e-book Malignant Lymphomas Other than Hodgkin’s Disease: Histology · Cytology · Ultrastructure · Immunology

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The cells grow in a cohesive pattern and often preferentially involve the lymph node sinuses, as well as extranodal sites, such as soft tissue, bone and skin. There is a variable admixture of granulocytes and macrophages. A lymphohistiocytic variant occurs, in which reactive histiocytes predominate and the rare neoplastic cells may be smaller than classic ALCL cells Pileri , and a small cell variant has been described recently, whose relationship to classic ALCL remains to be determined Kinney The majority of the tumours with the morphology described above express one or more T-cell-associated antigens, many express neither T- nor B-cell-associated antigens and in some cases express B-cell antigens.

Several morphological variants of this malignancy such as common type, monomorphic, small cell predominant, lymphohistiocytic, neutrophil rich, and sarcomatoid variants have been described Kadin H and Y blood group antigens have been observed in half the cases Delsol The gene at the 2p23 breakpoint encodes a tyrosine kinase, ALK anaplastic lymphoma kinase. The gene rearranged at 5q35, the nucleophosmin gene NPM encodes a nucleolar phosphoprotein also known as nucleolar protein B23 or numatrin.

Shiota in a screen for aberrant tyrosine kinases in a cell line of Ki-1 anaplastic large-cell lymphoma. True cytogenetic variants represent the rearrangement of one translocation partner with another gene, typically homologous to the usual translocation partner. Examples include the t 8;22 and t 2;8 variants of the t 8;14 q24;q32 , where MYC rearranges with one of the immunoglobulin light chain genes instead the IgH. Several cytogenetic variants of the t 2;5 have been reported. Anaplastic large cell lymphoma ALCL is a rare tumour, but may be diagnosed with increasing frequency as its features are more widely recognized.

There are two major forms of ALCL that should be considered distinct categories: the systemic form, which may involve lymph nodes or extranodal sites, including the skin, but is not localized to the skin, and a primary cutaneous form, without extracutaneous spread at the time of the diagnosis Mason In systemic ALCL, the clinical findings at the onset of disease differ according to histotype.

The common and lympho-histiocytic variants most often present with multiple lymphadenopathies stage III-IV disease and fever Pileri Less frequent findings include mediastinal mass, bulky disease, bone lesions, spleen or skin infiltration, and raised LDH values Pileri Bone marrow is rarely involved and the disease usually spares the central nervous system. A leukemic phase has been reported anecdotally Anderson The primary cutaneous form occurs predominantly in adults, as a solitary, asymptomatic cutaneous or subcutaneous reddish-violet tumour, which is frequently located on upper or lower limbs, can be ulcerated, shows rapid growth, and at times may spontaneously regress.

The ALCL lympho-histiocytic type is more often observed in the first or second decade of life, although it is not exclusive to young people. The primary cutaneous form appears to be indolent and incurable, lacks the t 2;5 p23;q35 and is ALK protein-negative.


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ALK- ALCLs occur in older individuals, without gender predominance, and lower incidence of systemic symptoms and extranodal disease Falini There are two major forms of ALCL: the systemic form, which may involve lymph nodes or extranodal sites, including the skin, but is not localized to the skin, and a primary cutaneous form, without extracutaneous spread at the time of the diagnosis Mason The common and lympho-histiocytic variants most often present with multiple lymphadenopathies, stage III-IV disease and fever Pileri From a morphological point of view, ALCL could be suspected when the tumour is composed of large blastic cells with pleomorphic, often horseshoe-shaped or multiple nuclei with multiple or single prominent nucleoli.

Cytogenetic studies could contribute to diagnosis considering the presence of t 2;5 in several ALCL cases Mason Indirectly, the presence of the fusion has also been detected by demonstration of the ALK portion of the molecule by immunohistochemistry or in situ hybridization. It includes an accurate physical examination, complete haematological and biochemical exams, total-body computerized tomography, gastrointestinal tract examination, and bone marrow aspirate and biopsy. Lymphangiography has been completely replaced by abdominal computerized tomography considering the higher sensitivity of tomography to detect mesenteric nodes and its capacity to show a true estimation of nodes size, which usually are underestimated with lymphangiography.

Laparoscopy with multiple liver biopsies should be done only when there is a strong suspicion of liver involvement in a patient who would otherwise have stage I-II disease.

Anaplastic large cell (CD30+) lymphoma

Staging laparotomy and splenectomy should never be performed in ordinary clinical practice as a routine staging procedure. The major factor that accounts for the limited need for laparotomy is the high yield of information from less morbid procedures and the recognition that precise definition of involvement probably has limited importance in treatment planning for most patients. Under certain circumstances, special procedures are required.


