Acute intrahepatic cholestasis accompanied with Chlamydophila pneumoniae infection.

We report a case of Chlamydophila (C.) pneumoniae infection presenting with fever and rapid intrahepatic cholestasis. A 63-year-old man had a week-long history of intermittent high fever and rapidly progressive jaundice with atypical erythema. The results of liver function tests were recorded. The results of all serological tests were negative; the IgM, IgG, and IgA titers for C. pneumoniae had increased, which indicates a C. pneumoniae infection. The patient's fever and liver dysfunction improved upon administration of minocycline. Light microscopic findings showed the presence of enlarged liver cells with clear cytoplasm, a few mitotic figures, multinucleated cells, and bile cholestasis. The electron microscopic appearance of liver biopsy showed that bile canaliculi exhibited intrahepatic forms of cholestasis. From the results of light and electron microscopy, we inferred atypical intrahepatic cholestasis, probably resulting from the C. pneumoniae infection.

Primary hepatic presentation of Hodgkin's lymphoma: A case report.

Hodgkin's lymphoma (HL) is in general a lymph node-based disease. Hepatic involvement usually occurs in the advanced disease. Primary and prominent manifestation of the disease in the liver is extremely rare. We report magnetic resonance imaging leading to diagnosis in a rare case of liver involvement as the first sign of HL.

Histological diversity of reactive and atypical proliferative lymph node lesions in systemic lupus erythematosus patients.

Localized or generalized lymphadenopathy, which may be associated with systemic symptoms such as fever, is frequently found in patients with systemic lupus erythematosus (SLE). Histologically, the lymph node lesion is characterized by varying degrees of coagulative necrosis with hematoxylin bodies or reactive follicular hyperplasia. The former histology is unique to SLE, but is rarely seen in biopsied specimens. In this review, we describe a histologic variation of SLE lymphadenopathy based on the findings of our own cases, and discuss several problems related to the differential diagnosis of various benign and malignant lymphoproliferative disorders (LPDs). Among 33 cases we encountered, 17 (51%) cases exhibited atypical LPDs: (i) reactive follicular hyperplasia with giant follicles (RFHGFs), 3 cases; (ii) histologic findings of Castleman's disease (CD), 5 cases ; (iii) atypical paracortical hyperplasia with lymphoid follicles (APHLFs), 7 cases; and (iv) atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP), 2 cases. This finding indicates that atypical LPDs frequently appear in SLE. Moreover, the majority of patients with atypical LPDs exhibited follicular hyperplasia (RFHGF, 3 cases; histologic findings of CD, 5 cases; and APHLF, 7 cases). Previously, follicular hyperplasia was usually considered a non-specific change and therefore has received little attention in the literature. However, the present review indicates that reactive follicular hyperplasia in lymph nodes from SLE occasionally poses serious problems in the differential diagnosis of various benign and malignant LPDs. The presence of numerous copies of Epstein-Barr virus was determined by in situ hybridization studies in only two (8%) of the 26 cases examined. As previously suggested, the absence of EBV, as determined by ISH studies, in the majority of LPDs associated with SLE indicates that EBV is not related to the lymphoproliferative process, and suggests that the underlying cause of the patient's lymphadenopathy may reside in the immune deficit of SLE in the majority of reactive and atypical LPDs associated with SLE.

Human herpesvirus 8-unrelated primary effusion lymphoma-like lymphoma following tyrosine kinase inhibitor treatment for chronic myelogenous leukemia.

A 69-year-old man was diagnosed with chronic myelogenous leukemia (CML) and treated with dasatinib. After two years on dasatinib, the patient achieved complete molecular response, but dasatinib treatment was discontinued due to exacerbation of pleural effusion. Nilotinib and imatinib were started but stopped due to an increase in pleural effusion. Thoracentesis was performed and he was diagnosed with human herpesvirus 8-unrelated primary effusion lymphoma (PEL)-like lymphoma. Complex chromosomal abnormality, including BCL6 rearrangement, was found on chromosome analysis. To the best of our knowledge, this is the first report of PEL-like lymphoma following tyrosine kinase inhibitor treatment for CML.

Histological variety of floral variant of follicular lymphoma.

