoplasmacytic immunocytoma: focal or diffuse lymphocyte infiltration (e.g., 1), plasmacytoid lymphocytes (e.g., 2) and plasma cells (e.g., 3). Red cell precursors predominate (e.g., basophilic erythroblasts, arrow).

77

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

78 Abnormalities of the White Cell Series

The pathological staging for CLL is always Ann Arbor stage IV because the bone marrow is affected. In the classifications of disease activity by Rai and Binet (analogous to that for leukemic immunocytoma), the transition between stages is smooth (Tables 8 and 9).

Lymphoplasmacytic Lymphoma

The CBC shows lymphocytes with relatively wide layers of cytoplasm. The bone marrow contains a mixture of lymphocytes, plasmacytic lymphocytes, and plasma cells. In up to 30% of cases paraprotein is secreted, predominantly monoclonal IgM. This constitutes the classic Waldenström syndrome (Waldenström macroglobulinemia). The differential diagnosis may call for exclusion of the rare plasma cell leukemia (see p. 82) and of lymphoplasmacytoid immunocytoma, which is closely related to CLL (see p. 74).

Characteristics

Lymphoplasmacytoid immunocytoma: This is a special form of B- CLL in which usually only a few precursors migrate into the bloodstream (a lesser degree of malignancy). A diagnosis may only be possible on the basis of bone marrow or lymph node analysis.

Lymphoplasmacytic lymphoma: Few precursors migrate into the bloodstream (i.e., bone marrow or lymph node analysis is sometimes necessary). There is often secretion of IgM paraprotein, which can lead to hyperviscosity.

Further diagnostics: Marker analyses in circulating cells, lymph node cytology, bone marrow cytology and histology, and immunoelectrophoresis. Plasmacytoma cells migrate into the circulating blood in appreciable numbers in only 1–2% of all cases of plasma cell leukemia. Therefore, paraproteins must be analyzed in bone marrow aspirates (p. 82).

Facultative Leukemic Lymphomas

(e.g., Mantle Cell Lymphoma and Follicular Lymphoma)

In all cases of non-Hodgkin lymphoma, the transformed cells may migrate into the blood stream. This is usually observed in mantle cell lymphoma: The cells are typically of medium size. On close examination, their nuclei show loosely structured chromatin and they are lobed with small indentations (cleaved cells). Either initially, or, more commonly, during the course of the disease, a portion of cells becomes larger with relatively enlarged nuclei (diameter 8–12 µm). These larger cells are variably “blastoid.” Lymphoid cells also migrate into the blood in stage IV follicular lymphoma.

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.