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[Correlation between DNA ploidy patterns and tumor progression, prognosis, and tumor infiltrating lymphocytes in human esophageal cancer].

Cytophotometric DNA analyses were performed on 35 primary esophageal cancer. Histograms of DNA measurement were classified into three patterns (diploid pattern, aneuploid pattern and mosaic pattern) and were compared with histological findings, prognosis, and degree of lymphocytes infiltration around the tumor. Survival rate was worse in patients with mosaic pattern than the others, and 4-year survival rates of each patterns were 66.7% (diploid), 53.6% (aneuploid) and 25.4% (mosaic). Diploid cell line was observed frequently in the superficial cancers, and as the cancers infiltrated more deeply, mosaic cell line increased. Mosaic cell line appeared more frequently in well differentiated squamous cell carcinomas. In patients with mosaic pattern, there was high frequency of lymphnode metastasis and vascular invasion, as compared with diploid pattern. The rate of vascular invasion tended to increase in the following order; diploid, aneuploid and mosaic types. Furthermore in the diploid tumors, the degree of lymphocyte infiltration around tumor tended to increase. These findings suggest that the change of DNA content may occur frequently during tumor progression and may be affected by tumor infiltrating lymphocytes. So the DNA ploid pattern will be also to be one of the conjecturable factors of the prognosis of esophageal cancer.

Adult↗

Early-appearing tumour-infiltrating natural killer cells play a crucial role in the generation of anti-tumour T lymphocytes.

Natural killer (NK) cells that infiltrated into the primary tumour site at an early stage of tumour development, were examined for their participation in the generation of anti-tumour cytotoxic T lymphocytes (CTL). NK cells, which were detected by anti-NK1.1 monoclonal antibody (mAb), increased in the peritoneal exudate cells (PEC) on days 3 and 7 after an intraperitoneal (i.p.) inoculation of syngeneic B16 melanoma cells. These tumour-infiltrating NK cells showed a high level of cytotoxic activity against NK-sensitive YAC-1 cells and an increased expression of interferon-gamma (IFN-gamma) mRNA and interleukin-2 (IL-2) mRNA. The in vivo depletion of NK cells with anti-NK1.1 mAb, prior to i.p. inoculation of B16 melanoma cells, resulted in an increased number of tumour cells in the PEC compared to NK cell non-depleted mice. Interestingly, the differences in tumour cell number between both groups were more prominent on days 7 and 14 than on day 3, which strongly suggested that early-infiltrating NK cells have a large influence on the subsequent anti-tumour response. The in vivo depletion of NK cells prior to immunization with melanoma cells abrogated the capacity of the spleen cells to generate CD8+ tumour-specific CTL after in vitro restimulation. This inability of generating anti-tumour CTL was partially restored by additional i.p. injections of recombinant IL-2 and/or IFN-gamma simultaneously with the immunization of melanoma cells. The in vitro depletion of NK cells prior to the in vitro restimulation with melanoma cells partially impaired the anti-tumour CTL generation from the spleen cells of the immunized mice. Lastly, the in vivo depletion of NK cells prior to immunization with melanoma cells abolished the protective immunity against melanoma cells at the rechallenge. Overall, these results indicate that early-appearing tumour-infiltrating NK cells not only participate in the anti-tumour early defence by themselves, but also play a crucial role in the generation of anti-tumour CTL.

Animals↗

Oligoclonality of tumor-infiltrating lymphocytes from human melanomas.

A PCR-based method that determines VDJ junction size patterns in 24 human TCR V beta subfamilies was used to analyze T cells infiltrating sequential malignant melanoma biopsies for the presence of clonal expansions. Infiltrating T cell populations were found to present clonal expansions over a more or less complex polyclonal background. Two clones from a single patient were sequenced and detected in three different tumor sites (skin biopsies), whereas only one of them was also present in peripheral blood. Biopsies from this patient did not show major repertoire changes during in vivo IL-2 treatment. In contrast, in biopsies from a second patient, the expression of all the detected V beta subfamilies was increased and a larger number of clones expanded, probably as a result of therapy. A similar evolution was found among infiltrating T cells cultured in vitro from a third patient for several weeks in the presence of IL-2, where the largely polyclonal repertoire of fresh T cells (from invaded lymph nodes) was dramatically reduced to mainly clonal expansions in all V beta subfamilies detected. The high resolution method used here enables a rapid, comprehensive, qualitative, and semiquantitative description of the T cell repertoire of heterogeneous cell populations. Its use in conjunction with a functional analysis of clones detected within these populations should provide a better understanding of the evolution of the T cell repertoire among tumor-infiltrating lymphocytes during the progression of the disease and as a response to immunotherapy.

