Charin Ya‐In

Aims The aim of the present study was to compare treated lymphoma‐associated Epstein–Barr virus ( EBV )‐positive mucocutaneous ulcer ( EBVMCU ) and methotrexate ( MTX )‐associated EBVMCU . Methods and results Of a series of 15 Japanese patients (11 women, four men; median age 74 years, range 35–84 years), seven received MTX for the treatment of autoimmune disease and eight developed EBVMCU after treatment of malignant lymphoma [diffuse large B‐cell lymphoma ( n = 4) without EBV association, adult T‐cell leukaemia/lymphoma ( n = 2), angioimmunoblastic T‐cell lymphoma ( n = 1), and follicular lymphoma ( n = 1)]. Ulcers were observed in the oral cavity ( n = 11), gastrointestinal tract ( n = 2), and skin ( n = 2). All were histologically characterised by a mixture of EBV ‐positive large B‐cell proliferation and Hodgkin/Reed–Sternberg‐like cells on a polymorphous background. A total of 46% (6/13) had monoclonal immunoglobulin heavy chain gene rearrangement, but none had clonal T‐cell receptor gene rearrangement. Spontaneous regression occurred in 13 of 15 cases (87%); the other two cases (13%) achieved complete remission after treatment. Of two patients in the treated lymphoma‐associated subgroup, one developed multiple new ulcerative lesions on previously unaffected skin, and the other had a relapse of EBVMCU in the oral cavity. No significant clinicopathological differences were found between the subgroups. Notably, none of the patients died from EBVMCU . However, the treated lymphoma‐associated subgroup had lower overall survival ( P = 0.004) and a shorter follow‐up period ( P = 0.003) than the MTX ‐associated subgroup, owing to death from non‐associated causes. Conclusions Treated lymphoma‐associated EBVMCU , which is an indolent and self‐limited condition, must be recognised to avoid misdiagnosing it as a relapse of malignant lymphoma during treatment.

At the Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, 2,375 cases of breast lesions were sampled by fine-needle aspiration (FNA) from 1994-1999. Cytologic diagnoses were: benign (48%), suspicious for malignancy (5%), malignant (15%), and unsatisfactory (32%). Comparison with histology was possible in 721 cases. The diagnoses obtained by FNA showed a sensitivity of 84.4%, specificity of 99.5%, positive predictive value of 99.8%, negative predictive value of 84.3%, false-negative rate of 16.7%, false-positive rate of 0.5%, and overall diagnostic accuracy of 91.3%. We conclude that, in experienced hands, FNA of breast masses is reliable for diagnosis. Assessment of samples at the time of aspiration can reduce the number of inadequate specimens to near zero. Correlation of FNA results with clinical and radiologic findings can identify false-negatives and false-positives, ensuring optimal patient management. Many centers now recommend needle core biopsy instead of FNA. For regions such as ours, the added cost of this test would make it unavailable to many patients, which could delay a diagnosis of breast cancer. We advocate keeping FNA as a first-line diagnostic procedure, at least in areas under economic restrictions, in order to maximize the availability of health care to women with breast disease.

Abstract 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.

Penicillium marneffei is an opportunistic fungal infection that usually causes disseminated disease, mainly in immunocompromised individuals, especially those with HIV infection. Untreated cases are usually fatal. Diagnosis is traditionally made by biopsy and/or culture; successful diagnosis by fine needle aspiration (FNA) has only been reported once. We present eight cases of HIV-infected patients with lymphadenopathy caused by P. marneffei infection, in which the diagnosis was made by FNA. In all cases, intracellular and extracellular yeast forms were visualized, and the characteristic cross-septation of P. marneffei was highlighted by GMS staining. All diagnoses were confirmed by culture. Anti-fungal treatment for P. marneffei was initiated, resulting in marked clinical improvement. We conclude that a diagnosis of lymphadenopathy caused by P. marneffei can reliably be made by FNA. The diagnosis is more rapid than biopsy or culture, allowing rapid institution of therapy, particularly important in immunocompromised patients. In all our cases, not only were lymphoma and other causes of lymphadenopathy ruled out, but also the necessity for an open surgical biopsy was obviated. This can be especially beneficial to patients (e.g., three in our study) in which lymphadenopathy is confined to deep intra-abdominal nodes.

