Small cell bronchogenic carcinoma: a distinct clinicopathologic entity.

Since small cell carcinoma is a treatable disease, with surgery being beneficial in a few cases and with chemotherapy, radiotherapy, and immunotherapy contributing to prolonged survival in patients with inoperable disease, it is essential that the clinical and pathologic features of small cell carcinoma be quickly recognized in a newly presenting patient so that appropriate therapy may be offered.     

T-cell/histiocyte-rich large B-cell lymphoma: a distinct clinicopathologic entity.

PURPOSE: Although it has proven difficult to delineate diagnostically reproducible and clinically relevant subgroups, the heterogeneity of diffuse large B-cell lymphomas (DLBCL) is widely acknowledged. In 1992, we reported on six cases that suggested that large B-cell lymphoma rich in stromal histiocytes and T cells may be identified as a distinct clinicopathologic entity within DLBCL. PATIENTS AND METHODS: An integrated clinicopathologic study of 40 cases of this DLBCL subtype is presented. RESULTS: Distinguishing a DLBCL rich in histiocytes and reactive T cells, designated T-cell/histiocyte--rich large B-cell lymphoma (THR-BCL), may be justified from a clinical point of view. The disease typically affects middle-aged male patients who usually present with advanced-stage disease that is not adequately managed with current therapeutic strategies. Whereas proliferation fraction and p53 overexpression, in addition to the clinical variables incorporated in the International Prognostic Index (IPI), significantly correlate with response to treatment and survival in a univariate analysis, only the IPI score identifies relevant prognostic THR-BCL subpopulations in a multivariate model. The morphologic and immunophenotypic profile of the neoplastic B cells in THR-BCL suggests that they may originate from a germinal center ancestor. CONCLUSION: THR-BCL constitutes a distinct clinicopathologic entity that is characterized by an aggressive behavior. Experimental therapeutic strategies may be indicated to obtain a more favorable response to treatment in this disease.     

Multilobated non-Hodgkin's lymphoma. A clinicopathologic entity

Multilobated non-Hodgkin's lymphomas (NHL) have recently been recognized as an NHL variant. During a period of 10 years we observed 30 individuals with NHL in which more than 30% of the malignant cells had a characteristic multilobation. The immunologic phenotype was determined in 14 of these cases. One was of T-cell lineage, and the others exhibited B-lymphoid markers. Sixty-eight percent of the patients presented with extranodal localizations. In the clinical follow-up a complete remission was observed in 78% of patients with a mean duration of 37 months (range, 5 to 120 months). The actuarial survival after 5 years was 45%. From these data we conclude that multilobated NHL are comparable to diffuse, large cleaved-cell NHL of an intermediate grade malignancy according to the Working Formulation or are comparable to the diffuse centrocytic-centroblastic NHL according to the Kiel classification. The neoplastic cells are to be considered as variants of follicle center cells, but the clinicopathologic correlation indicates that multilobated NHL represent a distinct nosologic entity.     

Infantile histiocytosis X.

Skin biopsies and a lymphnode of three children with infantile Histiocytosis-X (Letter-Siwe Disease) were studied with enzymehistochemical and sheep-erythrocyte rosetting techniques. The majority of cells making up the infiltrates of skin and lymphnode showed rather weak acid phosphatase and nonspecific esterase activity but considerable leucyl-beta-naphtylamidase activity. Sheep-erythrocyte rosetting techniques performed on frozen sections indicated the presence of receptors for the Fc fragment of IgG, but no receptors for C3 could be demonstrated. Cells with the same enzymehistochemical characteristics could be found in thymus-dependent areas of normal spleen, of normal and reactive lymphnodes and in thymic medulla but not in B-cell areas or thymic cortex. It is suggested that Histiocytosis-X cells belong to the Mononuclear Phagocyte System and that they are related to or identical with cells normally present in the thymus dependent areas of the lymphoid tissue involved with the functioning of cell-mediated immunity.     

