A rational approach to immunohistochemical analysis of malignant lymphomas on paraffin wax sections.
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Diagnosis, Differential↗
Biomedical subjects
S A Pileri
Publications and source records attributed to S A Pileri.
Immunohistochemistry of bone-marrow biopsy.
In a percentage of cases, conventional morphologic evaluation of bone-marrow needle biopsy (BMNB) in insufficient to achieve a firm diagnosis. Under these circumstances, immunohistochemistry plays a basic role, providing an easy and objective key for the interpretation of the pattern observed in most instances. Herein, the authors focus on the technical procedures, which allow extensive application of immunohistochemistry to the study of BMNB, as well as on the panels of antibodies needed for the identification of the most relevant conditions.
Antigens, CD↗
Frequent expression of the NPM-ALK chimeric fusion protein in anaplastic large-cell lymphoma, lympho-histiocytic type.
The revised European-American lymphoma classification recognizes a subtype of anaplastic large-cell lymphoma (ALCL), termed lympho-histiocytic because of its peculiar cytological composition. As in the case of classical ALCL, this tumor usually occurs in young patients and shows an excellent response to chemotherapy, but some authors have suggested that in reality this is a nonanaplastic T-cell lymphoma rich in histiocytes. In this paper, we show that three of five cases of lympho-histiocytic ALCL stain with anti-ALK antibodies and can therefore be presumed to express the chimeric NPM/ALK protein secondary to (2;5) translocation. These findings further support the inclusion of this as a type of ALCL and not among the nonanaplastic peripheral T-cell lymphomas. Furthermore, they indicate that staining for ALK proteins is a powerful tool for the diagnosis of lympho-histiocytic ALCL, the recognition of which may be difficult on morphological grounds.
Adolescent↗
Molecular findings and classification of malignant lymphomas.
We review the problem of lymphoma classification in the light of the Revised European-American Lymphoma (REAL) scheme, recently proposed by the International Lymphoma Study Group (ILSG). The REAL classification is a list of clinicopathologic entities, all well known from the literature, upon which the ILSG members agreed. Although it contains nothing new, for the first time all the elements, including immunophenotype and molecular data, which characterise a given lymphoma entity are considered. This approach corresponds to the need for objective criteria integrating the often puzzling morphologic findings. Furthermore, better knowledge of the molecular events which contribute to tumour development and progression if of paramount importance for the development of more specific and successful therapies. Some relevant molecular findings included in the classification and additional data obtained by the ILSG members following its publication are discussed.
Chromosome Aberrations↗
Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients.
PURPOSE: During the last few years, the application of CD30 monoclonal antibodies has led to the identification of a new lymphoma entity, termed anaplastic large cell lymphoma (ALCL). This tumor includes four distinct histologic subtypes, among which the Hodgkin's-like/Hodgkin's-related one (ALCL-HL) shares morphologic and phenotypic features with Hodgkin's disease (HD). PATIENTS AND METHODS: From September 1988 to October 1993, 90 ALCL patients were treated with third-generation chemotherapy regimens (either vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate with leucovorin, and prednisone [F-MACHOP] or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) during the course of an Italian multicentric randomized trial on high-grade non-Hodgkin's lymphomas (HG-NHL). In particular, 47 patients had ALCL of the common type (ALCL-CT) and 43 ALCL-HL. Null phenotype was the most common (39.8%), while T-cell, B-cell, and hybrid forms accounted for 35.5%, 22.2%, and 2.5%, respectively. RESULTS: Complete remission (CR) was achieved in 66 of 90 (73.5%) patients (33 of 47 [70%] with ALCL-CT and 33 of 43 [77%] with ALCL-HL). The majority of the patients in CR (56.5%) were alive and well at a median follow-up time of 38 months; no significant differences were observed between the two histologic groups, with the rate of complete responders being 49% and 65% in ALCL-CT and ALCL-HL, respectively. The probability of relapse-free survival (RFS), projected at 63 months, was 67% for ALCL-CT and 82% for ALCL-HL. The risk of lower CR and RFS rates was associated with the presence of bulky disease, advanced stage, and B symptoms. CONCLUSION: The data of the present study confirm that ALCL responds to third-generation chemotherapy regimens similarly to other aggressive malignant lymphomas in terms of both CR and RFS rates.
Adolescent↗
Is Hodgkin's disease a unique entity?
