Atypical lymphoplasmacytic and immunoblastic proliferation of autoimmune disease : clinicopathologic and immunohistochemical study of 9 cases.

Atypical lymphoplasmacytic immunoblastic proliferation (ALPIB) is a rare lymphoproliferative disorder (LPD) associated with autoimmune disease (AID). To further clarify the clinicopathologic, immunohistological, and genotypic findings of ALPIB in lymph nodes associated with well-documented AIDs, 9 cases are presented. These 9 patients consisted of 4 patients with systemic lupus erythematosus, 3 patients with rheumatoid arthritis, and one case each with Sjögren's syndrome and dermatomyositis. All 9 patients were females aged from 25 to 71 years with a median age of 49 years. Four cases presented with lymphadenopathy as the initial manifestation. In 4 patients, immunosuppressive drugs were administered before the onset of lymph node lesion. However, none of the 9 patients received methotrexate therapy. The present 9 cases were characterized by : (i) prominent lymphoplasmacytic and B-immunoblastic infiltration ; (ii) absence of pronounced arborizing vascular proliferation ; (iii) absence of CD10(+) "clear cells" ; (iv) presence of hyperplastic germinal center in 7 cases ; (v) immunohistochemistry, flow cytometry, and polymerase chain reaction demonstrated a reactive nature of the T- and B-lymphocytes ; and (vi) on in situ hybridization, there were no Epstein-Barr virus -infected lymphoid cells in any of the 9 cases. Overall 5-year survival of our patients was 83%. The combination of clinical, immunophenotypic, and genotypic findings indicated that the present 9 cases can be regarded as having an essentially benign reactive process. Finally, we emphasized that ALPIB should be added to the differential diagnostic problems of atypical LPDs, particularly lymph node lesions of IgG4-related diseases.

Infectious mononucleosis lymphoadenitis showing histologic findings indistinguishable from toxoplasma lymphadenitis. A report of three cases.

Lymph node lesions in infectious mononucleosis (IM) show a marked histologic diversity. We report here three cases of IM lymphadenitis with histologic findings indistinguishable from those of toxoplasmic lymphadenitis. The histologic findings of the three cases presented here showed a histologic triad of toxoplasmic lymphadenitis, including (i) numerous lymphoid follicles with hyperplastic germinal centers; (ii) small clusters or single epithelioid histiocytes; and (iii) multiple foci of monocytoid B-cells. Moreover, all three lesions contained isolated or small clusters of epithelioid histiocytes within the hyperplastic germinal centers and the periphery of lymphoid follicles, which are the most specific histologic findings of toxoplasmic lymphadenitis. However, serologic findings confirmed EBV infection in all three cases. On in situ hybridization, numerous Epstein-Barr virus (EBV)-encoded small RNA (EBER)-positive cells were demonstrated in the germinal center, as well as in interfollicular areas in all three cases. Toxoplasmosis gondii infection was excluded in at least one case, based on serologic findings. Polymerase chain reaction analysis also demonstrated that there was no T. gondii DNA in the remaining two cases. Two of our three cases showed atypical clinical presentations, including an absence of atypical lymphocytosis in peripheral blood in two cases, age more than 30 years, and an absence of systemic symptoms in one case. It appears that previous descriptions emphasize the differential diagnostic problems between IM lymphadenitis and malignant lymphomas. However, from a therapeutic perspective, it is important to discriminate IM lymphadenitis from toxoplasmic lymphadenitis particularly in patients showing atypical clinical features.

Progressive transformation of the germinal center of extranodal organs: a clinicopathological, immunohistochemical, and genotypic study of 14 cases.

Progressive transformation of germinal center (PTGC) usually affects the peripheral lymph nodes. Little is known about the extranodal PTGC. To clarify the clinicopathological and molecular findings of extranodal PTGC, we studied 14 such cases. Using formalin-fixed, paraffin-embedded sections, we carried out histological and immunohistochemical examinations, as well as in situ hybridization (ISH) and polymerase chain reaction (PCR). Eleven patients were female, and three were male. They were between 44 and 77 years old, with a mean age of 62 years. The large intestine (n=7) was the most frequently involved tissue, followed by skin (n=2) and subcutaneous soft tissue (n=2). Oral cavity, Waldeyer ring, and orbit were affected in one case each. Histologically, 13 cases contained both early stage PTGC and late stage PTGC. The remaining 14th case contained only late stage PTGC. Expansion of the marginal zone was identified in three cases. Immunohistochemical study demonstrated the reactive nature of the B-cells in all 14 lesions. However, PCR study revealed immunoglobulin heavy chain (IgH) gene rearrangement in one of our 14 cases. There was no development of B-cell lymphoma in one lesion with IgH rearrangement. ISH study demonstrated Epstein-Barr virus-encoded small RNA+ cells in three lesions. Compared with PTGC of the peripheral lymph node, PTGC of extranodal sites was characterized by a female predominance, an older age group, and the presence of numerous PTGC at the affected sites. However, the histological findings of extranodal PTG were similar to those of lymph node PTGC. The clinicopathological findings of the extranodal PTGCs appeared to be different from those of lymph node PTGC.

B-cell lymphoma associated with Sjögren's syndrome among Japanese patients: a clinicopathologic and immunohistochemical study of 15 cases.

To clarify the clinicopathological findings of B-cell lymphoma associated with Sjögren's syndrome (SJS) among Japanese Patients, 15 individuals with this disease were studied. The patients, 14 females and one male, ranged in age from 41 to 73 years with a median age of 56 years. These lymphomas arose not only in the salivary gland (n=4) but also in other mucosal extranodal sites (n=5). Histologically, six cases were marginal zone B-cell lymphoma (MZBL) of the mucosa-associated lymphoid tissue (MALT) type, three cases were diffuse large B-cell lymphoma (DLBCL) + MALT type lymphoma, two cases were nodal MZBL and one case each was small lymphocytic lymphoma, Burkitt's lymphoma, CD10(+) DLBCL and DLBCL + nodal MZBL. Using in situ hybridization, numerous Epstein-Barr virus(+) tumor cells were detected only in the case of Burkitt lymphoma. There were no human-herpes type 8(+) tumor cells in any of the 15 cases. There was no API2-MALT1 fusion transcript in any of the eight cases examined. B-cell lymphoma associated with SJS also frequently affected extranodal organs in patients from Japan as well as from patients in Western countries. The majority of B-cell lymphomas in patients with SJS also appear to be low-grade MZBLs or high-grade lymphomas probably derived from MZBL both in Western countries and in Japan.

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.

Histopathological variation of primary mucosa-associated lymphoid tissue lymphoma of the oral cavity.

Primary mucosa-associated lymphoid tissue (MALT) type lymphoma arising in the oral cavity is rare. We examined histopathologic, immunohistological and genotypic findings of seven cases of intraoral MALT lymphoma using formalin-fixed paraffin-embedded tissues. Histologically, two variants have been delineated. (i) In four cases of minor salivary gland type, the lymphoid follicles were surrounded by centrocyte-like (CCL) cells with occasional follicular colonization. The CCL cells invaded the residual salivary gland duct resulting in a lymphoepithelial lesion. CCL cells frequently showed plasmacytic differentiation. (ii) In three cases of follicular growth type, the lesion was characterized by follicular growth pattern resulting from prominent follicular colonization. CCL cells showed minimal plasma cell differentiation. There was no residual epithelial component detected even by cytokeratin immunostaining. There were no Epstein-Barr virus-encoded small RNA-positive cells detected by in situ hybridization. API2-MALT1 fusion transcript does not appear to be associated with either histological variant of primary intraoral MALT lymphoma.

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.