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Although extremely rare, bone lesions should be investigated by skeleton scanning, confirmed by routine X-ray studies, and biopsied if possible. Some particular sites of disease frequently involved by ALCL require special diagnostic procedures, such as gastrointestinal tract radiologic and endoscopic assessment. The staging of stomach and colon-rectum requires gastroscopy with several biopsy samples of macroscopically evident lesions, while the small intestine should be studied with contrasted radiological techniques.

Ultrasonography and magnetic resonance imaging are useful to investigate the involvement of breast, soft tissue, salivary glands or orbits. The Ann Arbor staging system reflects both the number of sites of involvement and the presence of disease above or below the diaphragm. This staging system considers four stage of disease: Stage I: involvement of a single lymph node region I or a single extranodal site IE.

Stage II: involvement of two or more lymph node regions on the same side of the diaphragm II or localized involvement of an extralymphatic site IIE. Stage IV: diffuse or disseminated involvement of one or more extralymphatic organs with or without associated lymph node involvement.


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Localized involvement of liver or bone marrow is also considered stage IV. Patients are divided in two subsets according to the presence A or absence B of systemic symptoms. Even though it is a frequent accompanying symptom, itch should not be considered as a systemic symptom. Restaging should include all the diagnostic procedures positive at time of diagnosis and initial staging.

The cutaneous form or primary ALCL at times spontaneously regresses, perhaps as a result of a suppressive effect of tumour growth by transforming growth factor b. Tumours respond well to local treatment surgery, radiotherapy and are associated with a good prognosis: median survival 42 months Beljaards On the other hand, when ALCL develops in the skin as a secondary form or represents an example of skin involvement in patients with systemic disease, it tends to be quite aggressive.

Lymphomatoid papulosis and regressing atypical histiocytosis are two distinct clinical entities related to cutaneous ALCL. Lymphomatoid papulosis, regressing atypical, and cutaneous ALCL might represent a spectrum of one disease, whose histologic and clinical characteristics depend on the host immune response or the aggressiveness of the neoplastic component Kadin The systemic form of ALCL was long regarded as being a very aggressive, incurable disease.

This was due to the fact that all the studies had been carried out retrospectively and included cases originally diagnosed and treated as non-lymphoid tumours.

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Furthermore, treatment was frequently delayed due to the difficulties in making a definite diagnosis. More recent studies show that primary systemic ALCL, common, and a lympho-histiocytic type are very sensitive to aggressive chemotherapy and achieve the same complete remission and overall survival rates as the other variants of high-grade NHLs.

The serum soluble CD30 levels have been reported as negative prognostic indicators in these patients Zinzani a. Combined treatment with primary systemic conventional-dose anthracycline-containing polychemotherapy which may or may not be followed by radiation therapy is the standard option for patients with primary ALCL. Primary systemic conventional-dose polychemotherapy followed by autologous bone marrow transplantation ABMT is investigational. In these patients, primary systemic conventional-dose anthracycline-containing polychemotherapy is suitable for individual clinical use on a type 3 level of evidence.

Neutrophil-rich Kipositive anaplastic large cell lymphoma presenting as a testicular mass. Mod Pathol ; 9: [ Medline ]. Plasma Cells. Histomorphology of the B-Cell Region. Cytology of Germinal Centers.

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Phases of Germinal-Center Development. Kinetics of Germinal-Center Cells. The Function of Germinal Centers. Histomorphology of the T-Cell Region. Histochemistry of B- and T-Cell Regions.

Multilobated B cell lymphomas. A study of 7 cases

Stationary Elements of the Lymph Node. Reticulum Cells. Histiocytic Reticulum Cell. Fibroblastic Reticulum Cell "Dictyocyte". Interdigitating Reticulum Cell. Sinus Endothelial Cells.

Endothelial Cells of the Marginal Sinus. Endothelial Cells of the Intermediate and Medullary Sinuses. Mast Cells. Historical Review of the Classifications of Lymphomas.

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Some Ideas for a Modern Lymphoma Classification. Incidence of the Different Types of Lymphoma in our Material. Malignant Lymphomas of Low-Grade Malignancy. Malignant Lymphoma, Lymphocytic. Mycosis Fungoides M. Lymphomas of Immunoglobulin-Secreting Cells. Malignant Lymphoma, Plasmacytic Plasmacytoma. Lymphomas of Germinal-Center Cells. Malignant Lymphoma, Centrocytic Centrocytoma.

Malignant Lymphomas Other than Hodgkin’s Disease

Malignant Lymphomas of High-Grade Malignancy. Malignant Lymphoma, Centroblastic. Primary Centroblastic Lymphoma. Secondary Centroblastic Lymphoma. B-Lymphoblastic Lymphoma.

Lymphoblastic, Burkitt Type. T-Lymphoblastic Lymphoma. Lymphoblastic, Convoluted-Cell Type. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.