Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent γδ T-cell receptor expression.

Enteropathy-associated T-cell lymphoma (EATL), an uncommon lymphoma of intestinal intraepithelial T lymphocytes, occurs with a higher frequency in northern Europe due to association with celiac disease. Data on the occurrence of EATL in the Asian population, among whom celiac disease is very rare, are conflicting. This study aimed to characterize EATL encountered in the Chinese population in Hong Kong. Eighteen cases were identified, all fulfilling the criteria of type II rather than classical EATL. The patients, including 13 men and 5 women, had a median age of 62 years. Most presented with small bowel perforation, and there was no history of malabsorption. The clinical course was aggressive, with 14 of 16 patients dying of progressive disease or complications, usually within 1 year. The histologic features were practically identical in all cases. The central zone of the tumor showed ulceration with or without perforation and was characterized by monotonous transmural infiltration of the bowel by small-sized or medium-sized lymphoma cells with few admixed inflammatory cells and no coagulative necrosis. The peripheral zone featured lateral spread of lymphoma cells in the mucosa, accompanied by variable involvement of the submucosa and muscularis. In all cases, there was an intraepithelial lymphocytosis zone contiguous or discontinuous with the peripheral zone, which was characterized by infiltration of the intestinal epithelium by nonatypical small lymphocytes, and not accompanied by other histologic changes of enteropathy. The most common phenotype of the lymphoma cells was CD3+, CD5-, CD4-, CD8+, CD56+, TIA1+, CD30-, and Epstein-Barr virus, and 2 cases showed aberrant expression of CD20. A remarkable finding was that 14 (78%) cases expressed γδ T-cell receptor, and only 6 (33%) expressed αß T-cell receptor (with 3 cases coexpressing both T-cell receptors and 1 case expressing neither). The immunophenotype of the intraepithelial lymphocytes was either discordant (particularly with respect to CD8 and CD56 expressions) or concordant with the lymphoma cells of the corresponding cases. Thus, this study shows that EATL occurring in the Chinese population is exclusively of type II. In contrast to several studies, intraepithelial lymphocytosis can be consistently demonstrated and this component seems to represent a precursor lesion of EATL rather than a manifestation of celiac disease. In view of the differences in epidemiology and clinicopathologic features, we believe it is justified to separate out type II EATL from the EATL category as a distinct form of lymphoma, for which we propose the designation "monomorphic intestinal T-cell lymphoma."

Survey for the presence of BK, JC, KI, WU and Merkel cell polyomaviruses in human brain tissues.

BACKGROUND: Recently three previously unknown polyomaviruses (KI, WU and Merkel cell polyomaviruses) have been identified from human specimens. The spectrum of clinical manifestations and their tissue tropism are currently unknown. Since a member of this virus family, JC virus, is well-known for its capacity to establish latency in human brain tissue where reactivation in immunocompromised individuals can result in fatal progressive multifocal leukoencephalopathy, we sought to examine for the presence of all the five known human polyomaviruses in a series of human brain tissues. OBJECTIVES: To investigate the possibility of neuropersistence of the newly identified human polyomaviruses. STUDY DESIGN: Autopsy brain tissues were collected from 10 different brain regions of 30 individuals who died from diseases unrelated to viral infections. Nested PCR was used to assess the presence or absence of viral DNA. RESULTS: Ten samples collected from five individuals were found to harbour JCV DNA. In contrast, none of the 300 brain tissues examined showed positive results for BK, KI, WU or Merkel cell polyomavirus. CONCLUSION: The newly identified KI, WU and Merkel cell polyomaviruses either do not, or have a much lower neuropersistent potential compared to JCV.

Diffuse large B-cell lymphoma associated with chronic inflammation as an incidental finding and new clinical scenarios.

