Tseng-tong Kuo

Primary cutaneous marginal zone B-cell lymphoma: A molecular and clinicopathologic study of 24 Asian cases

Cutaneous marginal zone B-cell lymphoma is a recently proposed entity and constitutes a cutaneous counterpart of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Borrelia burgdorferi infection has been suggested as a possible causative agent in European cutaneous cases of marginal zone B-cell lymphoma, whereas API2-MALT1 fusion and BCL10 mutation are highly associated with MALT lymphoma. Aberrant nuclear BCL10 expression may be closely correlated with API2-MALT1 fusion in gastric and pulmonary MALT lymphomas. We examined 24 Asian cases of cutaneous marginal zone B-cell lymphoma for B. burgdorferi involvement, API2-MALT1 fusion, BCL10 cellular expression, and BCL10 mutation. Neither Borrelia DNA nor API2-MALT1 fusion transcript was detected. Nuclear BCL10 expression was evident in tumor cells of 11 of 24 cases, although BCL10 mutation was found in one case only. Clinicopathologically, nuclear BCL10 was more frequently expressed in macroscopically nodular lesions than in plaques or papules (p = 0.0031). These data suggest that 1) B. burgdorferi infection may not play an important role in developing cutaneous marginal zone B-cell lymphoma in Asian cases, 2) neither API2-MALT1 fusion nor BCL10 mutation is closely associated with the pathogenesis, 3) aberrant nuclear BCL10 may frequently be expressed in the absence of these genetic abnormalities, and 4) nuclear BCL10 expression may be clinically important because it was observed in locally aggressive tumors.

Lupus lymphadenitis simulating Kikuchi's lymphadenitis in patients with systemic lupus erythematosus : A clinicopathological analysis of six cases and review of the literature

Kikuchis disease (KD) or Kikuchis lymphadenitis (KL) is a self‐limiting disease mostly affecting the cervical lymph nodes of young individuals. Whether the reported cases of KL associated with systemic lupus erythematosus (SLE) were genuine KL or lupus lymphadenitis (LL) simulating KL in SLE patients is not clear. We analyzed six cases of KD‐like lymphadenitis occurring in SLE patients and 12 reported cases to clarify the relationship between KL and SLE. We found that not all cases occurred simultaneously with SLE. Eight cases occured either before or after SLE. These cases might have true KL independent of SLE with the exception of two cases that occurred after SLE, but the patients still had lupus activity. The 10 cases that coexisted with SLE most likelty had LL rather than KL. This was supported by the immunohistochemical finding of sparse cytotoxic T cells in those lymph nodes in contrast to abundant cytotoxic T cells usually seen in a typical KL. We conclude that KL is not related to SLE, and KD‐like lymphadenitis coexisting with SLE should be regarded as LL. Pathologists should be aware of the possibility that LL can mimic KL in patients with SLE, especially necrotizing‐type KL.

Primary cutaneous marginal zone B-cell lymphoma: a molecular and clinicopathological study of cases from Asia, Germany, and the United States

Primary cutaneous marginal zone B-cell lymphoma is considered the cutaneous counterpart of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Although its molecular pathogenesis is currently unknown, an etiological link with Borrelia burgdorferi infection has been identified in European, but not in American or Asian cases. To better understand the pathogenesis and the geographical differences of cutaneous marginal zone B-cell lymphoma, 60 cases from the East Asia, Germany, and the United States at their initial presentation were subjected to the following analyses; (1) clinicopathological comparison between the geographical regions, (2) detection of B. burgdorferi DNA, (3) detection of the API2–MALT1 fusion transcript, a gene alteration specific to mucosa-associated lymphoid tissue lymphoma, and (4) inactivation of tumor suppressor genes (death-associated protein kinase (DAPK), p16INK4a, p14ARF, MGMT, TIMP3, CDH1, and RARB) by hypermethylation of the CpG islands. Cases from the three geographical regions showed similar clinicopathological features. However, moderate/marked tissue eosinophilia was found in 9/25 Asian cases, but only 1/23 German cases (P=0.011) and 0/12 American cases (P=0.015). All 60 cases were negative for either Borrelia DNA or API2–MALT1 fusion. Tumors from the three regions were highly methylated for DAPK (38–50% of the cases, mean 43%) and p16INK4a (42–70%, mean 49%), and the positivities were significantly higher than those of nonneoplastic skin (8%, P=0.0010 and 14%, P=0.0032, respectively). Methylation of these genes had no significant association with progressive features of the tumor. Primary cutaneous marginal zone B-cell lymphomas from the three geographical regions have common clinicopathological features, however, moderate/marked tissue eosinophilia is a feature found almost exclusively in Asian cases. Borrelia infection and API2–MALT1 fusion are not significant in this tumor. Methylation of DAPK and p16INK4a genes is a frequent event in this lymphoma at its initial presentation, but may not be associated with tumor progression.

Follicular dendritic cell tumor of the liver: a clinicopathologic and Epstein-Barr virus study of two cases.

