Diffuse large B-cell lymphoma showing an interfollicular pattern of proliferation: a study of the Osaka Lymphoma Study Group.

AIMS: Diffuse large B-cell lymphoma (DLBCL) usually proliferates effacing lymph follicles. In occasional cases, tumour cells show an interfollicular pattern of proliferation preserving lymph follicles. The aim was to analyse clinicopathological findings in DLBCL showing an interfollicular pattern of proliferation to determine whether this type of lymphoma is a distinct entity of DLBCL. METHODS AND RESULTS: Clinicopathological findings in 12 cases of DLBCL showing an interfollicular pattern of proliferation [interfollicular group (IF)] were examined and compared with those in 30 cases of DLBCL with ordinary morphology [control group (CG)]. IF showed a significantly lower lactate dehydrogenase level and International Prognostic Index scores than CG (P = 0.023 and P < 0.01, respectively). The frequency of localized disease, clinical stage 1 and 2, in IF was higher than that in CG (P = 0.016). A morphologically polymorphous pattern of proliferation was found in seven of 12 cases (58.3%) in IF, which was higher than that in CG, five (16.7%) of 30 cases (P < 0.01). Clonality analysis with the polymerase chain reaction method revealed that all 11 IF cases examined showed a monoclonal pattern. Immunohistochemically, the majority (11 of 12) of IF cases showed a non-germinal centre B-cell phenotype and the frequency was higher than that in CG (P = 0.021). CONCLUSION: Diffuse large B-cell lymphoma with an interfollicular pattern of proliferation shows distinct clinical and pathological findings from ordinary DLBCL.

Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells.

CDCP1, a novel stem cell marker, is expressed in hematopoietic cell line K562 but not in Jurkat. When CDCP1 promoter was transfected exogenously, Jurkat showed comparable promoter activity with K562, suggesting that the factor to enhance transcription was present but interfered to function in Jurkat. The reporter assay and si-RNA-mediated knockdown experiment revealed that zfp67, a zinc-finger protein, enhanced CDCP1 transcription. Amount of zfp67 in Jurkat was comparable with K562, but chromatin immunoprecipitation showed that zfp67 bound to CDCP1 promoter in K562 but not in Jurkat. There are CpG sequences around the promoter of CDCP1, which were heavily methylated in Jurkat but not in K562. Addition of demethylating reagent to Jurkat induced CDCP1 expression, and increased the zfp67 binding to CDCP1 promoter. Among normal hematopoietic cells such as CD34+CD38- cells, lymphocytes and granulocytes, inverse correlation between proportion of methylated CpG sequences and CDCP1 expression level was found. Demethylation of CpG sequences in lymphocytes, in which CpG sequences were heavily methylated, induced CDCP1 expression and its expression level further increased through zfp67 overexpression. The methylation of DNA appeared to regulate the cell-type-specific expression of CDCP1 through the control of interaction between chromatin DNA and transcription factors.

Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer.

BACKGROUND: Dexamethasone, a synthetic glucocorticoid, has clinical benefit in patients with hormone-refractory prostate cancer (HRPC), but the mechanisms responsible for its effects are unknown. The nuclear factor-kappaB (NF-kappaB)-dependent cytokine interleukin (IL) 6 (IL-6) is thought to stimulate growth of HRPC. Because dexamethasone interferes with NF-kappaB activation, we determined whether dexamethasone inhibits prostate cancer growth by working through the glucocorticoid receptor (GR) to interfere with NF-kappaB-IL-6 pathway. METHODS: Three human prostate cancer cell lines (DU145, PC-3, and LNCaP) were assessed for GR expression and responsiveness to dexamethasone. Levels of GR, NF-kappaB, and the cytoplasmic NF-kappB inhibitor IkappaBalpha were determined by western blotting and of IL-6 by enzyme immunoassay. The subcellular localization of NF-kappaB was analyzed by immunofluorescence. The effects of dexamethasone (thrice weekly injections of 1 microg/mouse) on DU145 xenografts in nude and severe combined immunodeficient (SCID) mice were evaluated. GR expression in human prostate cancers was assessed by immunohistochemistry. All statistical tests were two-sided. RESULTS: Dexamethasone dose dependently decreased GR levels and inhibited the growth of DU145 and PC-3 but not LNCaP cells (DU145 cells, P< .001; PC-3 cells, P = .009). Dexamethasone increased IkappaBalpha protein levels and the cytosolic accumulation of NF-kappaB in DU145 cells and decreased secreted IL-6 levels to 37 pg/mL (95% confidence interval [CI] = 33 pg/mL to 41 pg/mL), compared with 164 pg/mL (95% CI = 162 pg/mL to 166 pg/mL) secreted by ethanol-treated control cells. Dexamethasone inhibited the growth of DU145 xenografts in nude (P = .006) and SCID (P = .026) mice without affecting GR levels. Eight of 16 human prostate cancers expressed GR at high levels (>or=30% GR-positive cells). CONCLUSION: Dexamethasone inhibited the growth of GR-positive cancers, possibly through the disruption of the NF-kappaB-IL-6 pathway.

