Carl D. Winberg

Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases.

A clinicopathologic analysis of 16 cases of multicentric angiofollicular lymph node hyperplasia (MAFH) was performed. Histologically, the disease was characterized by recognizable lymph node architecture that was at least partially intact, by paracortical hyperplasia with prominent vascular proliferation, and by numerous evenly distributed, apparently benign germinal centers of various types, usually including some typical hyaline-vascular centers. At the onset of the disease, 12 patients had the plasma cell (PC) type of MAFH, three patients had the hyaline-vascular (HV) type, and one patient presented with PC and HV types at separate sites. Transitions between the PC and HV types were observed in two cases. Immunologic studies demonstrated polyclonal populations of plasma cells in the lymph nodes of all patients and the absence of suppressor T lymphocytes in the one patient tested. Clinically, the patients had constitutional symptoms, multicentric lymphadenopathy, hepatosplenomegaly in many cases, and abnormal laboratory findings, including anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. The 16 patients were placed in four different clinical groups based on presentation and course: stable disease, chronic relapsing disease, aggressive disease, and development of malignant lymphoma. Ten of the 16 patients died (median survival, 26 months; range, eight to 170 months). Multicentric angiofollicular lymph node hyperplasia appears to be a variant of classic angiofollicular lymph node hyperplasia (Castlemans disease) and is associated with significant morbidity and mortality.

Further Evidence That Malignant Angioendotheliomatosis Is an Angiotropic Large-Cell Lymphoma

Malignant angioendotheliomatosis is a rare, generally fatal disease characterized by a multifocal proliferation of neoplastic mononuclear cells within the lumens of small blood vessels. Although the disease primarily involves the vasculature of the skin and central nervous system, vascular involvement of other organs may occur and may produce a variety of clinical findings. Some early investigators concluded that malignant angioendotheliomatosis was a neoplasm of endothelial cells, but recently others have suggested that it is of hematopoietic origin. We have studied three patients with the disease and have characterized the immunophenotype of the neoplasm on cryostat-cut fresh-frozen tissues. A detailed antigenic phenotyping of neoplastic lymphoid cells showed that one patient had the immunophenotype T11+, Leu-1+, Leu-3+, Leu-2+, B1-, B2-, SIg-, LN1-, LN2-, the predominant phenotype for peripheral T-cell lymphoma; the others had T11-, Leu-1-, Leu-3-, Leu-2-, B1+, B2+, SIg+, LN1+, LN2+, consistent with a B-cell-derived lymphoma. On the basis of our results, we suggest that angiotropic (intravascular) large-cell lymphoma would be more appropriate than malignant angioendotheliomatosis as a name for this disease.

Malignant lymphoma, intermediate lymphocytic type: A clinicopathologic study of 42 cases

A clinicopathologic analysis of 42 cases of non‐Hodgkins lymphoma of the intermediate lymphocytic type (ILL) having morphologic features between those of well‐differentiated (WDLL) and poorly differentiated lymphocytic lymphoma (PDLL) is presented. In lymph node sections, ILL was characterized by a diffuse proliferation consisting predominantly of small lymphoid cells with slightly irregular or indented nuclei. A mixture of lymphoid cells with entirely round nuclei and lymphoid cells with angulated and cleaved nuclei was also present, but each of these two cell populations did not comprise more than 30% of the total. The median age of the patients was 65 years, and the male‐to‐female ratio was 5:1. Generalized lymphadenopathy was evident in 74% of the patients, and B symptoms were presented in 36%. Peripheral blood involvement was present at the onset of disease in 21% of the patients, and the bone marrow was involved by lymphoma in 76% of those examined. Five percent of the patients had Stage I disease, 24% had Stage III disease, and 71% had Stage IV disease. Ninety‐three percent of the patients received multiagent chemotherapy and 41% achieved a complete remission. The overall median survival was 31 months. Clinical features which appeared to influence survival adversely included the presence of B symptoms (P = 0.007), age greater than 70 years (P = 0.09), an absolute lymphocyte count above 5000/mm3 (P = 0.05), and anemia (P = 0.09). Achievement of a complete remission influenced survival favorably (P = 0.02). Pathologic features which appeared to influence survival included sinus obliteration, which had an adverse effect (P = 0.05), and the presence of residual germinal centers which had a favorable effect (P = 0.06). Patients with 0–5 mitoses/10 high power fields (HPF) had a significantly longer survival than those with more than 20 mitoses/10 HPF (P = 0.02), while those with 6–20 mitoses/10 HPF had an intermediate survival. The clinical and pathological features of patients with ILL suggest that this entity is closely related to PDLL and should be distinguished from WDLL.