To further clarify the histopathological findings of the floral variant of follicular lymphoma (FVFL), we studied 13 Japanese cases. Two histological subtypes of neoplastic follicles of FVFL have been described: (i) A macrogerminal center pattern where the mantle zone lymphocytes were invaginated into the neoplastic germinal center, often reminiscent of a floral design. (ii) A microgerminal center pattern where the massive invasion of mantle zone lymphocytes resulted in almost complete breakage of the neoplastic follicles. In the former pattern, the neoplastic germinal center usually contained large clusters of tumor cells, whereas in the latter, small clusters of up to 20 tumor cells or isolated tumor cells were observed in the neoplastic germinal centers. Moreover, occasional tumor cells showed a lymphocytic and/or histiocytic Reed-Sternberg cell (L&H cells)-like morphology. Both types of neoplastic follicles were observed to a varying degree in most cases. The macrogerminal center pattern was predominant in nine cases (70%), whilst the microgerminal center pattern was predominant in only four cases (30%). Three lesions (23%) had a marginal zone component. Immunohistochemistry showed that atypical follicular center cells, including L&H cells, were CD3-, CD5-, CD10+, CD20+, CD43-, bcl-2+, cyclinD1-. The overall histological findings of the macrogerminal center are similar to those of florid progressive transformation of germinal center (PTGC), whilst the microgerminal center pattern is similar to that of nodular lymphocyte-predominant Hodgkin lymphoma. Initially, the differential diagnosis between FVFL and florid PTGC was emphasized. However, the present study indicates that nodal marginal zone B-cell lymphoma possessing floral follicles and nodular lymphocyte-predominant Hodgkin lymphoma should be added to the differential diagnosis of FVFL. The germinal center B-cell nature of FVFL is most clearly recognizable by immunohistochemistry, though histological appearance alone may cause some diagnostic problems.

Atypical lymphoplasmacytic and immunoblastic proliferation from rheumatoid arthritis: a case report.

A case of atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) in the lymph nodes associated with well-documented rheumatoid arthritis (RA) is presented. A 68-year-old Japanese female with a 6-year history of RA presented with right neck lymphadenopathy of 3 months duration. A biopsy specimen showed paracortical hyperplasia and numerous lymphoid follicles. On high-power field, the paracortical area was diffusely infiltrated by a polymorphous population consisting of numerous mature plasma cells, plasmacytoid cells, immunoblasts, including Hodgkin-like cells, small- to medium-sized lymphocytes, and histiocytes. Immunohistochemical study demonstrated that immunoblasts usually were CD20+, and a portion of them was CD30+. The histomorphological findings of the present case are similar to those of methotrexate (MTX)-induced atypical lymphoproliferative disorders (LPDs) in some aspects. However, Epstein-Barr virus-encoded small RNA-positive cells were not identified by in situ hybridization. The polytypic nature of B lymphocytes also was demonstrated by immunohistochemistry and polymerase chain reaction. Moreover, there was no history of MTX therapy in the present case, indicating that MTX-induced, LPD-like ALPIB may occur even in the RA patients not treated with MTX therapy.

Florid monocytoid B-cell hyperplasia resembling nodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue type. A histological and immunohistochemical study of four cases.

A pale ring of medium-to-large cells surrounding the follicles, namely a marginal zone distribution pattern, is the key criterion for diagnosing nodal marginal zone B-cell lymphoma (NMZBL). The tumor cells of NMZBL occasionally exhibit the morphology of monocytoid B-cells (MBC). However, this condition can be difficult to distinguish from MBC hyperplasia in reactive conditions. We describe the histopathological and immunohistochemical findings of four cases exhibiting florid MBC hyperplasia and resembling NMZBLs. The patients consisted of three males and one female (age range 48-64 years) who had asymptomatic lymphadenopathy in the head and neck area. Histologically, a pale ring surrounding more than 75% of the lymphoid follicles characterizes the lesion. The lymphoid follicles usually had hyperplastic germinal centers, and progressive transformation of germinal center was noted in two cases. The pale ring was composed of medium-to-large cells with indented or round nuclei and relatively abundant pale clear cytoplasm. Numerous plasma cells were observed in one case. The overall histomorphological findings in these four cases were similar to those of NMZBLs. However, immunohistochemical investigations demonstrated that MBCs were CD43- and bcl-2-. Moreover, immunohistochemistry, polymerase chain reaction, and flow cytometry studies demonstrated the polytypic nature of B-lymphocytes. Recognition of this unusual MBC hyperplasia in reactive lymph node lesions is important to avoid confusion with NMZBLs.