Base Sequence↗

[Isolated leukemic infiltration of the iris].

A boy 3 1/2 years old with the diagnosis acute lymphoblastic leukemia, in stage of high malignity, came to the Eye clinic in Hradec Králové. The clinical and haematological findings showed the remission of the illness but a leukemic infiltration with hypopyon had arised. The diagnosis has been done selon the clinic image of the eye and selon the ultrasound examination. The histologic finding showed also an infiltration of chorioidea, iris and ciliary body, an infiltration in the nuchal region, in the spleen and in testicles. The isolated leukemic infiltration of the iris can be the first sign of a relapse and is an indication to begin a relevant therapy.

Child, Preschool↗

Analysis of T-cell receptor V region gene usage of cytotoxic T-lymphocytes and tumor-infiltrating lymphocytes derived from human autologous gastric signet ring cell carcinomas.

To determine the T-cell receptor (TCR) V alpha/V beta gene usage of the human autologous gastric tumor-specific cytotoxic T-lymphocytes (CTLs), we first established two pairs of tumor cell lines, HST2 and SSTW, from the malignant peritoneal effusions of signet ring cell carcinomas and their peripheral blood lymphocyte-derived tumor-specific CD8-positive CTL lines, TcHST2 and TcSSTW. TCR V alpha/V beta gene usage from these CTL was examined using the reversely transcribed-polymerase chain reaction method, demonstrating that the V alpha 7, V alpha 12, and V beta 20 transcripts were commonly detected. The fact that repeated antigenic stimulation by mixed lymphocyte-autologous tumor cell cultures brought about the specific cytolysis and the restricted TCR usage of TCR V alpha 7, V alpha 12, and V beta 20 strongly suggests that these TCR V region products participated in T-cell-cancer interaction. This restricted TCR V gene usage in the gastric signet ring cell carcinomas led us to examine further the frequency of TCR V alpha/V beta usage in 11 cases of in vivo tumor-infiltrating lymphocytes with this particular type of tumor. The data showed that V alpha 7, V alpha 12, V beta 6, and V beta 20 were also predominantly expressed among these tumor-infiltrating lymphocytes in vivo. However, it seemed that T-cells with these TCR V region products are not specific for the gastric signet ring cell carcinomas, since they also frequently infiltrate into noncancerous lesions, such as peptic ulcers. These data may suggest that T-cells with certain TCR V alpha/V beta products could preferentially infiltrate into the stomach tissue, while some of these T-cells may be cytotoxic to the neoplastic autologous tumor cells.

Adenocarcinoma, Mucinous↗

Characteristics of MHC antigen expression and tumor-infiltrating mononuclear cells in renal cell adenomas and carcinomas.

We compared the expression of major histocompatibility complex (MHC; HLA class I and II) antigens and the presence of tumor-infiltrating mononuclear cells presenting S100 protein (S100), CD68 antigen, or CD45RO antigen in formalin-fixed, paraffin-embedded tissue sections of 10 renal cell carcinomas and 9 renal cell adenomas using immunohistochemistry. The expression of beta 2-microglobulin (B2MG) as an HLA class I antigen in all 10 cases (100%) and that of HLA-DR/alpha as an HLA class II antigen in 7 of 10 cases (70%) of carcinoma was stronger than that in the adjacent proximal convoluted tubule, but was respectively not different to weaker in 8 of 9 cases and not different to markedly weaker in all cases of adenoma. Furthermore, there was comparatively dense infiltration by S100(+) antigen-presenting cells in the carcinomas, but almost none in the adenomas and generally dense infiltration by CD45RO(+) T cells and CD68(+) macrophages in the carcinomas, but little to none in the adenomas. We concluded that the generally enhanced expression of MHC antigens in carcinomas must be an immunophenotypic deviation from not only the adjacent proximal convoluted tubule but also adenomas, and that the predominant infiltration of antigen-presenting cells, T cells and macrophages in the carcinomas, but not in the adenomas, reflects the anti-cancer immune reaction.

