A possible new morphological variant of mantle cell lymphoma with plasma-cell type Castleman disease-like features.

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by overexpression of cyclin D1 resulting from t(11;14)(q13;q32) translocation. Herein, we report 3 cases of MCL with features of plasma cell-type Castleman disease (CD). The 3 patients were all men, ranging from 51 to 74 years in age, and they all presented with systemic lymphadenopathy with anemia, hypoalbuminemia, elevated serum levels of C-reactive protein, and polyclonal hypergammaglobulinemia. Lymph node biopsy specimens of the 3 cases showed histological features of plasma cell-type CD, including atrophic germinal centers and interfollicular plasmacytosis, with no light chain restriction. However, flow cytometric analysis demonstrated an abnormal B-cell population with CD5 expression, and further analysis using cyclin D1 immunostaining highlighted a neoplastic component that was restricted to the mantle zone. These neoplastic cells were immunohistochemically positive for CD20, CD5, and SOX11, and negative for CD3, CD10, and HHV8. The Ki67 index was low. All patients were finally diagnosed with MCL. This rare type of MCL can be misdiagnosed clinically and histologically as CD. Therefore, it is important to recognize this rare type of MCL, and careful examination is required using both histological and flow cytometric analyses.

Type AB thymoma is not a mixed tumor of type A and type B thymomas, but a distinct type of thymoma.

Type AB thymoma is generally regarded to be a mixture of type A and type B thymomas, but has not been studied extensively. In this study, we precisely investigated the characteristics of type AB thymoma immunohistochemically and compared it with other types of thymoma, including type A, metaplastic, and type B1 thymoma. In type A thymoma, the tumor cells were composed solely of pan-cytokeratin (CK-AE1/AE3)(+) claudin-1(+) vimentin(-) epithelial membrane antigen (EMA)(-) short spindle cells. Metaplastic thymoma exhibited biphasic architecture of epithelial islands of short spindle cells, which were phenotypically almost identical to the tumor cells in type A thymoma, and anastomosing bundles of CK-AE1/AE3(-) claudin-1(-) vimentin(+) EMA(+) fibroblast-like long spindle-shaped epithelial cells. Interestingly, we found that there were two distinctive subtypes of cell in type AB thymoma: the conventional subtype and the metaplastic subtype. The conventional subtype is characterized by type A-like components resembling type A thymoma. The metaplastic subtype is characterized by type A-like components extensively resembling the anastomosing bundles of fibroblast-like long spindle epithelial cells. Interestingly, the metaplastic subtype was a major subtype (14/19 cases), while the conventional subtype was a minor one (5/19 cases). In contrast to the rarity of metaplastic thymoma, the metaplastic subtype of type AB thymoma appears to be a major subtype of type AB thymoma.

Low-grade B-cell lymphoma presenting primarily in the bone marrow.

Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.

Diagnostic accuracy of endoscopic biopsies for the diagnosis of gastrointestinal follicular lymphoma: a clinicopathologic study of 48 patients.

The purpose of this study was to reveal the diagnostic accuracy of initial pathologic assessment of biopsied samples in patients with gastrointestinal follicular lymphoma lesions. A total of 48 patients with follicular lymphoma (Lugano system stage I: n = 30; II1: n = 4; II2: n = 4; IV: n = 10) with gastrointestinal involvement who underwent endoscopic biopsy were enrolled and retrospectively reviewed. Nine (18.8%) of the 48 patients were not appropriately diagnosed as having follicular lymphoma at the initial biopsy. The initial pathological diagnosis included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (n = 4), necrotic tissue (n = 2), duodenitis (n = 1), or suspected lymphoma of unspecified subtype (n = 2). The reasons for these inappropriate diagnoses were insufficient histopathologic analysis lacking CD10 and BCL2 staining (n = 7) and unsuitable biopsy samples taken from erosions or ulcers that contained scanty lymphoma cells or no lymphoid follicles (n = 2). In conclusion, incomplete histopathologic analysis and unsuitable biopsy samples are pitfalls in the diagnosis of gastrointestinal follicular lymphoma.

Synchronous adenocarcinoma and follicular lymphoma of the stomach.

A 73-year-old Japanese man with synchronous follicular lymphoma and adenocarcinoma of the stomach underwent curative surgical resection. The follicular lymphoma lesion was preoperatively diagnosed as extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) according to biopsy samples. However, postoperative pathological evaluations revealed components of CD10-positive and CD10-negative lymphoma cells within the lymphoma lesion. This case highlights the potential difficulty of diagnosing gastric follicular lymphoma. In such cases, conducting repeat pathological examinations of biopsy samples or resected specimens is required to obtain a correct diagnosis of follicular lymphoma.