Histological varieties of Epstein-Barr virus-related lymph node lesion resembling autoimmune disease-like clinicopathological findings in middle-aged and elderly patients: a study of six cases.

Six cases were studied to further clarify clinicopathological findings of Epstein-Barr virus (EBV)-related lymph node lesions showing autoimmune disease-like clinicopathological findings (EBVAID) in middle-aged and elderly patients. The patients, four males and two females, ranged in age from 53 to 74 years, with a median age of 62 years. Clinically, they were characterized by systemic lymphadenopathy, "B"symptoms, polyclonal hypergammaglobulinemia, elevated serum lactate dehydrogenase and a transient presence of various autoantibodies, as well as an infrequent presence of atypical lymphocytosis in peripheral blood. Two cases were associated with idiopathic thrombocytopenic purpura. The clinical course was self-limiting. Histologically, three patterns could be delineated: pattern A, follicular hyperplasia with pronounced arborizing vasculature in the expanded paracortex (n=3); pattern B, follicular hyperplasia with pronounced interfollicular B-immunoblastic/plasma cell proliferation (n=2); and pattern C, paracortical hyperplasia containing numerous large transformed lymphocytes (n=1). In situ hybridization demonstrated a varying number of EBV-infected lymphocytes in the germinal center and in the interfollicular area. Polymerase chain reaction analysis demonstrated that neither clonal rearrangement of T-cell receptor gamma-chain nor immunoglobulin heavy-chain rearrangement was detected in the three cases examined. Although EBVAID appears to be rare in middle-aged and older adults, EBVAID exhibits histological variations and should be added to the differential diagnosis of various atypical or malignant lymphoproliferative disorders, in particular autoimmune-disease-associated lymphadenopathy and angioimmunoblastic T-cell lymphoma with a hyperplastic germinal center in middle-aged and elderly patients.

Atypical lymphoplasmacytic and immunoblastic proliferation from systemic lupus erythematosus. A case report.

A case of atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) in the lymph nodes associated with well-documented systemic lupus erythematosus (SLE) is presented. A 30-year-old Japanese female with an 18-year history of SLE presented with right neck lymphadenopathy of 3 months duration. A biopsy specimen showed a diffuse effaced lymph node architecture without follicles and minimal sinuses. At high power field, a polymorphous population of small- to medium-sized lymphocytes, plasma cells, plasmacytoid cells, as well as large, basophilic transformed lymphocytes and immunoblasts diffusely infiltrated the paracortical area. Interestingly, the immunohistochemical study demonstrated large, irregularly shaped accumulations of follicular dendritic cells (FDCs) surrounding the small vessels, which is an immunohistochemical finding characteristic of angioimmunoblastic T-cell lymphoma (AILT). However, the present lesion showed the following differences to AILT: (a) absence of CD3+, CD4+ and CD10+ clear cells, which are tumor cells of AILT; (b) absence of pronounced arborizing vascular proliferation; (c) on molecular analysis, the present case demonstrated a polyclonal pattern converse to the monoclonal T-cell receptor gamma chain gene rearrangement in most AILTs (d) absence of EBV infected lymphoid cells, which are frequently detected AILT. As previously suggested, the present case indicates that a clinical correlation as well as immunohistologic and genotypic studies may be necessary to discriminate between ALPIBPs and AILT.

Follicular colonization of nodal marginal-zone B-cell lymphoma resembling follicular lymphoma: report of 6 cases.

The formation of neoplastic B-cell follicles is accepted as a diagnostic criterion of follicular lymphoma. However, extranodal marginal-zone B-cell lymphomas (MZBLs) of mucosa-associated lymphoid tissue (MALT) type also sometimes contain numerous lymphoid follicles and may even have a predominantly follicular growth pattern. However, morphologic, immunohistochemical, and genotypic findings suggest that lymphoid follicles in extranodal MZBLs are neoplastic follicles formed as the result of colonization of previously reactive follicles by tumor cells (centrocyte-like cells). We present here 6 cases of nodal MZBL demonstrating a follicular growth pattern. Immunohistochemical study demonstrated that the tumor cells were CD10-, CD20+, CD79a+,CD138-, Bcl-2+, Bcl-6- and IRF4+. Residual nonneoplastic follicular center cells were CD10+, CD20+, CD79a+, Bcl-2-, and Bcl-6+. CD21/CD23 immunostain demonstrated a disrupted follicular dendritic cell pattern characteristic of follicular colonization in extranodal MZBL of MALT type. Taken in conjunction with the morphologic findings, nodal MZBL may also show a follicular growth pattern similar to extranodal MZBL of MALT type. The marginal-zone nature is most recognizable on immunohistochemistry, although the histologic appearance alone may cause some diagnostic problems. It is important for pathologists to consider this type of lesion in diagnostic practice.

