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.

Epstein-Barr virus-related atypical lymphoproliferative disorders in Waldeyer's ring: a clinicopathological study of 9 cases.

BACKGROUND AND STUDY AIM: Because of the small biopsy specimens in the Waldeyer's ring (WR) the differential diagnosis between Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) and malignant lymphoma is occasionally difficult. We report here clinicopathological, immunohistochemical and genotypic findings of 9 cases of EBV-associated LPDs in WR. PATIENTS AND METHODS: Using formalin-fixed paraffin-embedded sections, histological analyses, immunohistochemistry, in situ hybridization and polymerase chain reaction were performed. RESULTS: Clinically, all 9 cases showed more than one atypical clinical finding of infectious mononucleosis including absence of systemic symptoms, absence of atypical lymphocytosis and age over 30 years. Histologically, 3 types were delineated: (1) Hodgkin lymphoma-like (n = 1), (2) T cell/histiocyte-rich large B cell lymphoma-like (n = 4), and (3) marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT)-like (n = 4). The in situ hybridization study demonstrated EBV-encoded small RNA (EBER)+ cells in all 9 lesions. The immunohistochemical and flow cytometry study demonstrated the reactive nature of the B cells in all 9 lesions. However, 3 of our 7 cases examined demonstrated immunoglobulin heavy chain gene rearrangement on PCR study. There was no development of B cell lymphoma in any of the 3 lesions demonstrating IgH rearrangement. CONCLUSION: EBV-associated LPDs of the WR showed marked histological diversity. Among these, a MALT-like pattern was frequently seen. Marginal zone B cell lymphoma frequently affects WR. We emphasized that EBV-associated LPD should be added to the differential diagnosis of primary tonsillar MALT-type lymphoma.

Reactive lymphoid hyperplasia with giant follicles associated with a posttherapeutic state of hematological malignancies. A report of eight cases.

AIMS AND BACKGROUND: To further clarify the clinicopathological, molecular genetic and karyotypic findings of reactive lymph node hyperplasia with giant follicles (RLHGF) associated with a posttherapeutic state of hematological malignancies, we studied eight such cases. METHODS: Using formalin-fixed, paraffin-embedded sections, histological, immunohistochemical, in situ hybridization (ISH), and polymerase chain reaction (PCR) were performed. RESULTS: Six patients had a history of malignant lymphoma (diffuse large B-cell lymphoma [DLBCL] = 4, marginal zone B-cell lymphoma = 2), and two had acute myeloid leukemia (AML). Six patients initially presented with lymphadenopathy of the head and neck area and the remaining one presented with swelling of the tonsil. All seven cases demonstrating analyzable metaphases showed a normal karyotype. Histologically, all eight lesions were characterized by numerous enlarged, bizarre-shaped coalescing lymphoid follicles with follicular lysis. Immunohistochemical and flow cytometry study demonstrated the reactive nature of the B cells in all eight lesions. However, three of our eight cases demonstrated immunoglobulin heavy-chain (IgH) gene rearrangement on PCR study. Different clonal bands were detected in the initial lymphomatous tissue and RLHGF in one of the studied cases. There was no development of B-cell lymphoma or recurrence of B-cell lymphoma in any of the three lesions demonstrating IgH rearrangement. There were no human herpes virus type-8+ or human immunodeficiency virus type-1+ cells in any of the eight lesions. ISH demonstrated Epstein-Barr virus (EBV)-encoded small RNA (EBER)+ cells in only two lesions. PCR analyses demonstrated that there was no Toxoplasma gondii DNA in any of the eight lesions. CONCLUSIONS: As suggested in RLHGF posttransplant, RLHGF arising after therapy for hematological malignancies is also a consequence of chronic stimulation in the setting of immune deregulation rather than various infectious agents. It is important for pathologists and clinicians to be aware of this type of lesion in diagnostic practice.

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.

HIV-unrelated benign lymphoepithelial cyst of the parotid glands containing lymphoepithelial lesion--like structures: a report of 3 cases.

Benign lymphoepithelial cyst (BLC) of the salivary gland is uncommon. Among report of these lesions, there were no previous cases of lymphoepithelial lesion (LeL) in human immunodeficiency virus type-1 (HIV-1) unrelated BLC. This study reports 3 cases of HIV-unrelated BLC containing LeL-like structures. Pathologically, 3 lesions were characterized by cuboidal epithelial-lined, cystic spaces, numerous lymphoid follicles, and dense lymphoplasmacytoid infiltrate. Moreover, small lymphocytes invaded the epithelial clusters forming LeL-like structures. Histological findings of 3 lesions resembled marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. However, staining with CD3, CD5, and CD20 demonstrated the mixed nature of small lymphocytes invading the epithelial clusters (LeLlike structures). Moreover, there were no CD43+ B-lymphocytes in any of the cases. The polytypic nature of B-lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. The 3 cases indicate that HIV-unrelated BLC should be added to the differential diagnosis of MALT-type lymphoma involving the parotid glands.

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.

Incidental Langerhans cell histiocytosis of the parotid gland resembling marginal zone B-cell lymphoma: a case report.

Langerhans cell histiocytosis (LCH) manifesting as a parotid gland mass is an extremely rare clinical presentation. We report a case of LCH involving the bilateral parotid glands in an 81-year-old Japanese female. Pathologically, the lesion was characterized by numerous lymphoid follicles, dense lymphoplasmacytoid infiltrate and cystic dilatation of the parotid gland duct in addition to nodular and diffuse proliferation of LCs. Moreover, both LCs and small T-lymphocytes invaded the ductal epithelium forming a lymphoepithelial lesion-like morphology. The present case indicates that LCHs should be added to the different diagnosis for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type involving the salivary glands.

Küttner's tumor of the submandibular glands: report of five cases with fine-needle aspiration cytology.

Küttner's tumor (KT) is a benign tumor-like lesion of the salivary gland that mimics neoplasm clinically because of presentation as a hard mass. Recently, the histomorphological and immunohistochemical findings of this lesion have been analyzed, and differential diagnostic problems relating to salivary gland lymphoma have been discussed. However, currently there is little information on the cytological findings of those lesions. We present cytological findings from five such cases using fine-needle aspiration cytology (FNAC). FNAC of this lesion may present a diagnostic challenge to the cytologist as lesions share some cytologic features with inflammatory process containing numerous lymphoid cells. Smears obtained from two cases contained moderate to large numbers of lymphoid cells without definite cytological atypia, scattered ductal structures, and acinar cell clusters. The remaining three cases showed low cellularity probably attributable to fibrosis that made it difficult to aspirate the cellular element. FNAC findings of scattered ductal structures surrounded by collagens and infiltrated by a mixed population of lymphoid cells, not specific for KT, are highly suggestive of the diagnosis with the appropriate clinical findings. However, a portion of cytological specimens of KT containing relatively large numbers of lymphoid cells should be differentiated from malignant lymphoma arising from the submandibular gland.

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.