Pathological findings of infraorbital nerve enlargement in IgG4-related ophthalmic disease.

PURPOSE: We report a case of bilateral infraorbital nerve enlargement (IONE) associated with immunoglobulin (Ig)G4-related ophthalmic disease and describe the associated histopathologic findings. CASE: An otherwise healthy 59-year-old man presented with bilateral exophthalmos and right visual disturbance. Orbital magnetic resonance imaging showed bilateral IONE and a soft tissue mass in the right orbit. Excisional biopsy in the left infraorbital canal was performed. Histopathologic assessment revealed IgG4-related disease involving the epineurium of the infraorbital nerve. The patient received systemic steroid therapy, to which he responded well. CONCLUSION: IONE in IgG4-related ophthalmic disease is due to IgG4-related disease involving the epineurium.

Primary follicular lymphoma of the duodenum with erosions as atypical macroscopic features.

A 52-year-old Japanese woman who was eventually diagnosed with primary follicular lymphoma of the duodenum showed atypical endoscopic features, namely, erosions with peripheral whitish edematous mucosa. Initial biopsy specimens taken from the erosions revealed insufficient numbers of lymphoma cells for histological diagnosis. Subsequent biopsy specimens from the peripheral mucosa containing the whitish enlarged villi showed infiltration of the lymphoma cells forming lymphoid follicles, which led us to the appropriate diagnosis. This case indicates that endoscopists should take biopsy samples from the peripheral mucosa with whitish enlarged villi rather than erosions in the rare instances that erosions appear as the main macroscopic feature of intestinal follicular lymphoma.

[Case of primary malignant lymphoma of the liver treated by R-CHOP therapy].

A 75-year-old man was admitted to our hospital because of right hypochondralgia. Computed tomography (CT) revealed a large tumor in the right lobe of the liver. Ultrasonography (US) showed vessels in the tumor. Needle biopsy specimens showed malignant lymphoma (Diffuse large B cell lymphoma). Ga scintigraphy and FDG-PET did not demonstrate other lesions and the definitive diagnosis was primary malignant lymphoma of the liver. CHOP with Rituximab therapy (R-CHOP therapy) was performed. After 8 courses of therapy the FDG-PET results were negative and we considered complete remission. We describe a case of primary malignant lymphoma of the liver treated successfully by R-CHOP therapy.

[Effectiveness of preoperative chemoradiotherapy for advanced rectal cancer].

To determine the pathologic effectiveness of preoperative chemoradiotherapy (CRT) in patients with advanced rectal carcinoma, we reviewed clinical records of 76 patients who received preoperative pelvic radiation +/- chemotherapy. Since 2 patients refused operation and 2 died before surgery, 72 patients underwent operation with a mean delay of 19.9 days after completion of irradiation. Pathologic tumor regression grade (Grade 0-3) was determined by the amount of viable tumor versus necrosis and fibrosis. Grade 0, 1 a, 1 b, 2, and 3 (pCR) were observed in 0%, 25.0%, 38.9%, 27.8% and 2.8% of patients, respectively. The pathologic response (PR) rate was 75.0% when PR was defined as greater than grade 1 b (tumor regression more than 1/3). Downstaging was observed in 35.8% of patients, in which 5-year overall survival was significantly better than in patients without downstaging (90.0% vs. 50.1%, p<0.05). No correlation could be observed between PR and downstaging. CRT is a useful tool with a high PR rate in patients with advanced rectal cancer. More accurate and careful clinical staging is important to select adequate candidates for CRT. Multi-institutional clinical trials as well as standardizing the surgical procedure including LN dissection are required to validate the advantages of CRT for Japanese patients.

Familial epidermoid cysts of the spleen: report of two cases.

The familial occurrence of epidermoid cysts of the spleen is rare, with only six cases having ever been reported, to our knowledge. We recently diagnosed epidermoid cysts of the spleen in a mother and son. First, a 15-year-old boy was admitted to our hospital for management of blunt abdominal trauma. Computed tomography (CT) showed a ruptured large splenic cyst with an intraabdominal hematoma. We performed a splenectomy, and histopathological examination confirmed the existence of an epidermoid cyst of the spleen. About 2 years and 6 months later, the family physician found that the patient's 41-year-old mother had a large splenic cyst, and she was referred to our hospital for further investigation. CT showed a 10 x 8 cm cyst occupying most of the spleen. The patient underwent splenectomy, and a pathological diagnosis of an epidermoid cyst of the spleen was confirmed. Although the etiology of epidermoid cysts of the spleen is unclear, this familial occurrence may support the hypothesis of congenital malformation as a result of genetic change.