Distribution of Epstein-Barr virus in systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis) with associated lymphadenopathy: a study of 49 cases.

Among systemic rheumatic diseases (SRDs), lymphadenopathy is frequently found in patients with rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) may occur in patients following methotrexate therapy for RA and dermatomyositis (DM). However, little is known about the distribution of EBV in reactive LPDs in patients with SRDs who had no history of methotrexate therapy. We analyzed 49 such patients (SLE=25, RA=23, DM=1) for the presence and distribution of EBV+ cells using Epstein-Barr virus (EBV)-encoded small RNA (EBER) specific in situ hybridization. A positive signal for EBERs was identified in 9 (SLE=5, RA=4) (18%) of 49 cases, and 3 main distribution patterns of EBER+cells could be delineated: pattern A, more than 500 EBER-positive cells were located in the germinal centers as well as interfollicular area (SLE=2); pattern B, EBER + cells were located in a few germinal centers (RA=2); and pattern C, up to 100 EBER+ cells were located in the interfollicular area (SLE=3, RA=2). Recent EBV infection may be a cause of lymph node lesion in only 2 cases of patients with pattern A. However, the pathognomonic significance of pattern B and pattern C EBER + cell distribution patterns still remains unclear. Our study indicates that the underlying immune deficits of patients with SRDs may also play an important role in the development of EBV-associated LPDs in SRDs, as previously suggested by several authors.

Clinical implication of florid reactive follicular hyperplasia in Japanese patients 60 years or older: a study of 46 cases.

Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in middle-aged or elderly patients requiring biopsy is a relatively uncommon phenomenon as compared with that in younger age groups. Between 1984 and January 2004, we encountered 46 patients, aged 60 years or older, in whom histology of biopsied lymph node specimens showed inappropriate FRFH for the patient's age. An apparent cause of lymphadenopathy was initially identified in 17 cases (37%): 11 with autoimmune disease and related disorders, 3 with cancer-reactive lymphadenopathy, 2 with Epstein-Barr virus-associated lymph node lesion exhibiting transient autoimmune-disease-like clinical findings, and 1 with atypical mycobacterial infection. Among 29 patients without specific etiology, 16 patients (55%) exhibited histologic findings of progressive transformed germinal center (PTGC). Only 1 of our patients developed malignant lymphoma during the follow-up period. The present study indicates that PTGC is included in the etiology of FRFH in elderly Japanese patients as well as imbalance of the immune system such as autoimmune-disease-associated lymphadenopathy and idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia. By in situ hybridization, Epstein-Barr virus genomes were demonstrated in only 6 (15%) of 39 cases examined.

Follicular hyperplasia presenting with a marginal zone pattern in a reactive lymph node lesion.

Histologically, the marginal zone pattern of the lymph node is characterized by lymphoid follicles with three distinct layers. The inner layer is composed of follicular center zones, the middle layer of darkly stained mantle zones, and the outer layer of marginal zones. However, the marginal zone pattern is rarely seen in reactive lymph nodes except for mesenteric lymph nodes. We describe the clinicopathologic, immunohistochemical and genotypic findings of six cases of reactive follicular hyperplasia exhibiting the marginal zone pattern. The patients comprised three males and three females (age range 24 to 63 years; medium 56 years). Follow-up data were obtained from five patients. None of them developed malignant lymphomas during the follow-up period of from 5 to 204 months (median 68 months). Histologically, the lesion was characterized by numerous lymphoid follicles and partial distortion of lymph node structure. Varying degrees of progressive transformation of the germinal center (PTGC) were noted in the four cases. The marginal zone pattern was observed in some or most of the lymphoid follicles including PTGC. The marginal zone B cells were small to medium-sized lymphocytes with round or slightly indented nuclei and a broad rim of pale cytoplasm. Some of them had a monocytoid appearance. They were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD10-, CD21-, CD23-, CD43-, CD45RO-, Bcl-6-, cyclin D1-, EMA- and p53-. A portion of them were Bcl-2 positive. Occasional large lymphoid cells with round or indented nuclei and moderate amounts of cytoplasm were observed in the marginal zone in four cases. These large lymphoid cells were usually CD20 positive, but Bcl-6 negative. A small number of them contained polytypic intracytoplasmic immunoglobulins. The polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Recognition of unusual marginal zone hyperplasia in reactive lymph node lesions is important to avoid confusion with nodal involvement in various low-grade B cell lymphomas presenting a marginal zone distribution pattern.