Frequent mutations of Fas gene in thyroid lymphoma.

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling through binding of Fas ligand. Mutation of the Fas gene results in accumulation of lymphoid cells and thus might contribute to lymphomagenesis. Thyroid lymphoma (TL) is supposed to arise from active lymphoid cells formed in the preceding autoimmune chronic lymphocytic thyroiditis (CLTH). We examined the open reading frame of Fas cDNA in 11 cases of CLTH and 26 cases of TL. These patients were admitted to the hospital with varying degrees of goiter. All of the CLTH patients were female, with median age of 65 years, and all but five cases of TL were female, with median age of 61 years. Mutations of the Fas gene were detected in 3 (27.3%) of 11 cases of CLTH and 17 (65.4%) of 26 of TL. The Fas mutations comprised 18 frameshift, 3 missense, and 1 nonsense mutation. Frameshift mutations were caused by insertion of 1 bp (A) at nucleotide 1095 in 10 cases and by lack of exon 8 in 8 cases. The insertion of 1 bp (A) at nucleotide 1095 has never been reported in other kinds of malignancies. Thus, this might be unique in TL and CLTH and might be mutational hotspots in these diseases. All mutations occurred in the cytoplasmic region (death domain) known to be involved in the apoptotic signal transduction and thus could be loss-of-function mutations. These findings suggested that accumulation of lymphoid cells in CLTH with Fas mutation provides a basis for development of TL.

Specific c-kit mutations in sinonasal natural killer/T-cell lymphoma in China and Japan.

Sinonasal lymphoma is one of the constituents of lethal midline granuloma, which is a clinical term for progressive, destructive lesions affecting the midline of the face. The majority of sinonasal lymphomas, especially those showing polymorphous patterns of proliferation and thus termed polymorphic reticulosis, recently were categorized as sinonasal natural killer/T-cell lymphomas. They are more prevalent in Asia than Europe or North America and are associated with EBV infection. Twenty-three cases with sinonasal natural killer/T-cell lymphomas were collected from two high-incidence regions: Beijing, China (14 cases) and Osaka, Japan (9 cases). c-kit mutations were analyzed on paraffin-embedded specimens by PCR-single-strand conformation polymorphism followed by direct sequencing; the c-kit proto-oncogene encodes a receptor of tyrosine kinase, which plays an important role in the regulation of normal and neoplastic hematopoiesis by the interaction with its specific ligand, termed stem cell factor. Twelve single nucleotide substitution mutations were seen in 23 cases. Ten of 14 Chinese cases (71.4%) had mutations at exon 11 or exon 17, whereas only two of nine Japanese cases (22.2%) had mutations, showing a significant difference in frequency between Chinese and Japanese cases. Furthermore, seven of eight mutations (92%) in exon 17 occurred at codon 825 and three of four mutations (75%) in exon 11 occurred at codon 561. Such a specificity has not been reported before, and these results, taken together, suggest that location-specific differences in etiological factors cause specific mutations in c-kit gene.

Frequent p53 mutations at dipyrimidine sites in patients with pyothorax-associated lymphoma.

A high incidence of non-Hodgkin's lymphoma of the pleural cavity has developed in Japanese patients with long-standing pyothorax (38 years on average) resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. Patients with pyothorax-associated lymphoma (PAL) have long been exposed to antituberculous drugs, antibiotics, bacterial or viral products, and frequent diagnostic radiation for the confirmation of pneumothorax and pyothorax. We analyzed p53 mutations on paraffin-embedded specimens from 21 patients with PAL by PCR-single-strand conformational polymorphism followed by direct sequencing. An unusually high frequency of p53 mutations (14 of 21 cases, 67%) was detected in the PAL specimens, and mutations consisted of 13 nucleotide substitutions and 1 deletion. Furthermore, 10 of 13 substitutions (77%) occurred at dipyrimidine sites (CC:GG to CT:GA substitution). Such specificity has not been reported, except for solar light-related skin cancer and AIDS-related lymphoma in some parts. An UV light mimetic agent may be produced in the long history of chronic inflammation in tuberculosis or immunodeficient patients.