Dendritic cells interacting mainly with B cells in the lymphoepithelial symbiosis of the human palatine tonsil.

The lymphoepithelial symbiosis (LES) of the human palatine tonsil is composed of spindle- or star-shaped epithelial cells forming a loose meshwork, containing numerous lymphocytes and dendritic cells (DCs). In the present study, we immunohistochemically characterized DCs in the LES (LES-DCs). LES-DCs were phenotypically immature DCs that were S100beta+, fascin-, HLA-DR+, CD1a-, CD80-, CD83-, CD86-, and CD123-. The most characteristic feature of LES-DCs was that they contacted many B cells, which were mostly IgM+ IgD+ resting naive B cells. Langerhans cells (LCs) located in the nonsymbiotic squamous epithelium were immature DCs that were S100beta+, fascin-, and CD1a+ and did not contact lymphocytes. In contrast to LES-DCs, interdigitating dendritic cells (IDCs) in the T zone were mature DCs that were HLA-DR+, CD1a-, fascin+, CD80+, CD83+, and CD86+ and contacted numerous CD4+ T cells. Two subsets of IDC, S100beta+ fascin+ IDC (IDC-1) and S100beta- fascin+ IDC (IDC-2), were identified, and the majority of IDCs are IDC-2. In contrast to IDCs, which were distributed in the T-cell area in groups, LES-DCs were distributed along the crypt as if forming a barrier. These findings suggest that LES-DCs are a novel type of DC playing an important role in the induction of humoral immune response against incoming air- or food-borne pathogenic antigens.

[Improved quality of life in a patient with carcinomatous meningitis from invasive lobular carcinoma treated with intrathecal MTX and Ara-C in combination with systemic docetaxel].

Carcinomatous meningitis from breast cancer is rare and has a poor prognosis with a life expectancy of approximately 80 days. We performed intrathecal MTX and Ara-C in combination with systemic docetaxel treatments in the patient, a 44-year-old woman with carcinomatous meningitis from invasive lobular carcinoma previously treated with anthracycline and paclitaxel. Although the patient died 128 days after the onset, intrathecal chemotherapy in combination with systemic docetaxel reduced the number of malignant cells and induced degeneration of the cells in CSF, resulting in improved quality of life.

Occurrence of bronchioloalveolar cell carcinoma in two brothers: comparison of clinical features and immunohistochemical findings.

It has been suggested that lung cancer sometimes aggregates in families. However, the familial occurrence of bronchioloalveolar carcinoma (BAC) is extremely rare. We present a family in which two brothers had BAC. The clinical features and immunohistochemical findings of BAC in the two brothers were compared. Immunohistochemical findings revealed that both cases of BAC had very similar immunopathological features in epithelial marker expression. A review of the literature revealed that this is the third case of BACs in a single family.

Nonspecific interstitial pneumonia/fibrosis completely recovered by adding cyclophosphamide to corticosteroids.

Nonspecific interstitial pneumonia/fibrosis (NSIP) was first described by Katzenstein and Fiorelli in 1994 (Am J Surg Pathol 18: 136-147). Many reports have described that corticosteroids are effective for NSIP. We describe a case of group II idiopathic NSIP in whom cyclophosphamide was administered since the initial response to corticosteroids had been insufficient. Lung biopsy was performed by video-assisted thoracoscopic surgery and NSIP was diagnosed pathologically, clinically and radiologically. Although the initial response to corticosteroids was insufficient, interstitial infiltrates on chest computed tomography improved dramatically after adding intravenous cyclophosphamide followed by oral cyclophosphamide. This case demonstrates that the addition of cyclophosphamide to corticosteroids might be a useful treatment for patients with NSIP.

Evaluation of the clonality of multilobar bronchioloalveolar carcinoma of the lung: case report.

A case of multilobar bronchioloalveolar carcinoma (BAC) is reported. To investigate the clonality of BAC, immunohistochemical staining as well as genetic analysis were performed. To investigate point mutations of the p53 gene, we used the polymerase chain reaction and fluorescence-based single strand conformation polymorphism analysis method. The BAC tissues of the right upper lobe, right lower lobe, and the other lobes were considered to be multiclonal. This case suggests that multilobar BAC might occur with multiclonality.