The theoretical bases of Hodgkin's disease (HD) have recently been revised in the light of new findings obtained by means of immunohistochemistry and molecular analysis. These findings have questioned the concept that HD is a unique entity and have made the borders between HD and non-Hodgkin's lymphomas unclear. The clinical relevance of nodular lymphocyte predominance HD (LP-HD), the distinction between T-cell rich B-cell lymphoma and diffuse LP-HD, and the relationships between HD and anaplastic large cell lymphoma are reviewed and discussed.
Biomarkers, Tumor↗
Bone marrow findings further support the hypothesis that essential mixed cryoglobulinemia type II is characterized by a monoclonal B-cell proliferation.
One-hundred-sixteen consecutive bone-marrow biopsies were taken from 76 patients with essential mixed cryoglobulinemia type II (type II cryo), whose median follow-up was 97 months. Fifty-four out of fifty-six subjects who underwent ELISA and RIBA tests for HCV, were found to be positive. At conventional light microscopic examination, 64/76 patients showed discrete lymphoid infiltrates consisting of small elements with plasmacytoid differentiation and with frequent paratrabecular location. Thirty-nine biopsies were studied by immunohistochemistry that revealed the B-cell nature of the infiltrates (CD20+, CD45RA+, CD79 alpha+, CD3-, CD45RO-), with demonstrable monotypic Ig light-chain restriction in 22 cases. It is worthy of note that the lymphoid elements usually appeared protected against apoptosis, because of the strong expression of the bcl-2 oncogene product, and provided with a very low proliferative capacity, the Ki-67 index being lower that 3%. The latter findings are in keeping with the indolent behaviour of the clonal lymphoid population observed in type II cryo and allow some speculation as to the need for environmental stimuli for its maintenance as well as further mutagenic events for its eventual transformation into an overt lymphoma.
Adult↗
Anaplastic large cell lymphoma: update of findings.
The problem of anaplastic large cell lymphoma (ALCL) is extensively reviewed by depicting the clinical, pathological and biological characteristics of the four main varieties of ALCL: common, Hodgkin's like/Hodgkin-related, lympho-histiocytic, and giant-cell rich. Special emphasis is given to the differential diagnosis between ALCL Hodgkin like and Hodgkin's disease in the light of possible therapeutical differences.
Genotype↗
Revised European-American Lymphoma Classification.
The recently proposed Revised European-American Lymphoma Classification represents a serious attempt to overcome the controversies that have divided both pathologists and clinicians over the past three decades. It was formulated by 19 experienced hematopathologists, who agreed on a list of clinicopathologic entities, all well known from the literature and daily practice. Compared with previous schemes, the Revised European-American Lymphoma Classification offers the following advantages: 1) it incorporates all nodal and extranodal lymphoid tumors, including Hodgkin's disease; 2) it is histogenetically updated by recognizing new categories (such as the mantle cell category) and grouping tumors that need further validation to be considered as separate entities (eg, diffuse large B-cell lymphomas); 3) it avoids any morphologic grading, the clinical course of lymphomas being influenced by factors other than histology (tumor burden, cell kinetics, apoptotic rate, and so forth) and 4) it includes all molecular data (phenotype, genotype, cytogenetics, and so forth), which can assist in the diagnosis.
Hodgkin Disease↗
Immunohistochemical detection of the multidrug transport protein P170 in human normal tissues and malignant lymphomas.
Two monoclonal antibodies, MRK16 and C219, both directed at the 170 kDa P-glycoprotein multidrug resistance agent, were applied to frozen sections or cytospin preparations from normal human tissues and 60 non-Hodgkin's malignant lymphomas. Adrenal gland, kidney, liver and pancreas were always stained by the reagents, albeit with slightly different patterns. Brain capillaries as well as macrophages and some elements of the bone marrow, peripheral blood, ovarian stroma and colonic, gastric and jejunal mucosa were positive in all examined preparations. There were differences in the staining patterns with the two antibodies. Among the 60 non-Hodgkin's lymphomas, 25 contained a number of positive cells, which ranged from 2% to 100%. No correlation was seen between the expression of P170 and histological type, stage, clinical symptoms or growth fraction. A close relationship was shown between the presence of P170 positive elements and the clinical course of the disease (P less than 0.001).
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Kikuchi's lymphadenitis and HIV infection.
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Adolescent↗
Selection of a panel of monoclonal antibodies for monitoring residual disease in peripheral blood and bone marrow of interferon-treated hairy cell leukaemia patients.