Moloney murine leukemia virus infection accelerates lymphomagenesis in E mu-bcl-2 transgenic mice.

E mu-bcl-2 transgenic mice bearing the bcl-2 proto-oncogene linked to the immunoglobulin enhancer (E mu) sporadically develop B or T cell lymphomas after a long latent period. To identify genes that play important roles in development of lymphoid malignancies, proviral insertional mutagenesis with Moloney murine leukemia virus (MMuLV) was carried out in two lines of transgenic mice expressing the bcl-2 gene primarily in B or T cells. MMuLV infection of non-transgenic mice induced primarily mature T cell lymphomas. By contrast, infection of newborn E mu-blc-2 mice with the virus accelerated lymphomagenesis, and nearly all of the mice eventually succumbed to clonal pre-B, B, or mainly immature T cell lymphoma, indicating the active contribution of the bcl-2 gene in lymphomagenesis. Southern blot analysis of tumor DNA from MMuLV-infected transgenic mice revealed a proviral insertion at the c-myc gene in 26% (9/35) of tumors, at the pim-1 gene in 6% (2/35) and at the pim-2 (recently renamed tic-1) gene in 23% (8/35). Some tumors carried two activated oncogenes. No insertion was detected at the bmi-1 gene. These data suggest the usefulness of this transgenic system for analysis of lymphomagenesis involving the activated bcl-2 gene.

Role of an immunosuppressive cytokine, interleukin-10, in the development of pyothorax-associated lymphoma.

Malignant lymphoma frequently develops in the pleural cavity of the patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most of PALs are diffuse lymphoma of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses Epstein-Barr virus nuclear antigen 2 (EBNA2) that works as a target molecule for cell-mediated immune response. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF) beta 1 mRNA, however, neither expressed latent TGF beta binding protein (LTBP) mRNA at detectable level by Northern blot analysis. Because TGF beta expresses its functions in cooperation with LTBP, the biological functions of TGF beta 1 could be negligible. Neither cell lines expressed EBV BCRF1 mRNA at detectable level, a viral gene product which is partly homologous to human IL-10 and shares biological activities of IL-10. Since OPL-1 shows weaker proliferative activity than OPL-2 and expresses viral antigens, the production of an immunosuppressive cytokine, IL-10, might contribute to the development of overt lymphoma. The present study suggested that immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.

Appearance of a different clone of Epstein-Barr virus genome in recurrent tumor of pyothorax-associated lymphoma (PAL) and a mini-review of PAL.

A case of pyothorax-associated lymphoma (PAL) is reported. A 76-year-old Japanese man developed a lymphoma in the pleural cavity after 46 years duration of pyothorax due to pulmonary tuberculosis. The histologic diagnosis of biopsy specimen was diffuse large cell lymphoma of B cell type. The lymphoma cells contained the monoclonal Epstein-Barr virus (EBV) determined by the analysis of terminal repeat of EBV genome and expressed EBV nuclear antigen 2 and latent membrane protein 1 (LMP1). He received antineoplastic chemotherapy and was induced to complete remission (CR). After 19 months of CR, the lymphoma developed again in the thoracic wall. Histopathology and immunohistochemical phenotypes of recurrent tumor were almost the same as those of the primary tumor with the exception of a little more frequent expression of LMP1. The EBV genome in lymphoma cells was monoclonal, however, the clone was different from that of the primary tumor. After antineoplastic chemotherapy, minor EBV-positive clones in primary lymphoma might survive and develop into recurrent tumor. These results suggest that the PAL starts as poly- or oligoclonal proliferation of B lineage cells. This poly- or oligoclonality of PAL at the initial stage may suggest underlying immunosuppressive conditions in the development of PAL.

The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes.