Two cases of hepatic follicular dendritic cell (FDC) tumor are described. Both patients were female, aged 57 and 51 years. They presented with epigastralgia or abdominal fullness and weight loss. The first patient refused surgical resection. She developed progressive polyclonal gammopathy and then bilateral purpura over the legs. Skin biopsy revealed leukocytoclastic vasculitis with granular vascular deposits of IgA and C3. The second patient had marked peripheral blood and tissue eosinophilia. The histological diagnosis was confirmed by positive staining for CD21 and CD23. The stromal lymphocytes were predominantly composed of CD3(+) and CD8(+) cells. In situ hybridization for EBER showed a positive nuclear signal in tumor cells but not in inflammatory cells. Polymerase chain reaction amplification for Exon 3 of the latent membrane protein-1 (LMP-1) gene showed a characteristic 30-bp deletion between nucleotides 168282 and 168253, corresponding to the B95-8 sequence. The unique clinicopathological features of our cases have not been reported for FDC tumors before. The clinical significance of the 30-bp deletion in Exon 3 of the LMP-1 gene in FDC tumor of the liver warrants further investigation.

Intrahepatic Cholangiocarcinoma with Lymphoepithelioma-Like Component

We present two cases of intrahepatic cholangiocarcinoma with lymphoepithelioma-like component. The patients included one woman and one man, aged 67 and 41 years, respectively. They presented with right upper quadrant pain and epigastralgia. Histologically, both tumors showed two distinct histological patterns with dense lymphoplasma cell infiltration. The first pattern was a well to moderately differentiated adenocarcinoma; the second component showed a feature similar to lymphoepithelioma-like carcinoma. Granulomatous reaction was noted in one case. Immunohistochemical study revealed that both tumors were immunoreactive with AE1/AE3, cytokeratin 7, and cytokeratin 19 but negative for carcinoembryonic antigen and cytokeratin 20. The stromal lymphocytes were composed of predominantly CD3(+) T cells. In situ hybridization for Epstein-Barr virus (EBV)–encoded RNA (EBER) showed positive nuclear signal in tumor cells but not in inflammatory cells in one case. The presence or absence of EBV genome was confirmed by polymerase chain reaction of LMP-1 gene in both cases. The LMP-1 gene also had a 30-bp deletion in Exon 3 as compared with the products from B95–8 cells. We further sequenced the PCR product and confirmed a 30-bp deletion between Nucleotide (nt) 168,282 and nt 168,253 corresponding to the B95–8 sequence. The clinical significance of 30-bp deletion in Exon 3 of the LMP-1 gene in lymphoepithelioma-like carcinoma of the liver warrants further investigation.

Unusual subcutaneous splenosis occurring in a gunshot wound scar: Pathology and immunohistochemical identification

Splenosis usually occurs after traumatic rupture of the spleen with autotransplantation of splenic tissue to ectopic sites. Most commonly, it occurs as intraperitoneal nodules, which are found either incidentally or after symptomatic complications. Subcutaneous splenosis is a rare condition mostly observed in abdominal surgical scars. Reported herein is a case of subcutaneous splenosis developed in an exit gunshot wound scar on the left lower chest wall 9 years after splenectomy. The lesion presented as an asymptomatic subcutaneous nodule, which was excised under the impression of a skin tumor. Microscopically, there were multiple subcutaneous nodules resembling splenic tissue with red and white pulp. They were confirmed to be ectopic splenic tissue by immunohistochemical staining of the vascular lining cells (CD8+, CD31+, and CD34–). Only 11 cases of subcutaneous splenosis have been reported before. The present case was the third case occurring in an exit gunshot wound scar, and the diagnosis was confirmed by immunohistochemical study.

Significance of histological subtypes of Kikuchi`s disease: comparative immunohistochemical and apoptotic studies

Kikuchis disease (KD) is a self‐limiting lymphadenitis mostly affecting the cervical lymph nodes of young individuals. It has been classified into three histological subtypes and postulated to progress from the proliferative type (PT) to the necrotizing type (NT) and finally resolve into the xanthomatous type (XT). Since KD has been shown to be an apoptotic disease, the apoptotic activity was studied by the TUNEL method on 6, 12, and 6 cases of PT, NT, and XT, respectively, to see if the apoptotic activity could be shown to decrease in the order of the postulated sequence of evoluation. Significant statistical difference among the three subtypes was found (P = 0.050). Further analysis revealed that PT versus NT was significant (P = 0.010), but NT versus XT (P = 0.385) or PT versus XT (P = 0.310) was not. Analysis of three stages of NT was also significant (P = 0.019). Immunohistochemical study showed that abundant CD8+ T cells and cytotoxic protein positive cells were present in PT and NT, but were relatively low in XT. Our results showed progression of PT to NT, but not from NT to XT. Xanthomatous type was not the resolving stage of KD, but seemed to be a distinctive histological variant of KD caused by either different etiology or an unusual host reaction.

Lipoid proteinosis: report of a possible localized form on both hands and wrists

A 28‐year‐old woman was seen for pruritic lesions on both hands and wrists which had been present since the age of 10 years. Both palms showed symmetric, diffuse hyperkeratosis extending over both wrists and the dorsal aspects of both hands with well‐demarcated, erythematous, lichenified plaques ( Figs 1 and 2 ). The borders of the plaques were pigmented and studded with papules ( Fig. 2 ). The skin lesions were not related to sun exposure. No similar lesions were found elsewhere on the body. The hair, nails, and dental development were normal. A skin biopsy was taken for histopathologic and ultrastructural studies under the clinical impression of pityriasis rubra pilaris.

Cutaneous plasmacytosis: a clinicopathologic study of 12 cases in Taiwan revealing heterogeneous underlying causes

Cutaneous plasmacytosis is clinically characterized by multiple pigmented papules and plaques that occur mainly on the trunk and many plasma cells in the lesional skin. Most of the cases reported have occurred in Japan. Whether cutaneous plasmacytosis is a unique reactive disease or a neoplastic condition has not been established.