A panel of monoclonal antibodies (mAbs) directed against B-cell and hairy cell leukaemia (HCL)-associated antigens was used to identify residual hairy cells in the peripheral blood and/or bone marrow samples from 20 patients with HCL, following treatment with interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta). In all cases, hairy cells retained their characteristic phenotype, e.g. positivity for CD22, CD11c, CD25, CD32, and the HCL-associated trimeric protein (t-GP) recognized by the mAbs HML-1, B-ly7, LF61 and Ber-Act8. The most specific marker for identifying a small percentage of hairy cells in peripheral blood cytospins, was t-GP. In alkaline phosphatase/anti alkaline phosphatase (APAAP) stained preparations, t-GP+ hairy cells (provided with large cytoplasm and hairy surface) could be usually distinguished from t-GP+ normal lymphocytes (small-sized cells with smooth surface). In doubtful cases the percentage of residual hairy cells could exactly be estimated by double immunofluorescence staining for CD22 (B-cell marker) and t-GP. The rationale of the test is based on the finding that the small percentage (about 1%) of t-GP+ lymphocytes circulating in the peripheral blood of normal individuals are T-cells of the CD8 subset and not B-cells. The best markers for identifying residual hairy cells in routine bone marrow biopsies were CD45RA (mAb 4KB5) and CD20 (mAb L26). Immunohistological labelling was superior to morphological examination in picking up scattered hairy cells in bone marrow biopsies showing either severe hypoplasia or exuberant hyperplasia of normal haemopoietic series.
Antibodies, Monoclonal↗
Malignant lymphoma involving the mandible. Clinical, morphologic, and immunohistochemical study of 17 cases.
We present 17 cases of non-Hodgkin's lymphoma of the mandible, collected over a span of 10 years. Clinically, the patients showed a male:female ratio of 1:2.4 and a mean age of 60.6 years. Swelling was the most common symptom. In 11 of 17 patients, the disease presented in stage I. Radiotherapy alone was employed in 11 patients, in conjunction with chemotherapy in 5 patients, and was preceded by surgery in the remaining case. At this writing ten of the subjects are still alive, five died following progression of the disease, and two were lost during follow-up while in complete remission. Histopathology revealed 15 B-cell lymphomas (1 centroblastic/centrocytic, nine centroblastic, one Burkitt's, two immunoblastic, and two lymphoblastic) and two peripheral T-cell lymphomas (pleomorphic). The above diagnoses were confirmed by immunohistochemical analysis with a wide panel of reagents against fixative-resistant molecules. Our data suggest that (a) lymphomas of the mandible are principally represented by high-grade B-cell varieties (88%); (b) primitive T-cell lymphomas (here documented for the first time) have the same incidence in the mandible as they have in lymph nodes; and (c) immunohistochemistry, besides confirming histogenetic interpretations based on morphologic findings, provides the key to the differential diagnosis from malignant large-cell nonlymphoid tumors.
Adult↗
Posttransplant lymphoproliferative disorder: morphological picture and diagnostic difficulties.
Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of both solid organ and bone marrow transplantation. It includes a wide spectrum of proliferative changes ranging from reactive hyperplasia, borderline lesions to malignant lymphomas. PTLD develops in 1% to 10% of transplant recipients. We present 10 cases of PTLD. Five developed after renal, four after liver, and one after heart transplantation. Among the early lesions, we diagnosed two reactive plasmacytic hyperplasias; one infectious mononucleosis-like PTLD; one polymorphic lesion; and one "mixed" case of plasmacytic hyperplasia in one tonsil with a polymorphic PTLD in the second one. Among the lymphomas, we observed three diffuse large B-cell lymphoma (DLBCL); one mantle lymphoma; and one Hodgkin lymphoma-like PTLD. The morphological pictures of six PTLD cases were typical and posed no diagnostic problems. In the one case of plasmacytic hyperplasia, the lymph node morphology was atypical with atrophy of lymphoid components accompanying plasma cell proliferation. Contrary to a good prognosis of early, reactive PTLD, this patient experienced a rapid course and succumbed to sepsis. The most difficult case was a rare Hodgkin lymphoma-like PTLD, which was diagnosed only by a bone marrow biopsy. Because of its noncharacteristic immunophenotype, it was primarily diagnosed as an anaplastic lymphoma of the T-cell type. After additional immunohistochemical studies (BOB and OCT2), we established the final diagnosis of Hodgkin lymphoma-like PTLD. Due to the increasing number of organ transplantations, doctors of various specialties may encounter PTLD.
Adult↗