Kanita Kayasut

Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αβ, γδ, and αβ/γδ T-cell origin: a comprehensive clinicopathologic and phenotypic study.

Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of &agr;&bgr; or &ggr;&dgr; type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 &ggr;&dgr; enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) &bgr;,&ggr; and, in cases tested, &dgr; negative (presumptive NK origin); 5% were TCR &ggr;&dgr;+, 3% were TCR &agr;&bgr;+, 1% were TCR &agr;&bgr;/&ggr;&dgr;+, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV+ and TIA-1+; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16−. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2+ compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1+ compared with 20% of T-ENKTLs. Only &agr;&bgr; T-ENKTLs were CD5+. Intestinal ENKTLs were EBV+ and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with &ggr;&dgr; EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal &ggr;&dgr; EATL.

Clinical presentation, treatment, and prognosis of periocular and orbital amyloidosis in a university-based referral center

Objective The purpose was to present the demographic data, clinical presentation, and treatment options, and to evaluate prognosis, for periocular and orbital amyloidosis in patients at the Songklanagarind Hospital, Thailand. Method This was a retrospective study that reviewed the clinical records of six patients who were diagnosed with periocular and orbital amyloidosis between January 1, 2002 and December 31, 2011. Results The series included six patients (five female and one male). The mean age was 39.7 years (range 15–79 years). There were five cases of unilateral lesion and one case of bilateral lesion. The most common symptom was a mass lesion (83.3%), followed by irritation (66.7%), bloody tears (16.7%), epiphora (16.7%), eye pain (16.7%), and ptosis (16.7%). Five cases had periocular involvement and one case had orbital involvement. Five cases were investigated to rule out systemic amyloidosis, and no systemic involvement was found in these cases. The median duration of symptoms was 6 months, but the mean was 31 months. The main treatment option was surgical excision. The mean follow-up time was 41 months. There was disease progression in 20% of cases after definitive treatment. Conclusion Periocular and orbital amyloidosis presented with a variety of symptoms, depending on the location of the disease. A mass lesion was the most common symptom. The intent of the treatment modalities was to spare function.

Cushing's Syndrome in an Infant Secondary to Malignant Adrenocortical Tumors with Somatic Mutation of Beta-Catenin

A role of beta-catenin (CTNNB1) in the molecular pathogenesis of adrenocortical carcinoma (ACC) has been suspected in adult ACC and pediatric pigmented nodular adrenocortical disease, but it has never been reported in pediatric ACC. We present the case of a 4-month-old Thai infant who had Cushings syndrome secondary to bilateral adrenal tumors with hepatic metastasis. The child was successfully treated with a bilateral adrenalectomy and wedge resection of the liver nodule. Histopathology revealed bilateral adrenocortical tumors with different histologic grades; the right tumor had a higher score, according to modified Weiss criteria. On molecular study, a deletion mutation of beta-catenin involving codons 44 to 45 was detected in the right adrenal tumor. The same mutation was found in peripheral blood before treatment; this mutation disappeared after tumor removal. The left tumor harbored wild-type beta-catenin. Immunohistochemistry showed nuclear accumulation of beta-catenin on the right adrenal tumor and the metastatic nodule. In summary, we present evidence that supports the role of the Wnt-signaling pathway in the carcinogenesis of pediatric adrenocortical carcinoma.

No Prognostic Impact of p53 and P-Glycoprotein Expression in Patients with Diffuse Large B-Cell Lymphoma

The aim of this study was to determine the clinical significances of p53 and p-glycoprotein (P-gp) expression on outcome predictors for patients with DLBC. We assessed the immunohistochemical expression of p53 and P-gp using formalin-fixed, paraffin-embedded specimens in 108 patients diagnosed with de novo DLBC. A high expression of p53 was found in 53.7% of the patients. No expression of P-gp was demonstrated in any of the specimens. There were no significant differences in the complete remission (CR) rate (P = 0.79), overall survival (OS) (P = 0.73), or disease-free survival (DFS) (P = 31) between the p53-positive and p53-negative groups. The final model from multivariate analysis that revealed poor performance status was significantly associated with CR (P < 0.001) and OS (P < 0.001). Moreover, the advanced stage was a significant predictor of DFS (P = 0.03). This study demonstrated no impact of the expression of p53 on either response or survival rates.