Primary marginal zone B-cell lymphoma of the lymph node resembling plasmacytoma arising from a plasma cell variant of Castleman's disease. A clinicopathological and immunohistochemical study of seven patients.

Nodal marginal zone B-cell lymphomas (NMZBL) occasionally represent prominent plasma cell differentiation. Recently, we presented a patient with NMZBL who exhibited histological features that resembled plasmacytoma arising from a localized plasma cell variant of Castleman's disease. To further clarify the clinicopathological, immunohistochemical, and genotypical findings, we studied seven such patients. Clinically, these patients were characterized by localized disease and an indolent clinical course with a slowly growing bulky mass in the affected lymph node. Only one patient exhibited paraproteinemia. Histologically, the lesions were characterized by numerous evenly distributed germinal centers in extensive sheets of plasma cells. Various numbers of centrocyte-like (CCL) cells arranged in a marginal zone distribution pattern occupied the peripheral region of the lymph node. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry showed that all of the lesions contained a monoclonal plasma cell population. In three tumors, a number of the CCL cells had a similar light chain restriction pattern to that observed in plasma cells. Two of the four patients evaluated exhibited clonal bands for the IgH gene by polymerase chain reaction assay. Moreover, the presence of surface IgM+, IgD- and CD27+ CCL- cells suggests that these tumors are derived from memory B-lymphocytes.

Apoptosis regulation differs between ulcerative colitis-associated and sporadic colonic tumors. Association with survivin and bcl-2.

To clarify kinetics in ulcerative colitis (UC)-associated lesions, cell proliferation, apoptosis, and expression of apoptosis-inhibitory proteins were studied. Ki-67 labeling and survivin and bcl-2 expression were examined immunohistochemically in 22 low-grade dysplasias (LGDs), 25 high-grade dysplasias (HGDs), and 13 adenocarcinomas associated with UC, and for comparison in 21 sporadic adenomas with LGD, 22 sporadic adenomas with HGD, and 21 invasive adenocarcinomas. Apoptosis was studied with nick-end labeling and immunohistochemical analysis of single-stranded DNA. In UC-associated LGDs, Ki-67--positive cells were more frequent in the lower than the upper half of the crypt, related to bcl-2 expression, while in sporadic adenomas such cells were more common in the upper half. No difference in apoptosis was found between UC-associated LGDs and sporadic adenomas with LGD or between UC-associated HGDs and sporadic adenomas with HGD. However, UC-associated carcinomas exhibited a lower apoptotic count than their sporadic invasive counterparts. This seemed related to higher survivin expression without a significant difference between the 2 types of invasive lesions regarding bcl-2 levels. Apoptosis is less frequent in UC-associated than in sporadic invasive colon carcinomas, this being linked to elevated survivin expression. The control of apoptosis may be different in the 2 types of tumorigenesis.

Progressive transformation of germinal centers: a clinicopathological study of 42 Japanese patients.

