Nobuhide Masawa

Clinical Implications of Idiopathic Multicentric Castleman Disease Among Japanese: A Report of 28 Cases

To clarify the clinicopathologic findings of idiopathic multicentric Castleman disease among Japanese, 28 cases were studied. Two variants were delineated by the clinicopathologic findings (1) idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (n = 18) and (2) nonidiopathic plasmacytic lymphadenopathy type (n= 10). Clinicopathologically, idiopathic plasmacytic lymphadenopathy was defined by the prominent polyclonal hyperimmunoglobulinemia, normal germinal centers, and sheet-like infiltration of plasma cells in the interfollicular area of the lymph node. Histologically, the nonidiopathic plasmacytic lymphadenopathy type was characterized by hyaline-vascular germinal centers of the lymph node lesion. In comparison with idiopathic plasmacytic lymphadenopathy, patients with nonidiopathic plasmacytic lymphadenopathy showed infrequent prominent polyclonal hyperimmunoglobulinemia and frequent association with autoimmune disease. However, there was no difference in the overall 5-year survival between the 2 subtypes. Compared with idiopathic multicentric Castleman disease in Western countries, the chronic course of the disease of idiopathic multicentric Castleman disease in Japan appears to be related to negativity for human herpesvirus 8 infection.

Primary salivary gland lymphoma among Japanese: A clinicopathological study of 30 cases

To clarify the clinicopathological findings of primary salivary gland lymphoma as defined by the World Health Organization (WHO) classification, 30 Japanese patients with this disease were studied. The male to female ratio was 1:1.7 and median patient age was 57 years. The parotid gland (n = 22) was involved most frequently, followed by the submandibular gland (n = 5) and minor salivary gland (n = 3). Twenty-four (80%) cases demonstrated Stage IE, whereas only six (20%) had Stage IIE-1. None of the 30 cases had “B” symptoms or a poor performance status. The 5-year overall survival of 31 cases was 96% and 5-year failure-free survival was 77%. Histologically, 15 cases were mucosa-associated lymphoid tissue (MALT) lymphoma, seven were follicular lymphoma (FL), and six were diffuse large B-cell lymphoma (DLBCL) + MALT lymphoma and only two were DLBCL without a MALT lymphoma component. MALT lymphoma is the most frequent type of primary salivary gland lymphoma. However, FL comprised 20% of primary salivary gland lymphoma. The majority of the primary salivary gland DLBCL appear to arise from MALT type lymphoma. When appropriate therapy for histologic subtype is used, outcome of the primary salivary gland B-cell lymphoma appears excellent whether histologically indolent or aggressive.

Comparison of 5-Fluorouracil-related Gene Expression Levels Between Adenocarcinomas and Squamous Cell Carcinomas of the Lung

BACKGROUNDnA recent meta-analysis study showed that post-operative adjuvant chemotherapy with UFT, an oral combination drug composed of tegafur [prodrug of 5-fluorouracil (5-FU)] and uracil [inhibitor of dihydropyrimidine dehydrogenase (DPD)] was associated with improved survival in patients with lung adenocarcinomas, but not in those with lung squamous cell carcinomas.nnnMETHODSnWe investigated the 5-FU-related gene expression levels of thymidylate synthase (TS), DPD, thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) in resected tumor specimens from 51 patients with adenocarcinomas and 47 with squamous cell carcinomas using quantitative reverse transcription-PCR, and compared those levels between the two histological types.nnnRESULTSnThe relative gene expression values of TS, TP and OPRT were significantly lower in adenocarcinomas compared with squamous cell carcinomas, 1.60 +/- 0.86 versus 4.33 +/- 3.40 (P < 0.001), 0.84 +/- 0.52 versus 2.27 +/- 1.16 (P = 0.006) and 9.59 +/- 6.30 versus 16.94 +/- 12.04 (P < 0.001), respectively. The relative gene expression value of DPD was significantly greater in adenocarcinomas than those in squamous cell carcinomas, 2.33 +/- 1.22 versus 1.50 +/- 1.20 (P = 0.01). Lower expressions of TS and TP were observed more in adenocarcinomas (89.8%) than in squamous cell carcinomas (48.9%) (P < 0.001).nnnCONCLUSIONnThese data may explain that post-operative adjuvant chemotherapy with UFT was associated with improved survival in stage I patients with adenocarcinoma, but less with squamous cell carcinoma.

Late-phase inflammatory response as a feature of in-stent restenosis after drug-eluting stent implantation.

ObjectivesThe aim of this study was to compare pathological features among in-stent restenosis lesions after drug-eluting stent (DES) placement, those after bare metal stent (BMS) placement, and de-novo atherosclerotic lesions. BackgroundRestenosis after stenting is an over-reaction of the wound-healing response after vascular injury, which is characterized by a sequence of inflammation, granulation, extracellular matrix remodeling, and smooth muscle cell proliferation and migration. Recent advances in DES technology could considerably succeed in inhibiting this sequence of events. Thus, we hypothesized that the mechanism of in-stent restenosis after DES stenting might be different from that after BMS stenting as well as atherosclerosis. MethodsTissues obtained by directional atherectomy (DES: seven specimens, BMS: 17 specimens, and de-novo: 15 specimens) were immunostained for T lymphocytes (CD45), macrophages (CD68), smooth muscle cells (&agr;-smooth muscle actin), endothelial cells (von Willebrand factor), and activated platelets (P-selectin). ResultsThe accumulation of T lymphocytes tended to increase and that of macrophages increased significantly in the DES lesions compared with BMS lesions. No significant differences were observed for the other parameters evaluated. ConclusionPathological features of restenotic tissues after DES implantation showed a stronger inflammatory response compared with those after BMS implantation. Thus, the mechanism of restenosis after DES implantation may be different from that observed after BMS implantation.