Adenoma↗

gamma-Interferon production in peripheral blood mononuclear cells and tumor infiltrating lymphocytes from Kaposi's sarcoma patients: correlation with the presence of human herpesvirus-8 in peripheral blood mononuclear cells and lesional macrophages.

Evidence indicates that, at least in the early stage, Kaposi's sarcoma (KS) is a cytokine-mediated disease and that it is consistently associated with a novel herpesvirus termed human herpesvirus-8 (HHV-8). To gain insights into the mechanisms by which cytokines and HHV-8 may cooperate in disease pathogenesis, we examined the phenotype, the Th1 (gamma-interferon [gamma IFN]) and Th2 (interleukin-4 [IL-4] cytokine profile and the presence of HHV-8 in peripheral blood mononuclear cells (PBMC), tumor-infiltrating lymphocytes (TIL), and spindle cell cultures derived from skin lesions of patients affected by classical KS (C-KS) and acquired immunodeficiency syndrome (AIDS)-associated KS (AIDS-KS). TIL and spindle cell cultures were examined at day 0 or after culture in conditioned media from activated T cells (TCM) that contain the same cytokines increased in KS tissues. No differences were found in the immunophenotype of PBMC from C-KS patients versus controls, except for AIDS-KS patients who showed a T-CD8+ expansion. However, a preferential infiltration of T-CD8+ cells was found in all KS lesions examined, which was maintained after culture of TIL in TCM. gamma IFN production was found in both PBMC and cultures derived from all KS examined; some IL-4 positive supernatants were found only in three AIDS-KS cases. Uninvolved skin did not show appreciable lymphocyte infiltration or cytokine production. The culture conditions of the lesional skin allowed also the appearance of adherent, spindle-like cells bearing markers of tissue macrophages. Finally, most or all of the PBMC, lesions, and macrophagic cell cultures from the skin lesions were found to be positive for HHV-8 infection by nested polymerase chain reaction (PCR). These findings indicate that patients with KS express a Th1 phenotype with a prevalent gamma IFN production, likely accounted for by the local T-CD8+ infiltration. By analogy with other viral infections (i.e., Epstein-Barr virus), this suggests that in loco recruitment of lymphoid cells and the subsequent gamma IFN production may be in response to or elicited by HHV-8 that was found in both PBMC and macrophagic cell cultures from the lesions of the same patients.

Adult↗

[Localized pulmonary infiltration in chronic myelomonocytic leukemia].

A 38-year-old woman who had been treated for refractory anemia was admitted with severe pancytopenia, persistent fever and splenomegaly in May 1995. The bone marrow biopsy revealed hyperplastic marrow with marked fibrosis. Shortly after admission, cardiac tamponade developed. Though low-dose Ara-C therapy successfully controlled the tamponade, no hematological recovery was obtained. Then a chemotherapy consisted of Ara-C, acrarubicin and M-CSF was done and the neutropenia was improved. However, progressive leukocytosis with monocytosis and splenomegaly subsequently developed. Thus, the disease was considered to progress to CMML. Localized pulmonary infiltrates associated with a cavity, a pulmonary artery aneurysm and a recurrent high fever developed in October 1995. Though invasive pulmonary aspergillosis was suspected, blood and sputa culture, as well as serological tests were negative. In February 1996, massive hemoptysis occurred and the patient died due to respiratory failure after an emergency right lobectomy of the lung. Pathological examination of the operated lung disclosed that the localized pulmonary infiltrates consisted of monocytoid cells. Infiltration of the monocytoid cells in the tissue surrounding the pulmonary aneurysm was also observed. However, no pathologic organisms were detected at all. Thus, the leukemic cells were considered to have infiltrated locally into the lung.

Adult↗

Immunohistochemical analysis of the T-cell receptor beta-chain variable regions expressed by T lymphocytes infiltrating primary human melanoma.

The T-cell receptor beta-chain variable (TCRBV) region repertoire expressed by tumor-infiltrating lymphocytes was characterized by immunohistochemical analysis using a panel of 18 monoclonal antibodies on cryosectioned specimens of 14 primary vertical growth phase (VGP) melanomas with a T-cell infiltrate histopathologically defined as brisk or nonbrisk. T lymphocytes present in the VGP of all patients displayed a restricted T-cell receptor usage, with a pattern of reactivity similar in brisk versus nonbrisk infiltrates. No evidence of restriction was found in the extra-VGP lymphocytic infiltrates, when available, within the same specimen. Furthermore, the repertoire of TCRBV expressed in nodal metastases was similar to that of the corresponding primary melanomas in the two cases tested. The results obtained by this in situ analysis indicate that the TCRBV repertoire in VGP is determined by a preferential migration of T lymphocytes, possibly indicative of an immune response to melanoma-associated antigens.