The Wilms' tumor gene, WT1, is a tumor marker for leukemic blast cells. The WT1 expression levels were examined for 57 patients with myelodysplastic syndromes (MDS) (refractory anemia (RA), 35; RA with excess of blasts (RAEB) 14; RAEB in transformation (RAEB-t), six; and MDS with fibrosis, two) and 12 patients with acute myeloid leukemia (AML) evolved from MDS. These levels significantly increased in proportion to the disease progression of MDS from RA to overt AML via RAEB and RAEB-t in both bone marrow (BM) and peripheral blood (PB). WT1 expression levels in PB significantly correlated with the evolution of RAEB or RAEB-t to overt AML within 6 months. Therefore, WT1 expression levels in PB were superior to those in BM for early prediction of the evolution to AML by means of quantitation of the WT1 expression levels. Furthermore, WT1 expression in PB of patients with overt AML evolved from MDS was significantly decreased by effective chemotherapy or allogeneic stem cell transplantation and became undetectable in long-term survivors. These results clearly showed that WT1 expression levels are a tumor marker for preleukemic or leukemic blast cells of MDS and thus reflect the disease progression of MDS. Therefore, monitoring of WT1 expression levels has made continuous assessment of the disease progression of MDS possible, as well as the prediction of the evolution of RAEB or RAEB-t to overt AML within 6 months. The results also showed that quantitation of WT1 expression levels is useful for diagnosis of minimal residual disease of MDS with high sensitivity, thus making it possible to evaluate the efficacy of treatment for MDS.

Increased expression of renin in chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is the main cause of renal transplant failure in the first decade posttransplant. The precise pathogenetic mechanism for CAN is not completely understood. A possible role of renin-angiotensin system for CAN has been suggested through clinical observations that angiotensin-converting enzyme inhibition and angiotensin II receptor blockers prevent CAN. METHODS: Distribution of renin-positive cells in allograft biopsy specimens was examined immunohistochemically in 23 renal transplant recipients diagnosed with CAN Biopsy specimens obtained from seven recipients with stable renal function were examined as controls. Histologic evaluation was performed based on the Banff 97 classification. RESULTS: Renin-positive cells were found in the juxtaglomerular apparatus (JGA) adjoining the afferent arterioles in both groups. When the number of renin-positive cells in JGA was defined as a renin index, it was significantly higher in the CAN than the control group (P = .007). There was no significant difference in age, interval between transplantation and biopsy, and blood pressure between groups. Only a significantly higher serum creatinine was found in the CAN group. CONCLUSIONS: The increased renin-positive cells in JGA suggest a significant role of the intrarenal renin-angiotensin system activation in the development of CAN.

Lectin histochemistry of malignant fibrohistiocytic tumors.

The staining pattern by Ricinus communis agglutinin (RCA), a lectin used as a good marker for histiocytes, in 24 cases with malignant fibrous histiocytoma (MFH) was studied and compared with that of 12 cases of fibrosarcoma (FS). In 20 (83%) of 24 cases of MFH, varying degrees of RCA binding were observed, whereas only four (33%) of 12 cases of FS were positive. RCA-positive FS included three cases with infantile FS and one adult case with post-radiation FS. Eight adult patients with FS were entirely negative. This positivity rate of RCA binding in MFH was much higher than those of antisera against lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin previously reported. Seven MFH patients with focal aggregation of RCA-positive benign-appearing (reactive) histiocytes died earlier than the other patients with only scattered RCA-positive histiocytes; 5-year survival rates were 32% and 69%, respectively (p less than 0.05). These findings suggest that RCA reactivity can be used as a potential diagnostic and prognostic marker for MFH.

Renal neoplasias in patients receiving dialysis and renal transplantation: clinico-pathological features and p53 gene mutations.

BACKGROUND: In Japan, the relative risk for renal cell carcinoma (RCC) in renal transplants was about 80-fold higher than that in the general population. Depressed immune surveillance due to the use of immunosuppressive agents was considered to cause cancer. Before renal transplantation, a vast majority of patients received hemodialysis, a known causative factor for acquired cystic disease of kidney (ACDK). Because ACDK is also considered to predispose to RCC, at least two risk factors for cancer accumulate in renal transplants. METHODS: In our study, clinicopathological features together with p53 gene mutations were analyzed in 218 patients with RCC: 22 received dialysis followed by renal transplantation, 39 received dialysis alone, and 157 sporadic RCC. P53 mutations were analyzed on DNA extracted from paraffin-embedded specimens with use of single strand conformation polymorphism, followed by direct sequencing. RESULTS: RCC in transplants shared several clinicopathological features with those in dialysis patients, which included small size and multiplicity of tumor, relatively high frequency of presence of ACDK, and papillary type of RCC. p53 gene mutations were infrequent in RCC of any clinical setting. CONCLUSIONS: Atrophic kidney at the end-stage of renal failure and under dialysis have lesions of ACDK that might predispose to RCC in dialysis and transplant patients.