Malignant histiocytosis

The clinical features, therapy, and hospital course of ten consecutive patients with malignant histiocytosis (MH) are presented. The value of bone marrow aspiration for the diagnosis is discussed. The patient's performance status as described in this report by the organ dysfunction score may predict survival and response to chemotherapy. The literature on chemotherapy in this disease is reviewed. Combination chemotherapy may be the best approach to treatment, but there is little experience with single agents. There is a great need for better characterization of the malignant cell in this disorder.     

Malignant histiocytosis and related tumors. A clinicopathologic study of 42 cases using cytological, histochemical and ultrastructural parameters

Light and electron microscopical, immunohistochemical and clinical characteristics in 42 cases of malignant neoplasms, arising from true histiocytes, are described. These were separated in a lymphoma-like subtype, called true histiocytic lymphoma (29 patients) and a disseminated variant, called malignant histiocytosis (9 patients). In addition 4 related histiocytic tumors are discussed, including 2 tumors arising from interdigitating cells. Sinus pattern and cytologic features, especially 'window' nuclei, are emphasized as diagnostic criteria. Erythrophagocytosis was not a constant finding. Electron microscopic features, presence of acid phosphatase, acid alpha-naphthylacetate esterase, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, Ia-antigen and absence of B- and T-cell markers, were important in establishing the histiocytic nature or excluding a non-histiocytic tumor. A distinct male predominance existed (male:female = 2.5:1) with a higher relapse free period in females (p = 0.032). A high number of mitotic figures appeared to be a favourable sign, p = 0.020 and 0.019, for remission rate and relapse free period respectively. The degree of cell differentiation and the immunohistochemical pattern did not show a correlation with remission and relapse free period. Extranodal involvement and the presence of short profiles of endoplasmic reticulum were prognostically unfavourable signs. True histiocytic lymphomas showed a higher remission rate (p = 0.041) and relapse-free period (p = 0.017) than malignant histiocytosis.     

Malignant histiocytosis X. Report of a rapidly fatal case in an elderly man

A 71-year-old white man developed an increasing number of 1-to-10 mm, erythematous nodules, many with central ulceration, most prominent on the head and trunk. Biopsy of a nodule showed infiltration of the dermis and epidermis by large cells with multilobulated nuclei and numerous mitoses. Electron microscopy showed that most tumor cells contained Langerhans' cell granules. Immunohistochemical studies demonstrated a pattern of antigen expression similar to that of Langerhans' cells including Ia and Leu-6 (T6) antigens. Chest x-ray showed diffuse pulmonary infiltration and similar tumor cells were present in the sputum and urine. He developed increasing dyspnea and jaundice despite chemotherapy, and died 6 months after the onset of the disease. Autopsy showed massive tumor infiltration of the lungs, liver, spleen, and lymph nodes, and focal involvement of the myocardium, skin and bladder. Clinical and cytologic features indicated this case to be a rare example of highly malignant histiocytosis X in an elderly man.     

EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement.

PURPOSE: Epstein-Barr virus (EBV) is detected in a substantial subgroup of gastric adenocarcinomas worldwide. We have previously reported that these EBV-positive gastric carcinomas carry distinct genomic aberrations. In the present study, we analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features to determine whether they constitute a different clinical entity. PATIENTS AND METHODS: Using a validated polymerase chain reaction/enzyme immunoassay-based prescreening method in combination with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor cells of 7.2% (n = 41) of the gastric carcinomas from the Dutch D1D2 trial (N = 566; mean follow-up, 9 years). EBV status was correlated with clinicopathologic features collected for the Dutch D1D2 trial. RESULTS: EBV-positive gastric carcinomas occurred significantly more frequently in males (P <.0001) and in younger patients (P =.012). Most were of the intestinal type according to the Laurén classification (P =.047) or tubular according to the WHO classification (P =.006) and located in the proximal part of the stomach (P <.0001). A significantly lower tumor-node-metastasis system-stage (P =.026) was observed in the patients with EBV-carrying carcinomas, which was solely explained by less lymph node (LN) involvement (P =.034) in these cases. In addition, a better prognosis, as reflected by a longer disease-free period (P =.04) and a significant better cancer-related survival (P =.02), was observed for these patients, which could be explained by less LN involvement, less residual disease, and younger patient age. CONCLUSION: EBV-carrying gastric adenocarcinomas are a distinct entity of carcinomas, characterized not only by unique genomic aberrations, but also by distinct clinicopathologic features associated with significantly better prognosis.     