Diffuse large B-cell lymphoma that develops in the setting of long-standing chronic inflammation is typically associated with Epstein-Barr virus, and usually presents as tumor mass involving body cavities, as in pyothorax-associated lymphoma. It is listed as a distinct entity in the latest World Health Organization lymphoma classification. We report four cases that were incidentally discovered on histologic examination, one each in a splenic false cyst, a long-standing hydrocele, an atrial myxoma, and metallic-implant wear debris. Microscopic foci of atypical (neoplastic) large lymphoid cells were found within the contents of the cysts or curettage material, or within the stroma of the atrial myxoma. Despite the diverse clinical scenarios, all cases showed a homogeneous phenotype: positivity for B-lineage markers (CD20+, CD79a+, PAX5+), non-germinal center immunophenotype (CD10-, BCL6-/+, MUM-1+), and positivity for Epstein-Barr virus with type III latency (LMP1+, EBNA2+). The last feature supports the hypothesis that the lymphoma has arisen in a setting of 'local immunodeficiency' as a result of long-standing chronic inflammation in an enclosed space, a characteristic pathogenetic mechanism of diffuse large B-cell lymphoma associated with chronic inflammation. These cases therefore expand the spectrum of this entity to include new clinical scenarios for the development of this lymphoma type.

Diagnostic cytological features of polyacrylamide gel injection augmentation mammoplasty.

AIMS: To study the cytological features of breast lesions associated with hydrophilic polyacrylamide gel (PAAG) injection augmentation mammoplasty and to determine the specific diagnostic features. METHODS: Fine needle aspiration (FNA) cytology smears from 14 patients who presented with breast lump and a clinical history of PAAG injection were reviewed. The staining properties of the PAAG material in Papanicolaou (Pap), Haematoxylin and Eosin (H&E) and Diff-Quik stains, as well as the cellular background, were studied. Cell blocks were also studied with H&E, periodic acid-Schiff (PAS), periodic acid-Schiff with diastase digestion (PASD) and mucicarmine (MC) stains. RESULTS: PAAG was stained consistently pinkish with a homogenous smooth texture on H&E (100%), polychromasia on Pap (100%) and magenta violet with bubbly vacuoles on Diff-Quik (100%). Half (7) of the cases showed sharp borders. The presence of foreign body type giant cells with histiocytes (5 cases, 36%) and scanty clusters of benign ductal cells (4 cases, 29%) were seen in the background of a minority of the cases. PAAG was represented by blocks of homogenous grey-purplish acellular material with a sharp border on cell block sections, which were negative for PAS, PASD and MC. CONCLUSION: PAAG shows a consistent staining pattern in various common cytological staining preparations. Blocks of acellular gelatinous material, stained homogenous pinkish on H&E, polychromasia on Pap and magenta violet with bubbly vacuoles on Diff-Quik, are the reliable cytological features of PAAG.

Distribution of human papillomavirus types in cervical cancers in Hong Kong: current situation and changes over the last decades.

Human papillomavirus (HPV) type distribution among cervical cancers and its possible changes over time are key issues that determine the cost-effectiveness of HPV vaccines. Cervical cancers diagnosed during 3 periods (1997-2007, N = 280; 1984-1986, N = 74; 1972-1973, N = 81) in Hong Kong were examined for HPV type distribution using sensitive broad-catching methods. The results showed a variation in HPV distribution between histological groups. Among cervical squamous cell carcinoma (SCC) cases diagnosed over the past 10 years, HPV16 was most commonly found (61.2%), followed by HPV18 (17.7%), HPV52 (14.7%) and HPV58 (9.9%), whereas adeno/adenosquamous cell carcinoma was dominated by HPV18 (56.3%) and HPV16 (50.0%). The proportion of HPV16-positive SCC showed a significant linear trend of increase with time (45.2% for 1972-1973, 58.8% for 1984-1986, 61.2% for 1997-2007; p(Trend) = 0.023), whereas HPV52-positive SCC decreased with time (30.1% for 1972-1973; 29.4% for 1984-1986, 14.7% for 1997-2007; p(Trend) = 0.001). Vaccines comprising HPV16/18 cover 62.6% of SCC and 93.8% of adeno/adenosquamous carcinoma in Hong Kong, and inclusion of HPV52 and HPV58 can increase the coverage by 18.4% for SCC and 4.1% for adeno/adenosquamous cell carcinoma. HPV type distribution may change over time. Further investigations to reveal the determinants for such changes and continuous monitoring for possible type replacement as a result of widespread long-term use of HPV vaccines are warranted. Multiple infections are commonly revealed by sensitive broad-catching methods such as those used in this study. However, their implication on vaccine efficacy and cost-effective analyses should be taken cautiously.