Adult↗

CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer.

The pathophysiological significance of tumor infiltrating lymphocytes remains controversial. To clarify their role, we performed clinicopathological analysis of CD8+ T cells in 131 cases of human colorectal cancer. CD8+ T cells were classified into three groups by their localization: (a) those infiltrated within cancer cell nests; (b) those distributed in the cancer stroma; and (c) those present along the invasive margin (tumor-host interface). Of these, CD8+ T cells within cancer cell nests were most significantly associated with a better survival of patients by both mono- and multivariate analyses. The impact on survival was similar to that of Dukes' staging. Granzyme B+ cytoplasmic granules were detected in lymphocytes within cancer cell nests, confirming their activated, cytotoxic phenotype. CD8 and Ki-67 double immunohistochemistry confirmed higher proliferative activity of CD8+ T cells within cancer cell nests. Our data suggested that human colorectal cancer tissue was infiltrated by various numbers of T cells that had cytotoxic phenotype, contributing to a better survival of patients. This infiltration of colorectal cancer cell nests by CD8+ T cells could be a novel prognostic factor.

Analysis of Variance↗

Cutaneous leukocytoclastic vasculitis. Serial histopathologic evaluation demonstrates the dynamic nature of the infiltrate.

Data from experimentally induced cutaneous vasculitis have suggested that the inflammatory infiltrate is dynamic. In contrast, data from humans with cutaneous vasculitis have suggested that two distinct patterns of cellular infiltrate exist, a mononuclear-predominant and a neutrophilic-predominant type. There are little data regarding the temporal evolution of spontaneously occurring cutaneous vasculitis in humans. A patient with a cutaneous leukocytoclastic vasculitis manifest as palpable purpura had four lesions encircled on the day of presentation. Biopsies of these lesions were obtained sequentially at 0, 24, 48, and 120 hours. The histopathologic specimens were graded without knowledge of the timing of the biopsy. The character of the infiltrate progressively changed from a neutrophilic-predominant to a mononuclear-predominant infiltrate supporting the theory of a dynamic process in cutaneous vasculitis. The previous reports that suggest that there are two distinct inflammatory cell types may be the result of performing the biopsy at one point in time during this transitory process.

Aged↗

Histiocytoid Sweet syndrome: a dermal infiltration of immature neutrophilic granulocytes.

OBJECTIVE: To describe a series of 41 patients with fresh lesions of Sweet syndrome in which the histopathologic study demonstrated an inflammatory infiltrate mostly composed of histiocytoid mononuclear cells. DESIGN: Histopathologic, immunohistochemical, and cytogenetic studies of the inflammatory infiltrate in a case series of histiocytoid Sweet syndrome. SETTING: University departments of dermatology and a private laboratory of dermatopathology. METHODS: Conventional histopathologic study as well as immunohistochemical investigations were performed using the alkaline phosphatase antialkaline phosphatase technique with a large panel of antibodies. In some cases, fluorescent in situ hybridization studies were performed to investigate the presence of the bcr/abl gene fusion. RESULTS: Immunohistochemical studies demonstrated that most cells of the infiltrate showed immunoreactivity for CD15, CD43, CD45, CD68, MAC-386, HAM56, and lysozyme, which is consistent with a monocytic-histiocytic immunoprofile. However, intense myeloperoxidase reactivity was detected in most of the cells with histiocytic appearance, which raised the possibility of specific cutaneous involvement by myelogenous leukemia. Nevertheless, cytologic peripheral blood examinations, fluorescent in situ hybridization studies to investigate the bcr/abl gene fusion, and follow-up of the patients, taken all together, ruled out this possibility. CONCLUSIONS: This case series demonstrates that some fresh cutaneous lesions of Sweet syndrome are histopathologically characterized by an infiltrate mostly composed of cells that may be misinterpreted as histiocytes, when in fact they are immature myeloid cells. We named this histopathologic variant histiocytoid Sweet syndrome, which should not be mistaken with leukemia cutis or other inflammatory dermatoses that are histopathologically characterized by histiocytes interstitially arranged between collagen bundles of the dermis.