Histiocytosis X. Langerhans' cell histiocytosis

Histiocytosis X is a complex and poorly understood entity. Nevertheless, it would appear as if certain themes are found recurrently throughout the literature dealing with this disease and a review of them serves as a useful summary. 1. Problems with Nomenclature. To name or categorize a disease based on end-organ pathology is generally not clinically useful, but this is what we have done with histiocytosis X. It has caused substantial confusion among physicians and patients alike concerning diagnosis, prognosis, and treatment. Further attempts at improving the nosology of this disease will not be useful unless those new names also reflect scientific advances in our understanding of etiology, pathogenesis, and therapy. 2. Identification of the Langerhans' Cell as the Consistent Pathognomonic Cell in the Lesions of Histiocytosis X. Although the Langerhans' cell was identified more than a century ago, it has only recently been recognized as the cell that proliferates in this disease. Nevertheless, several important questions remain regarding the relationship of the Langerhans' cell to histiocytosis. Foremost among these questions is whether the Langerhans' cell is a truly normal Langerhans' cell, responding appropriately to immune system signals, or if it is an abnormal variant, possibly even neoplastic. 3. Recognition that Immune System Dysfunction Is a Critical Part of Histiocytosis X. The immune system is the focus of most recent clinical research. Results of these studies are obviously important with regard to both the biology and management of this disease. 4. Histiocytosis X Is an Extremely Heterogeneous Clinical Disorder. As mentioned before, the term histiocytosis X was originally intended by Lichtenstein to describe a pathologic, and not clinical, entity. It is rare to find two patients with this disease who are exactly alike. To make matters even more confusing, the disease includes both infants with disseminated fatal disease as well as middle-aged adults with solitary bony lesions. 5. The Disease Requires Improved Therapy, but it Is a Difficult Setting in which to Perform Clinical Studies. Improved therapy is required in patients with this disease, especially those with the disseminated form. But it will be difficult to develop improved therapy until definitive answers are provided to some of the basic questions of etiology and pathogenesis. Unfortunately, these clinical studies are not readily available because of the rare occurrence of this disease and its extreme clinical heterogeneity.(ABSTRACT TRUNCATED AT 400 WORDS)     

So-called histiocytosis X and malignant histiocytosis

A retrospective study of 12 cases of so called histiocytosis-X and 3 cases of malignant histiocytosis was done. It was possible to establish the differences in clinical, morphologic and cytochemical findings of both diseases. The diagnosis of histiocytosis-X can be confirmed by multinucleated histiocytes interrupted by eosinophils and plasmacells. The histopathology of malignant histiocytosis is different and is characterized by atypical histiocytes. Erythrophagocytosis throughout the tissues is seen. Typical histochemistry (acid phosphatase and naphtol-AS-acetat-esterase) findings are also helpful for diagnosis. The treatment of both diseases should be continued at least six months after disappearance of clinical apparent lesions. Combination chemotherapy with vinblastine and prednisone is suggested. In cases of histiocytosis-X in isolated lesions curettage or irradiation may be adequate. Long term remissions and presumed cures of histiocytosis-X are possible in over 70% of the cases. A strict correlation between the prognosis and the degree of involvement is confirmed. Even in cases of malignant histiocytosis, previously reported as rapidly fatal disease, combination chemotherapy may produce complete long term remissions.     

B-lineage lymphoblastic lymphoma is a clinicopathologic entity distinct from other histologically similar aggressive lymphomas with blastic morphology.