Monocytoid B-Cell Lymphoma Clinicopathologic Study of 21 Cases of a Unique Type of Low-Grade Lymphoma

The morphologic and immunologic features of three cases of an unusual and distinct B‐cell lymphoma were recently described and termed monocytoid B‐cell lymphoma (MBCL) because of the striking resemblance of the neoplastic cells to reactive monocytoid B‐lymphocytes. The morphologic spectrum and the clinical behavior of MBCL were investigated in a series of 21 patients. This study indicates that patients with MBCL usually present with lymphadenopathy and Stage I or II disease. MBCL also occurs at extranodal sites including the salivary gland. Because four of the patients with MBCL had Sjögrens syndrome with characteristic laboratory profiles, these results raise the possibility that there may be a relationship between MBCL and Sjögrens syndrome. Eight patients were male and 13 female (M:F = 1:1.6), and MBCL primarily involved the elderly (median age, 66 years). The most striking clinical findings were high percentages of complete remissions and long survival times indicating that MBCL is a low‐grade lymphoma. Of 21 patients investigated, 18 were in complete remission at the time of completion of this study. Two patients died with the disease and one was lost to follow‐up. Patients with localized MBCL may have a better survival rate than those with generalized disease. Like other low‐grade lymphomas, MBCL can progress to a higher grade lymphoma of large cell type. Unlike other low‐grade lymphomas, in MBCL splenomegaly, bone marrow involvement, and leukemic conversion are uncommon.

Antigenically defined subgroups of lymphoblastic lymphoma: relationship to clinical presentation and biologic behavior

A large panel of monoclonal antibodies and polyclonal antisera were used to ascertain the immunophenotypic characteristics of 36 lymphoblastic lymphomas (LBL). Results showed that this group of lymphomas have significant immunologic heterogeneity. Of the 36 cases, 33 were positive for T‐cell antigens; among these, 22 cases were classified as T‐cell LBL (TLBL, Group 1) based on their expression of T‐cell‐restricted and T‐cell‐associated antigens, and five expressed the common acute lymphoblastic leukemia antigen in addition to T‐cell‐associated antigens (Group 2). Six cases showed strong reactivity with anti‐Leu‐11 antibody, which defines a specific subtype of lymphocytes considered to have a natural killer (NK) function (Group 3). Two additional cases had a “pre‐B” cell phenotype (Group 4), as determined by reactivity with BA‐1 and BA‐2 monoclonal antibodies, which react with immature and pre‐B‐lymphocytes. The neoplastic cells in the remaining case showed monoclonal surface membrane immunoglobulin of the IgMD heavy chain and kappa light chain type (Group 5). Despite immunophenotypic heterogeneity, the morphologic features were essentially similar in all cases. When the clinical features for each immunologic group were compared, however, two statistically significant findings resulted: (1) the frequency of mediastinal masses was highest in TLBL (Group 1, P < 0.01), and (2) the male–female ratio was significantly lower in patients with LBL expressing NK‐associated antigens (Group 3) than in the other groups of patients (P < 0.01). Our data indicate that LBL can be divided into several immunologic subtypes; larger, prospective clinicopathologic studies are required to determine the clinical significance of the immunophenotypic classifications of LBL.

Acral lentiginous melanoma A clinicopathologic study of 36 patients

Acral lentiginous melanoma (ALM) is a distinct variant of malignant melanoma with a predilection for the soles, palms, and nail beds. This melanoma has characteristic histologic features, and its biologic behavior is similar to that of nodular melanoma. It occurs predominantly in the sixth, seventh, and eighth decades of life, with a peak incidence in the seventh decade for males and in the sixth decade for females. Diagnosis of ALM during the radial growth phase is often difficult, and it may not be recognized initially, but treatment in this phase offers an excellent prognosis. There is a high incidence of regressive changes and desmoplasia in ALM; these changes, together with the anatomic peculiarities of nail beds, palms, and soles as compared with other skin areas, make it difficult to determine the Clarks level and to measure the depth of invasion. Wide local excision with lymph node dissection is recommended for subungual melanomas measuring more than 1.00 mm and for lesions showing severe regression. Volar melanomas less than 1.00 mm deep and those in the radial growth phase with minimal invasion require only wide local excision. Amputation of digits and lymph node dissection are recommended for subungual melanomas, if the melanomas exhibit the vertical growth phase. If there is only radial growth without regressive changes, wide local excision is adequate. Patients with metastasis to lymph nodes at the time of diagnosis usually have shorter survival times than do those without lymph node involvement (P = 0.027). Cancer 52:161‐168, 1983.

Morphologic criteria for the differentiation of follicular lymphoma from florid reactive follicular hyperplasia: a study of 80 cases.