Acetaminophen↗

Nonsteroidal anti-inflammatory drug-associated pulmonary infiltrates with eosinophilia. Review of the literature and Food and Drug Administration Adverse Drug Reaction reports.

OBJECTIVE: The purpose of this study was to detail the clinical and pathologic presentation of pulmonary infiltrates with eosinophilia (PIE) associated with nonsteroidal anti-inflammatory drug use. METHODS: We reviewed case reports and Food and Drug Administration Adverse Drug Reaction Spontaneous Reporting Program reports. RESULTS: A case of pulmonary infiltrates with eosinophilia related to naproxen use was studied. Six similar cases from the medical literature and 22 reports from the Food and Drug Administration were reviewed. Four cases of PIE associated with ibuprofen, obtained from the Food and Drug Administration, and single literature reports of PIE associated with fenoprofen and sulindac detailed similar clinical presentations. The clinical presentation of PIE syndrome associated with nonsteroidal anti-inflammatory drugs included fever, cough, dyspnea, infiltrates on chest roentgenogram, and an absolute peripheral eosinophilia. Pathologic examination revealed poorly defined granulomas with infiltrating eosinophils. CONCLUSIONS: Naproxen and other nonsteroidal anti-inflammatory drugs can elicit the PIE syndrome. The prevalence of this side effect is likely underestimated, given the extensive use of these drugs and the relatively benign course of PIE syndrome.

Aged↗

Recurrent infiltrating lipoma of the head and neck. Case report and literature review.

Lipomatous tumors with intramuscular infiltration are uncommon in the head and neck. Oral lipomas have been recorded in the literature; however, infiltration and recurrence have rarely been documented. We describe a case of an oral lipoma that did not have microscopic characteristics of malignancy, lipoblastomatosis, or atypia, but which showed intramuscular invasion and recurred twice after surgery. Although certain characteristics distinguish our case from congenital lipomatosis, the clinical picture is quite similar. Lipomas with intramuscular invasion uniformly tend to recur when they are not widely resected, whether in the trunk and extremities or in the head and neck. These lesions can rapidly enlarge and infiltrate local tissues, and they require wide resection with an attempt at preservation of important structures. Preoperatively, computed tomographic analysis allows a lipoma to be diagnosed by its low attenuation, and a grossly infiltrating tumor can be distinguished from the ordinary well-encapsulated lesion.

Child, Preschool↗

Patterns of human tumor-infiltrating lymphocytes in 120 human cancers.

Tumor-infiltrating lymphocytes from 120 samples of human cancers, including melanoma, renal cell carcinoma, breast cancer, sarcoma, and colon cancer, were examined. The percentage of lymphocytes recovered from the cancer varied widely; that of renal cell carcinoma was higher than that of breast or colon cancer (65% vs 45%), which was higher than that of melanomas or sarcomas (30% to 35%). The types of lymphocytes before and after interleukin 2 activation showed specific patterns. CD4+ helper T cells predominated in all tumors except melanomas, which had more CD8+ cytotoxic T cells. CD16+ natural killer cells were recovered in renal cell carcinoma and sarcomas. Three different cytotoxic lymphocytes were identified among interleukin 2-activated tumor-infiltrating lymphocytes: (1) CD3+ CD16- cytotoxic T lymphocytes with cytotoxicity restricted to autologous tumor cells in melanomas, (2) CD3-CD16+ natural killer cells with vigorous major histocompatibility complex-nonrestricted cytotoxicity in renal cell carcinoma, and (3) CD3+ CD16- T cells with modest levels of major histocompatibility complex-nonstricted cytotoxicity in all cancers except melanomas. Thus, there was considerable diversity of tumor-infiltrating lymphocytes among these histologically distinct tumors with respect to magnitude of lymphocyte infiltration, phenotypic expression, and functional capacity.

Breast Neoplasms↗

Comparing preincisional with postincisional bupivacaine infiltration in the management of postoperative pain.