To clarify the clinicopathological features of progressive transformation of germinal center (PTGC) unrelated to nodular lymphocyte predominant Hodgkin's lymphoma in Japanese patients, we reviewed 42 cases and compared the results with those of the United States and Germany. Our results were similar to theirs, with male predominance (M/F ratio, 3:1) and the presentation of a solitary asymptomatic enlarged lymph node in the head and neck area as the common features. However, in Japan, PTGC occurs more frequently in elderly patients. In this study, 12 (29%) of the patients with PTGC were aged 60 years or more. Thirteen patients (31%) with lymphadenopathy in the neck and head area had developed localized chronic inflammation (chronic sialoadenitis=4, chronic tonsillitis=3, infectious epidermal cyst=2) or an autoimmune disorder (hyperthyroidism=2 and bronchial asthma=2). None of the patients developed a malignant lymphoma during the follow-up period of 5 to 238 months (median 27 months). Histologically, in a single longitudinal section of the lymph node, the PTGC occupied up to 5% of the total follicles in 22 patients, 5-10% in 10, 10-20% in 7, and more than 20% in 3. In 5 (12%) patients, an association with prominent marginal zone hyperplasia was also noted. This study also indicates that nodal involvement by various low-grade B-cell lymphomas exhibiting marginal zone distribution patterns should be considered as a differential diagnosis of PTGC. Moreover, in Japan, PTGC is thought to be involved in the etiology of florid reactive follicular hyperplasia in elderly patients.

IgG4-related disorder of the retroperitoneum resembling Castleman's disease plasma cell type: a report of 2 cases.

This study reports 2 cases of IgG4-related disorder of the retroperitoneum resembling plasma cell type of Castleman's disease. A single lesion was located in the renal hilum and ureter, respectively, in these 2 cases. Histologically, both lesions were characterized by reactive follicular hyperplasia with active germinal centers and a sheet of polyclonal mature plasma cells in the interfollicular area. The prominent sclerosis and/or fibrosis, which were characteristic histological findings of IgG4-related disorders, were absent. However, immunohistochemical study demonstrated numerous IgG4+ plasma cells accounting for more than 50% of IgG+ cells. The phlebitis that occurs with early lesions of obliterative phlebitis is one of the characteristic histological findings of IgG4-related disorders and was noted in one case. Serum IgG4 concentration was increased in one case. The serum interleukin-6 level was within the normal range in one case that was examined. From a therapeutic perspective, it is important to discriminate IgG4-related disorder from plasma cell type of Castleman's disease.

A case of drug-induced hepatic injury associated with sitagliptin.

A 58-year-old man with a 10-year history of type II diabetes mellitus presented with progressive jaundice that began three days before admission. Thorough history-taking revealed that the patient had started on a new medication, sitagliptin, one month previously for the treatment of diabetes mellitus. Laboratory investigations showed severe liver dysfunction. Ultrasonography detected no extrahepatic biliary duct dilatation or gallstones. Abdominal computed tomography excluded pancreatic and hepatic focal lesions. Liver function improved upon discontinuation of sitagliptin. Drugs are an important, often unrecognized, cause of acute liver injury. This report presents a rare case in which sitagliptin was responsible for acute hepatic damage. As demonstrated, a thorough drug history is helpful in any case of unexplained liver injury.

A case of cholestatic hepatitis associated with histologic features of acute cholangitis.

This report describes a case showing histologic features of acute cholangitis with an over-the-counter drug. A 48-year-old woman was diagnosed with general malaise and progressive jaundice. A thorough review of her medical history revealed that the patient had taken an over-the-counter drug, Pabron Gold(®), which she had used previously, that may have caused liver injury. Laboratory investigations revealed jaundice and liver dysfunction. Endoscopic retrograde cholangiography detected no extrahepatic biliary duct dilatation or stones. Liver biopsy indicated acute cholangitis involving neutrophils and eosinophils. Electron microscopy revealed fragmented nuclei, indicating that the degenerative bile duct-related epithelial cells were in an apoptotic process.

Association of an overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis with cytomegalovirus infection.

A 63-year-old woman, who presented with severe jaundice and elevated serum conjugated bilirubin level, denied alcohol and drug use and showed no evidence of viral hepatitis. Based on clinical and laboratory features, she was diagnosed with autoimmune hepatitis with primary biliary cirrhosis. Hematological and immunochemical assays, radiographic imaging, clinical examination, and liver biopsy were conducted. Laboratory results were the following: negative for fluorescence antinuclear antibody, negative for antismooth muscle antibodies but positive for antinuclear antibody (enzyme-linked immunosorbent assay) and antimitochondrial M2 antibody, high titers of serum globulin, and positive for cytomegalovirus IgM. Liver biopsy showed submassive lobular necrosis, inflammation with broad areas of parenchymal collapse, and chronic nonsuppurative destructive cholangitis. The patient responded well to corticosteroid therapy. This case might illustrate an association between cytomegalovirus infection and the occurrence of autoimmune hepatitis.