BACKGROUND: The authors present clinical, histopathologic, and immunophenotypic data regarding B-lineage lymphoblastic lymphoma (B-LBL), a rare entity that has not been extensively studied. To emphasize some of its unique clinical characteristics, the authors compare B-LBL with a group of histologically similar, very aggressive lymphomas, T-lineage lymphoblastic lymphoma (T-LBL) and the blastoid variant of mantle cell lymphoma (BVMCL); all were evaluated concurrently. METHODS: Clinical data were obtained on 29 patients with very aggressive lymphomas (12 B-LBLs, 10 T-LBLs, and 7 BVMCLs) from whom paraffin-embedded material was available. The diagnoses were confirmed on review of the hematoxylin and eosin-stained slides and the immunophenotype data. RESULTS: The mean age of patients with B-LBL was 39 years. Patients presented with both lymph node and extranodal disease, although involvement of the mediastinum and bone marrow was infrequent. Four were Stage I, 3 were Stage II, 2 were Stage III, and 3 were Stage IV. B-LBL patients were treated primarily with cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP), and one patient underwent allogeneic bone marrow transplantation. The mean follow-up time was 30 months. Seven of 11 had no evidence of disease at 48 months, whereas 4 patients were dead of disease at 5.6 months. The overall median survival was 24 months. The clinical characteristics of B-LBL patients differed significantly from those of T-LBL patients; there was more frequent bone marrow and mediastinal involvement in T-LBL cases (P = 0.03 and 0.04, respectively). T-LBL patients were also less likely to achieve a complete remission than B-LBL patients (P = 0.02). The mean age of BVMCL patients significantly exceeded that of B-LBL patients (P = 0.03). CONCLUSIONS: The authors believe that the distinction of B-LBL from its histologic mimics, T-LBL and BVMCL, has important clinical implications. Patients with B-LBL present differently from those with the other very aggressive lymphomas studied, and they achieve complete remissions more often than T-LBL patients.     

Syncytial variant of nodular sclerosing Hodgkin's disease. A new clinicopathologic entity

The clinicopathologic and histopathologic features of an unusual morphologic variant of nodular sclerosing Hodgkin's Disease (HD) termed the syncytial variant has been reported recently. We report eight new cases with this unique morphology, identified by reviewing the histopathology of 58 patients with nodular sclerosing HD treated in our institute between 1982 and 1988. The clinicopathologic and histopathologic data of these cases are reported and we emphasize this new entity and the difficulties encountered in the morphologic diagnosis. All of the eight patients had a difficult initial clinical course, and were in a clinically advanced stage of the disease at the time of diagnosis. We cite a statistical comparison of the clinical features of the different forms of nodular sclerosing HD.     

Peripheral T-cell lymphoma. A clinicopathologic study of a morphologically diverse entity

We analyzed the clinicopathologic features of 13 patients with immunologically confirmed peripheral T-cell lymphoma. The lymphomas were classified into poorly differentiated lymphocytic, mixed cell, and large cell types. Marked morphologic heterogeneity was noted within the mixed cell and large cell categories, and the various subtypes are described. Twelve of the 13 patients received multiagent chemotherapy. Only three of the nine patients with poorly differentiated or mixed cell lymphomas achieved a complete remission, and the median survival for this group was 11 months. In contrast, all three of the treated patients with large cell lymphomas achieved a complete remission, two of whom are alive without disease (14 and 29 months, respectively). Classification of peripheral T-cell lymphomas into lymphocytic, mixed cell, and large cell types, as well as further subclassification within the heterogeneous groups, is suggested so that pathologic features of prognostic significance can be identified.     

Malignant histiocytosis in children

The analysis of peculiarities of clinical course and morphology of malignant (acute) histiocytosis in 50 pediatric patients made a case for identification of the disease as separate pathology of histiocytic sarcoma type. Clinical course features include: lymphadenopathy, involvement of bones and--less frequently--lungs, skin and subcutaneous fat, marked fever and weight loss. Cytologic and histologic examination show polymorphic tumor cells of varying degree of differentiation, with blasts predominating. Well-developed Golgi complex, presence of lysosomes, phagosomes and erythrophagocytosis are among the characteristic ultrastructural features of the disease.