IgG4-related sclerosing mastitis: description of a new member of the IgG4-related sclerosing diseases.

Immunoglobulin G (IgG)4-related sclerosing disease is a recently described syndrome characterized by mass-forming lesions in various organs due to dense lymphoplasmacytic infiltrates and stromal sclerosis, elevated serum IgG4 titer, increased tissue IgG4 plasma cells, and favorable clinical outcome. We describe 4 patients with IgG4-related sclerosing mastitis, which represents a new member of this family of diseases. All patients were female with a mean age of 47.5 years, presenting with painless masses in 1 or both breasts. One patient had concurrent IgG4-related lymphadenopathy, and another had eyelid swelling of undetermined cause. The serum IgG4 titer was elevated in 1 tested patient, and circulating autoantibodies were found in 3 tested patients. All patients were well with no recurrence after excision or biopsy of the mass. Histologically, the breast masses featured dense lymphoplasmacytic infiltrates, prominent stromal sclerosis and loss of breast lobules. Phlebitis was present in 1 case. IgG4 cells ranged from 272 to 495 per high-power field, constituting 49% to 85% of all IgG cells. IgG4 cells were scarce in 9 of 9 cases of lymphocytic mastitis and 6 of 7 cases of granulomatous mastitis studied as controls. In summary, IgG4-related sclerosing mastitis appears to be a distinctive form of mastitis, sometimes accompanied by other components of IgG4-related sclerosing disease, and shows a favorable clinical outcome.

Ocular adnexal lymphoma associated with IgG4+ chronic sclerosing dacryoadenitis: a previously undescribed complication of IgG4-related sclerosing disease.

IgG4-related sclerosing disease is a recently recognized inflammatory lesion frequently involving pancreas, submandibular gland, lacrimal gland, and lymph node. We report 3 cases of ocular adnexal lymphoma arising in IgG4-related chronic sclerosing dacryoadenitis, a phenomenon that has not been previously reported. The patients presented with bilateral or unilateral ocular adnexal mass usually present for many years. One patient also had asymptomatic diffuse lymphadenopathy. Two patients had biopsy-proven IgG4-related chronic sclerosing dacryoadenitis before the current presentation, and 1 had systemic involvement by IgG4-related sclerosing disease as evidenced by increased IgG4+ cells in a prior nasopharyngeal biopsy. Two cases showed features of extranodal marginal zone lymphoma of mucosa-associated lymphoid-tissue type (1 with large cell transformation) and 1 follicular lymphoma. Thus, the lymphoid hyperplasia of IgG4-related sclerosing disease can provide a substrate for the emergence of lymphoma. In addition, we report 3 cases of ocular adnexal extranodal marginal zone B-cell lymphoma that show sclerosing inflammation in the background and numerous IgG4+ monotypic plasma cells. In the absence of prior biopsies or information on serum IgG4 titer, it is unclear whether these cases represent lymphoma complicating IgG4-related sclerosing disease or de novo lymphoma. Nonetheless, these cases are distinctive in that the neoplastic cells express IgG4 (light chain restricted), whereas unselected cases of ocular adnexal lymphomas do not show IgG4 expression.

Metallic implant-associated lymphoma: a distinct subgroup of large B-cell lymphoma related to pyothorax-associated lymphoma?

Primary non-Hodgkin lymphoma arising at the site of metallic implant is very rare, and the possible carcinogenic effects of the metallic components and wear particles of the implant have not been answered despite many years of investigation. We report a case of large B-cell lymphoma occurring in a 78-year-old man who had a knee prosthesis implant for more than 30 years. The lymphoma was of microscopic size and found incidentally in the wear debris removed at surgical revision of the loosened prosthesis. The lymphoma expressed CD20, showed clonal rearrangements of immunoglobulin gene, and harbored Epstein-Barr virus (EBV). This case, together with previously reported cases, suggests that metallic implant-associated lymphoma is a distinctive subgroup of large B-cell lymphoma that shares many similarities with pyothorax-associated lymphoma and osteomyelitis-associated lymphoma, in that the lymphoma is an EBV-associated large B-cell lymphoma arising in a setting of chronic inflammation or irritation in a confined body space.