Erythema multiforme-like cutaneous lesions in monomorphic epitheliotropic intestinal T-cell lymphoma: a rare case report

Monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL), also known as Type II enteropathy‐associated T‐cell lymphoma (EATL), is an aggressive peripheral T‐cell lymphoma. EATL generally presents in adults with gastrointestinal symptoms. Skin involvement is very rare, found only in approximately five percent of patients. The authors report a 67‐year‐old Asian male who presented with chronic diarrhea and developed erythema multiforme‐like cutaneous lesions. A skin biopsy revealed extensive pagetoid spread of atypical lymphocytes in the epidermis. The results of an immunohistochemistry test led to a diagnosis of MEITL. This report points to the need for dermatologists and dermatopathologists to consider a possible diagnosis of MEITL when encountering similar cases.

Senescence Process in Primary Wilms' Tumor Cell Culture Induced by p53 Independent p21 Expression.

Wilms tumor (WT) is an embryonal tumor occurring in developing kidney tissue. WT cells showing invasive cancer characteristics, also retain renal stem cell behaviours. In-vitro culture of WT is hampered by limited replicative potential. This study aimed to establish a longterm culture of WT cells to enable the study of molecular events to attempt to explain its cellular senescence. Methods: Primary cell cultures from fresh WT tumor specimen were established. Of 5 cultures tried, only 1 could be propagated for more than 7 passages. One culture, identified as PSU-SK-1, could be maintained > 35 passages and was then subjected to molecular characterization and evaluation for cancer characteristics. The cells consistently harbored concomitant mutations of CTNNB1 (Ser45Pro) and WT1 (Arg413Stop) thorough the cultivation. On Transwell invasion assays, the cells exhibited migration and invasion at 55% and 27% capability of the lung cancer cells, A549. On gelatin zymography, PSU-SK-1 showed high expression of the matrix metaloproteinase. The cells exhibited continuous proliferation with 24-hour doubling time until passages 28-30 when the growth slowed, showing increased cell size, retention of cells in G1/S proportion and positive β-galactosidase staining. As with those evidence of senescence in advanced cell passages, expression of p21 and cyclin D1 increased when the expression of β-catenin and its downstream protein, TCF, declined. There was also loss-of-expression of p53 in this cell line. In conclusion, cellular senescence was responsible for limited proliferation in the primary culture of WT, which was also associated with increased expression of p21 and was independent of p53 expression. Decreased activation of the Wnt signalling might explain the induction of p21 expression.

Variants Associated with Infantile Cholestatic Syndromes Detected in Extrahepatic Biliary Atresia by Whole Exome Studies: A 20-Case Series from Thailand

Biliary atresia (BA) is the most severe form of obstructive cholangiopathy occurring in infants. Definitive diagnosis of BA usually relies on operative findings together with supporting pathological patterns found in the extrahepatic bile duct. In infancy, overlapping clinical patterns of cholestasis can be found in other diseases including biliary hypoplasia and progressive familial intrahepatic cholestasis. In addition, BA has been reported as a phenotype in some rare genetic syndromes. Unlike BA, other cholangiopathic phenotypes have their own established genetic markers. In this study, we used these markers to look for other cholestasis entities in cases diagnosed with BA. DNA from 20 cases of BA, diagnosed by operative findings and histopathology, were subjected to a study of 19 genes associated with infantile cholestasis syndromes, using whole exome sequencing. Variant selection focused on those with allele frequencies in dbSNP150 of less than 0.01. All selected variants were verified by polymerase chain reaction-direct sequencing. Of the 20 cases studied, 13 rare variants were detected in 9 genes: 4 in JAG1 (Alagille syndrome), 2 in MYO5B (progressive familial intrahepatic cholestasis [PFIC] type 6), and one each in ABCC2 (Dubin-Johnson syndrome), ABCB11 (PFIC type 2), UG1A1 (Crigler-Najjar syndrome), MLL2 (Kabuki syndrome), RFX6 (Mitchell-Riley syndrome), ERCC4 (Fanconi anemia), and KCNH1 (Zimmermann-Laband syndrome). Genetic lesions associated with various cholestatic syndromes detected in cases diagnosed with BA raised the hypothesis that severe inflammatory cholangiopathy in BA may not be a distinct disease entity, but a shared pathology among several infantile cholestatic syndromes.