A study was made of 80 patients whose lymph nodes were characterized by the presence of follicles throughout the lymph node. The patients were divided into two groups on the basis of the clinical follow‐up information. The first group consisted of 20 patients who were alive and disease‐free at the end of five years without therapy. The patients in this group were classified as having florid reactive follicular hyperplasia (FRFH). The second group of 60 patients had progressive, recurrent, clinically active disease and were classified as having follicular lymphoma (FL). Forty‐six were dead of active disease, and 14 were alive with disease. Various morphologic parameters were evaluated at low and high magnification, and statistical comparisons were made between FRFH and FL. Although several criteria were helpful in distinguishing FRFH from FL, the single most valuable criterion was the type of pattern encountered. Follicles of variable size and shape lying adjacent to each other throughout the lymph node without or with very little intervening tissue are diagnostic of FL. This pattern was evident in 85% of the FL cases, but was not observed in any of the cases of FRFH.

Pathology of autoimmune myelofibrosis: A report of three cases and a review of the literature

We identified 3 patients with autoimmune myelofibrosis (AM) lacking American Rheumatism Association criteria for systemic lupus erythematosus (SLE). They had 1 or 2 cytopenias and lacked serologic evidence for SLE. Autoimmune features included psoriatic arthritis and positive direct Coombs test (DCT) result, DCT-positive autoimmune hemolytic anemia, and synovitis with polyclonal hypergammaglobulinemia. Bone marrow biopsy specimens from each patient were evaluated by routine morphologic and immunohistochemical examination. They demonstrated marked hypercellularity (2 cases) or hypocellularity (1 case), moderate erythroid hyperplasia (all cases) with left-shifted maturation (2 cases), intrasinusoidal hematopoiesis (all cases), slightly to moderately increased megakaryocytes (2 cases), and grade 3 to 4 reticulin fibrosis (all cases). All lacked basophilia, eosinophilia, bizarre megakaryocytes, clusters of megakaryocytes, and osteosclerosis. Mild to moderate bone marrow lymphocytosis was noted in all cases. In 2 cases, increased small T cells and B cells formed nonparatrabecular, loose aggregates. AM is a clinicopathologic entity that may lack features of SLE. Loose aggregates of bone marrow T and B lymphocytes and the absence of morphologic and clinical features of myeloproliferative disease or low-grade lymphoproliferative disease are clues that distinguish AM from better known causes of bone marrow fibrosis.

Monocytoid B lymphocytes: Their relation to the patterns of the acquired immunodeficiency syndrome (AIDS) and AIDS-related lymphadenopathy

It was shown recently that monocytoid cells express B-cell-restricted antigens and polyclonal surface immunoglobulins, and the term monocytoid B lymphocytes (MBL) has thus been offered as a more appropriate designation. Although most commonly seen in toxoplasmic lymphadenitis, MBL have been observed in a variety of reactive and neoplastic conditions involving lymph nodes. In the present study MBL were found in 17 of 22 lymph nodes from 20 patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related lymphadenopathy. In all 17 samples, the MBL were found in lymph nodes with florid reactive follicular hyperplasia, and they were geographically close to the hyperplastic lymphoid follicles. However, MBL were not detected in lymph nodes showing involuted follicles or lymphocyte depletion. The disappearance of MBL apparently parallels the progressive involution of secondary follicles. Leu-3+/Leu-2+ (T-helper/T-suppressor) ratios were studied in 14 lymph node cell suspension samples and ten peripheral blood samples. The lymph node Leu-3+/Leu-2+ ratios were significantly lower in AIDS-related lymphadenopathy than in non-AIDS-related reactive follicular hyperplasia (P less than 0.001); the peripheral blood ratios were decreased in nine of the ten cases. The diminished T-helper status in patients with AIDS and AIDS-related lymphadenopathy may be relevant to the immunopathogenesis of follicular involution and, indirectly, to the disappearance of MBL.

Follicular (nodular) lymphoma during the first two decades of life: A clinicopathologic study of 12 patients

Twelve patients who developed non‐Hodgkins lymphoma with a follicular pattern during the first two decades of life were studied. Eight had the poorly differentiated lymphocytic type; the remaining four had the “histiocytic” type. Eleven of the 12 patients were male. Nine were asymptomatic, and eight had lymphadenopathy in the head and neck region. Comparison of ages revealed the extent of disease tended to be localized (Stages I and II) in the pediatric (<16 years old) patients (83%) and generalized in the adolescent‐young adult (16–19 years old) patients (83%). Often patients treated with chemotherapy and/or radiotherapy, eight achieved complete remissions that lasted 3–58 months (median, 17.5 months). Five are still in remission; three have relapsed. Seven are alive 12–120 months from diagnosis (median, 48 months); six have no clinical evidence of disease. The remaining five patients died two to 164 months after diagnosis (median, 13 months). Three of the four patients who died with lymphoma had diffuse “histiocytic” lymphoma demonstrated at autopsy examination. Poor prognostic factors included 1) failure to achieve a complete remission following initial therapy; 2) extranodal disease (with the exception of the poorly differentiated lymphocytic type involving the spleen and liver); 3) development of diffuse “histiocytic” lymphoma. Follicular lymphoma occurring in the second decade of life has a biologic behavior similar to follicular lymphoma in adults.