OBJECTIVE: To determine if preemptive local anesthesia yields better postoperative pain control than infiltration of local anesthetic at the time of wound closure. DESIGN: Prospective, randomized trial. SETTING: Private community teaching hospital. PATIENTS: Two-hundred consecutive patients undergoing elective laparotomy were enrolled in the study between September 1993 and April 1995. Eighty-eight patients were excluded from the study for violation of protocol, leaving a total of 112 patients to be evaluated. Patients were divided into 2 groups: preincisional (n = 52) and postincisional (n = 60). INTERVENTIONS: Patients in the preincisional group received 40 mL of 0.25% bupivacaine (Marcaine) 5 minutes before the incision; patients in the postincisional group received 40 mL of 0.25% bupivacaine immediately after approximation of the fascia and before closure of the skin. MAIN OUTCOME MEASURES: The control of the long-term (3-day) postoperative pain in relationship to timing of local anesthetic given. RESULTS: Study groups were comparable for age, weight, sex, operative time, and length of incision. No significant difference in the amount of morphine used or subjective evaluation of pain was noted between the preincisional and the postincisional groups. CONCLUSIONS: Based on the theory of "dorsal horn hypersensitivity," several clinical trials have shown significant improvement in pain control with preincisional infiltration of local anesthetic. Our results indicate that pain was no better controlled with preincisional infiltration than with postincisional infiltration of bupivacaine, raising the question of the benefit of preemptive anesthesia at the local level in long-term postoperative care.

Adult↗

Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast.

CONTEXT: Zafirlukast is a potent leukotriene antagonist that recently was approved for the treatment of asthma. As use of this drug increases, adverse events that occur at low frequency or in populations not studied in premarketing clinical trials may become evident. OBJECTIVE: To describe a clinical syndrome associated with zafirlukast therapy. DESIGN: Case series. PATIENTS: Eight adults (7 women and 1 man) with steroid-dependent asthma who received zafirlukast. MAIN OUTCOME MEASURES: Development of a clinical syndrome characterized by pulmonary infiltrates, cardiomyopathy, and eosinophilia following the withdrawal of corticosteroid treatment. RESULTS: The clinical syndrome developed while patients were receiving zafirlukast from 3 days to 4 months and from 3 days to 3 months after corticosteroid withdrawal. All 8 patients developed leukocytosis (range, 14.5-27.6 x 10(9)/L) with eosinophilia (range, 0.19-0.71). Six patients had fever (temperature >38.5 degrees C), 7 had muscle pain, 6 had sinusitis, and 6 had biopsy evidence of eosinophilic tissue infiltration. The clinical syndrome improved with discontinuation of zafirlukast treatment and reinitiation of corticosteroid treatment or addition of cyclophosphamide treatment. COMMENT: Development of pulmonary infiltrates, cardiomyopathy, and eosinophilia may have occurred independent of zafirlukast use or may have resulted from an allergic response to this medication. We suspect that these patients may have had a primary eosinophilic infiltrative disorder that had been clinically recognized as asthma, was quelled by steroid treatment, and was unmasked following corticosteroid withdrawal facilitated by zafirlukast.

Adult↗

Clonality of B-cells in portal lymphoid infiltrates of HCV-infected livers.

Evidence has been accumulating in favour of a role for hepatitis C virus (HCV) in the pathogenesis of human lymphoproliferative disorders. HCV infection has been documented in the majority of patients with essential mixed cryoglobulinaemia type II (MC-II); in patients with HCV infection, B-cell clonal expansion have been detected in peripheral blood and bone marrow, and a high prevalence of B-cell non-Hodgkin's lymphomas has been documented. Liver biopsies in chronic hepatitis C frequently show portal lymphoid infiltrates with features of B follicles, whose clonality has not yet been investigated. This study has analysed the B-cell clonality of portal lymphoid infiltrates from 16 patients with chronic HCV hepatitis. Portal tracts showing obvious lymphoid infiltrates were microdissected from the paraffin-embedded liver tissue sections and the clonality of lymphoid B-cells was tested using a polymerase chain reaction (PCR) approach designed to identify immunoglobulin heavy chain gene (IgH) rearrangements. A successful IgH-PCR analysis was achieved in 35 lymphoid infiltrates from 11 patients (seven with the four without MC-II) and yielded a single band in 21 cases, two bands in ten cases, and three bands in four cases. Comparison of the IgH-PCR amplification bands obtained from the different lymphoid aggregates of the same biopsy revealed that they differed in size. This finding indicates that each aggregate derives from the proliferation of one or a few founder B-cells, which are not related to each other. The results obtained in patients with and without MC-II were similar, suggesting that the presence of B-cell clonal proliferations in liver biopsies is independent of the occurrence of B-cells producing monoclonal IgMk cryoglobulins.

B-Lymphocytes↗