Random skin biopsy for diagnosis of intravascular large B-cell lymphoma in a patient with hypoxemia and normal lung imaging

IVLBCL: intravascular large B-cell lymphoma I ntravascular large B-cell lymphoma (IVLBCL) is a very rare type of non-Hodgkin lymphoma in which tumor cells proliferate within the lumina of small blood vessels, particularly within capillaries, causing clinical symptoms. The clinical presentation of IVLBCL differs among geographic areas. For example, Asians more commonly present with fever, hepatosplenomegaly, thrombocytopenia, bone marrow involvement, and hemophagocytic syndrome and only rarely with central nervous system involvement or cutaneous lesions, which are more often seen in western populations. IVLBCL presenting as hypoxemia with no abnormal findings on chest computed tomography is rare, and only a few cases have been reported in which the disease was diagnosed by pulmonary microvascular cytology, open lung biopsy, or random transbronchial lung biopsy. There are a few reports suggesting the usefulness of the random or blind skin biopsy from normal-appearing skin for diagnosis of intravascular lymphoma.

Non-Hodgkin lymphoma in South East Asia: An analysis of the histopathology, clinical features, and survival from Thailand

Systemic reports on the descriptive epidemiology of non‐Hodgkin lymphoma (NHL) from Southeast Asia are scarce. A nationwide multi‐institutional registry was conducted to compare the histopathology, clinical features, and survival of Thai adult patients with NHL using large registries, especially those from Far East Asia (FEA). Using a web‐based registry system, 13 major medical centers from the 4 geographic regions of Thailand prospectively collected, from 2007 to 2014, the diagnostic pathology, according to the World Health Organization classification, 2008, clinical features and survival of 4056 patients who were newly diagnosed with NHL. The median age of the patients was 56 years (range, 16‐99 years). The male‐to‐female ratio was 1.3:1. From the total of 4056 patients, T/NK‐cell lymphoma (TNKCL) accounted for 12.6% of cases, and 5.1% had human immunodeficiency virus–associated lymphoma. The four leading histological subtypes were diffuse large B‐cell lymphoma, not otherwise specified (58.1%); follicular lymphoma (5.6%); extranodal mucosa‐associated lymphoid tissue lymphoma (5.2%); and peripheral T‐cell lymphoma, not otherwise specified (4.0%). With a median follow‐up duration of 46.1 months, the median overall survival of B‐cell NHL was significantly longer than that of patients with TNKCL (76.5 vs 28.8 months, P = .0001). Compared to FEA, the Thai registry had an approximately one‐half lower relative frequency of TNKCL; the prevalence of extranodal mucosa‐associated lymphoid tissue lymphoma was much lower than in Korea, and the frequency of extranodal TNKCL, nasal type, was strikingly low compared to China. It is concluded that while the median age of Thai patients with NHL was approximately a decade younger than for Caucasians, the long‐term survival rates for most histological subtypes were comparable. While the histological distribution generally complied with the characteristic Asian features, some differences from FEA were observed.

An Uncommon Cause of Small Bowel Bleeding from Appendiceal Carcinoma

Massive hematochezia caused by a small bowel lesion is a rare entity. Currently, video capsule endoscopy and balloon-assisted enteroscopy are effective in identifying the source of small intestine bleeding. Herein, we report a case of small bowel bleeding caused by a nonmucinous appendiceal adenocarcinoma with ileal invasion which was detected by video capsule endoscopy and single-balloon endoscopy. Despite the advanced disease stage with hepatic and peritoneal metastases, as of September 2016 the patient has had 8 years’ disease-free survival after surgical resection and chemotherapy.