In Situ Follicular Lymphoma Associated With Progressive Transformation of Germinal Centers

The authors report here a case of in situ follicular lymphoma (FL) associated with progressive transformation of the germinal center (PTGC). A 39-year-old Japanese male developed a mass in the right cervical region. Biopsy of the enlarged lymph node led to a diagnosis of PTGC. Then, 5 years later, the lymphadenopathy recurred. The second biopsy specimens contained numerous germinal centers, including PTGC. Although most follicles were cytologically reactive, a few GCs appeared to be somewhat monotonous, composed predominantly of centrocytes and lacking mitotic figures and tangible body macrophages. Immunohistochemical studies demonstrated that these atypical GCs were CD10+, CD20+, and bcl-2+, with λ-light-chain restriction. A previous report emphasized the differential diagnostic problem between PTGC and the floral variant of FL. However, the present case indicated that in situ FL should be added to the list of differential diagnoses for PTGC.

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.

Follicular lymphoma with prominent sclerosis ("sclerosing variant of follicular lymphoma") exhibiting a mesenteric bulky mass resembling inflammatory pseudotumor. Report of three cases.

We present three cases of follicular lymphoma (FL) exhibiting prominent sclerosis (sclerosing variant of follicular lymphoma), resembling inflammatory pseudotumor (IPT) of the lymph node, arising from mesenteric lymph node. Clinically all three cases represented bulky masses of the mesenteric lymph node. Histologically, the lesions were characterized by neoplastic lymphoid follicles separated by stromal collagenization and sclerotic process, with cellular infiltrate extending into the adjacent adipose tissue. The lesions contained variable cellular spindle cell proliferation and inflammatory infiltrate including numerous reactive T cells and histiocytes. Small capillary proliferation with vascular change was also noted. Immunohistochemical study demonstrated the myofibroblastic nature of the spindle cells. Moreover, neoplastic follicles were composed of intermediate to medium-sized lymphocytes, somewhat resembling reactive lymphoid aggregates. The overall histomorphological findings of the three lesions were similar to those of IPT of the lymph node. However, CD10, Bcl-2 and Bcl-6 immunostaining demonstrated the neoplastic nature of the lymphoid follicles and the lesions were diagnosed as FL grade 1. The present three cases indicate that the sclerosing variant of grade 1 FL should be added to the differential diagnosis from IPT of the lymph node.

Nodal marginal zone B-cell lymphoma associated with Sjögren's syndrome : A report of three cases

Department of Pathology and Clinical Laboratories, Gunma Cancer Center Hospital, Ohta, Japan, Department of Medicene and Clinical Science, Gunma University School of Medicine, Maebashi, Japan, Department of Hematology, National Nishigunma Hospital, Shibukawa, Japan, Department of Pathology and Clinical Laboratories, Ashikaga Red Cross Hospital, Ashikaga, Japan, and Department of Diagnostic and Anatomic Pathology, Dokkyo Medical University School of Medicine, Mibu, Japan

Pathological features of in-stent restenosis after sirolimus-eluting stent versus bare metal stent placement

A 70-year-old man developed diffuse restenosis in the right coronary artery, in which a bare metal stent (BMS) and two sirolimus-eluting stents (SES) were deployed sequentially. He underwent directional coronary atherectomy (DCA) for in-stent restenosis (ISR) lesions 13 months after both BMS and SES stenting. Further 4 months later, that is, 17 months after stent implantation, however, ISR recurred just at the SES site alone. Then we performed second DCA for the ISR lesion at SES site. The tissue materials obtained from debulking were compared histologically. In the first DCA specimen, accumulation of inflammatory cells such as T lymphocytes and macrophages was observed densely in ISR lesions at SES site but not in those at BMS site, and endothelial coverage was absent in ISR lesions at SES site but present in those at BMS site. In the second DCA specimen, ISR lesions at SES site showed less inflammatory cells, compared with first DCA specimen. ISR lesions after drug-eluting stenting showed persistent signs of delayed or incomplete wound healing and relapsed inflammation, compared with BMS. Thus, the mechanism of restenosis after drug-eluting stenting may be different from that after BMS placement.

Tonsillar lesions of infectious mononucleosis resembling MALT type lymphoma. A report of two cases.

Infectious mononucleosis (IM) is an acute lymphoproliferative disorder that typically occurs in young patients and is usually caused by Epstein–Barr virus. We report here, two cases of tonsillar lesion of IM resembling marginal zone B-cell lymphoma mucosa-associated lymphoid tissue (MALT) type. The patients consisted of an 18-year-old Japanese woman and a 36-year-old Japanese man. Both patients presented with tonsillar mass. Histologically, in one case, the tonsil showed diffuse proliferation of medium-sized lymphocytes. The medium-sized lymphocytes had round or slightly indented nuclei with a small solitary nucleoli and abundant clear cytoplasm and somewhat resembled monocytoid B-cells. In the remaining one case, the lymphoid follicles had hyperplastic germinal centers with ill-defined borders surrounded by a sheet-like proliferation of polymorphous infiltration showing a marginal zone distribution pattern. On high-power field, the interfollicular area was diffusely infiltrated by a polymorphous infiltrate of medium-sized lymphocytes with angulated nuclei somewhat resembling centrocyte-like cells, immunoblasts, plasma cells, plasmacytoid cells and histiocytes with or without epithelioid cell feature. However, there were no CD43+ B-cells in either lesion. Moreover, the polytypic nature of the B-cells was demonstrated by immunohistochemistry or polymerase chain reaction. Although MALT type lymphoma rarely affected young adults, notably, a number of cases have been reported in the tonsil. The present two cases indicated that acute IM should be added to the differential diagnosis for MALT type lymphoma in young adults.