Clinicopathological study of livers from brain-dead patients treated with a combination of vasopressin and epinephrine.

Studies were made on the pathological lesions and biochemical indices of the livers of 22 patients in whom normal hemodynamics was maintained for 0-48 days after brain death by administration of vasopressin and epinephrine. Thirty-one specimens of liver tissues were obtained by percutaneous biopsy or at autopsy. The degrees of central venous congestion, central fibrosis, focal fibrosis, fatty metamorphosis, piecemeal necrosis, periportal fibrosis, and intrahepatic cholangitis in livers on various days after brain death were compared with those on the day of brain death (day 0). Central venous congestion was extensive on days 0-4, significantly less on days 5-14, and then again extensive on days 15-48. Central fibrosis and focal fibrosis showed no remarkable change during the 48-day period. Fatty metamorphosis, piecemeal necrosis, and periportal fibrosis showed no significant changes until day 16, but spread extensively on days 40-48. Intrahepatic cholangitis was scarcely observed on day 0 but began to increase after day 3, and spread extensively after day 5. The level of serum glutamic pyruvic transaminase did not increase in most patients until day 15. The mean value of prothrombin activity also did not decrease until day 15. However, the mean value of serum alkaline phosphatase increased gradually after day 3, and was correlated with cholangitis. The present study showed that during prolonged hemodynamic maintenance of brain-dead patients, pathological lesions did not spread or diminished and that biochemical indices did not become worse, or improved, in the first 2 weeks, except for increases in cholangitis and the serum alkaline phosphatase level.

Dedifferentiation of adenoid cystic carcinoma: report of a case implicating p53 gene mutation.

Adenoid cystic carcinoma is an indolent tumour with an unfavorable long-term prognosis. Dedifferentiation of adenoid cystic carcinoma, which is associated with an accelerated clinical course, has recently been described. We report a case with immunohistochemical and molecular workup to elucidate the likely mechanism of dedifferentiation. The patient, a 64-year-old woman, developed dedifferentiated adenoid cystic carcinoma of the submandibular gland ab initio, accompanied by cervical lymph node metastasis. Histologically, the low-grade adenoid cystic carcinoma merged gradually into an extensive dedifferentiated component that was composed of solid sheets and cords of anaplastic tumor cells with focal gland formation. Immunohistochemically, the dedifferentiated component, but not the adenoid cyst carcinoma component, showed strong overexpression of p53 protein and cyclin D1, as well as a higher Ki67 index. Molecular study confirmed the presence of p53 gene mutation selectively in the dedifferentiated component, suggesting a pivotal role of p53 gene alteration in the dedifferentiation process of adenoid cystic carcinoma.

Primary lymphoma of the brain developing in a boy after a 5-year history of encephalitis: polymerase chain reaction and in situ hybridization analyses for Epstein-Barr virus.

A 7-year-old boy presented with headache, vomiting, fever, epileptic seizure, and a left hemiparesis. Computed tomography revealed low-density areas in the left frontal lobe and right occipital lobe. Incisional biopsy of the right occipital lesion showed a diffuse and laminar destruction accompanied by microglial reaction in the cortex. An encephalitis of unknown etiology was suspected without data on viral titers in the serum and cerebrospinal fluid. Two months later right hemiparesis and ataxia appeared that were alleviated by prednisolone. Thereafter, similar symptoms repeatedly appeared, but disappeared after treatment with prednisolone. Approximately 5 years later, hemiparesis recurred: computed tomography revealed an 8 x 5 cm mass in the right lobe. A brain biopsy revealed non-Hodgkin's lymphoma of diffuse large, predominantly non-cleaved cell type of B-cell nature. The patient died 1 week after the surgery. The first biopsy specimen (taken at 7 years of age) did not contain Epstein-Barr virus genomes even when examined by polymerase chain reaction. The polymerase chain reaction and in situ hybridization techniques on the second biopsy specimens (taken at 12 years of age) revealed the Epstein-Barr virus sequences in the nuclei of diffuse large cell lymphoma. These findings suggested that the Epstein-Barr virus infection occurring between the first and second biopsies played an etiologic role in the pathogenesis of the brain lymphoma.

P-glycoprotein expression in soft-tissue sarcomas.

Multidrug resistance (MDR) is an important problem in chemotherapy for neoplastic disease. In humans. MDR is mainly mediated by P-glycoprotein (P-gp) a product of the MDRI gene, which acts as a transmembrane protein pump and eliminates chemotherapeutic agents from the cells. Expression of P-gp was immunohistochemically studied by using two monoclonal antibodies, JSB-1 and C-219, on paraffin-embedded sections from 55 patients with soft-tissue sarcoma. The histological diagnosis of tumors was malignant fibrous histiocytoma in 24 cases, liposarcoma in 9, synovial sarcoma in 7, malignant neurogenic tumors in 6, leiomyosarcoma in 5, others in 4. The histological grade was determined on the basis of criteria previously proposed by us. Out of 55 cases, 34 (62%) were positive for P-gp expression. There was a significant difference in P-gp expression between high-grade (90%) and intermediate and low-grade tumors (46%) (P < 0.005). Tumors expressing P-gp had a less favorable prognosis than P-gp-negative tumors in the high- and intermediate-grade tumors. The current study demonstrated that the estimation of P-gp expression could be used to select appropriate therapeutic modalities.

Epstein-Barr virus in malignancies in renal transplant recipients in Japan.

A role for Epstein-Barr virus (EBV) in the development of malignancies including lymphomas, and carcinoma of the stomach, nasopharynx, thymus and salivary gland is suggested. It is indicated that EBV evokes polyclonal-B-cell-proliferative diseases in immunocompromised hosts, such as transplant patients, which results in monoclonal malignant lymphomas. The suppression of immune functions in these patients is thought to lead to incomplete elimination of the cells expressing EBV latent infection genes. To examine the etiological role of EBV in the development of malignancies following renal transplant in Japan, 42 malignancies in 1744 cases of renal transplant were studied for the presence and type of EBV. The polymerase chain reaction revealed that 5 malignancies were positive for EBV, all type A: 2 of 2 cases of non-Hodgkin's lymphoma (NHL), 2 of 8 cases of gastric adenocarcinoma of the common type, and 1 of 2 cases of gastric plasmacytoma. In situ hybridization revealed positive signals in the nucleus of tumor cells in 2 cases of NHL and 1 of plasmacytoma. Positive signals were found in the small lymphoid cells but not in the tumor cells in 2 cases of gastric carcinoma. On the basis of these findings, a role for EBV in the development of malignancies in renal transplant patients is unlikely except for lymphoid neoplasias.

Malignant lymphoma of the breast. Immunologic type and association with lymphocytic mastopathy.

Clinical and pathologic findings in 19 cases of primary non-Hodgkin's lymphoma of the breast collected from several hospitals in Japan were reviewed. All patients were women (median age, 45 years) and they usually had breast masses that had recently become enlarged. The sites of the lesions were the right breast in eight cases, the left breast in eight, and both breasts in one. The locations of two masses were unknown. Lymphoma recurred in the opposite breast in three cases 14, 23, and 23 months after surgery. Histologically, diffuse large cell lymphoma was the most common form of disease (63%). One lesion was a follicular lymphoma. The so-called lymphoepithelial lesion, a characteristic finding for mucosa-associated lymphoid tissue type lymphomas, was observed in eight cases (42%). Immunohistochemical analysis revealed that all but two tumors were of B-cell type; such findings confirmed morphologically based conclusions. Histologic and immunohistochemical evidence of lymphocytic mastopathy, a recently described autoimmune disease of the breast, was found in most of the cases. Formation of lymphoid follicles in or around the tumors was found in five cases (26%). Based on these findings, it is suggested that most mammary lymphomas are B-cell tumors and they may be associated with coexisting or antecedent lymphocytic mastopathy.

Biopsy findings in malignant histiocytosis presenting as lethal midline granuloma.

Nasal biopsy findings in malignant histiocytosis presenting clinically as lethal midline granuloma are characterised by necrosis and infiltration of atypical histiocytic cells with a diffuse positive reaction for non-specific esterase. This cellular character was common to midline malignant reticulosis, and midline malignant reticulosis and malignant histiocytosis are thought to be the same disease. Patterns of histiocytic infiltration in the nasal lesions of 19 cases are reported in this paper. Polymorphic and monomorphic patterns were observed in 11 and four cases respectively, on the initial biopsy, but subsequently the infiltrates frequently became monomorphic on serial biopsy. The reverse was not observed. Surface marker and cytochemical studies showed the true histiocytic nature of the proliferating cells, and necropsy findings justified the diagnosis of malignant histiocytosis.