The aim of the present study was to determine the spectrum, frequency and demographics of bone tumors.A retrospective study of the 1,001 bone tumor specimens from the files at the Pathology Department of the Chiang Mai University Hospital, Thailand from 2000 to 2004.From the study, 41 were non-neoplastic mass lesions, and 960 were neoplastic, with 856 (89%) as primary and 104 (11%) as metastatic tumors. In the primary tumor group, 654 (76%) cases were of hematologic origin, and 202 (24%) were non-hematologic. The most common benign bone tumors were giant cell tumor (n = 37), osteochondroma (n = 25), and chondroma (n = 15). The most common malignant bone tumors were lymphoma-leukemia (n = 583), metastatic malignancy (n = 104), plasma cell myeloma (n = 71), and osteosarcoma (n = 58).The present study showed a higher frequency of osteosarcoma (68%), lower frequencies of chondrosarcoma (12%) and Ewing sarcoma (4%) among primary non-hematologic malignant bone tumors when compared with similar studies based on Western patients. Whether these differences reflect differences in the ethnic population or in practice patterns remains to be determined

Abstract Hairy cell leukemia variant (HCL-V) is a rare lymphoproliferative disorder. We report a case of HCL-V with an intrasinusoidal pattern of bone marrow involvement without interstitial or diffuse infiltration that is typical of HCL and its variant. The peripheral blood and bone marrow aspirates demonstrated abnormal lymphoid cells with cytoplasmic projections that were weakly positive for tartrate-resistant acid phosphatase cytochemical staining. Immunostaining of the bone marrow biopsy specimen showed that these cells were strongly positive for CD20, located within bone marrow sinusoids, and weakly positive for DBA44. By flow cytometry, these cells were positive for CD19, CD20, CD11c, and CD103, exhibited λ light chain restriction, and were negative for CD25. The patient was initially diagnosed as having splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma (SMZL) (World Health Organization designation) and treated with fludarabine followed by splenectomy with simultaneous liver biopsy. The pathologic analysis of the spleen revealed infiltration of red pulp by the critical cells without white pulp involvement, which is characteristic of HCL and HCL-V but not of SLVL (SMZL). This case illustrates an atypical marrow presentation of HCL-V and emphasizes the need to correlate all clinical and pathologic data, including tissue biopsy, in reaching a diagnosis.

Kimura's disease is a rare inflammatory disease that usually appears in head and neck region. We reported natural history of the disease and treatment outcome of radiotherapy (RT) in Chiang Mai University Hospital.A retrospective review was performed for all Kimura's disease patients treated with radiotherapy at our center between 2002 and 2017.A total of 20 patients with Kimura's disease were reviewed. There were 14 men and 6 women. All patients presented with the mass in head and neck region. Eleven patients were treated with a definitive intent with RT, 9 patients were treated with RT after recurrence from other modalities. All patients were treated with local external beam RT with 2 Gy per fraction to a median total dose of 30 Gy (range 30-40). The median follow-up time was 4 years (range 1-16.5 years). One patient died from HIV opportunistic infection after 1.5 year of radiation with complete response of Kimura's disease. Most of the patients responded to radiotherapy and controlled the disease at the time of analysis. Two patients had multiple recurrences at new areas outside radiotherapy field. Skin toxicity grade 1 was the most common late side effect which was found in 8 (44%) patients. We did not find severe late toxicity or second malignancy in this patient cohort.: Good local control of Kimura's disease can be achieved, with a radiation dose of 30-40 Gy, with insignificant late toxicities. We suggest that radiotherapy should be one of the treatments of choice for Kimura's disease both in primary or recurrence setting.

The widespread use of cross-sectional imaging techniques has resulted in increased detection of adrenal masses. The imaging characteristics of common adrenal masses such as adenoma, phaeochromocytoma and metastasis are well established. In this pictorial essay, the imaging features of unusual adrenal masses including cyst, lymphoma, adrenal carcinoma, myelolipoma, haemangioma, smooth muscle tumour, haematoma, and infection (acute tuberculous adrenitis and histoplasmosis) are presented. Computed tomography permits a diagnosis of cyst, acute or subacute haematoma and myelolipoma. Although the imaging features of other lesions are non-specific, imaging has an important role in the detection of these unusual adrenal masses, and in aiding their diagnosis and management.

Lymphocytic interstitial pneumonia (LIP) is an uncommon histopathologic entity characterized by infiltration of the interstitium and alveolar spaces of the lung by lymphocytes and other lymphoid elements. An increased incidence of LIP has been seen in the pediatric population, especially in children with acquired immune deficiency syndrome. Our previous study supports the notion that Langerhans cells (LCs) are reservoirs for Epstein-Barr virus (EBV) in lungs of human immunodeficiency virus (HIV) subtype E-infected pediatric LIP. To further understand the pathogenesis of LIP, we studied the relationship between EBV, the suggested causative agent of LIP and HIV-1 capsid protein p24, which play an important role in the interaction with host proteins during HIV-1 adsorption, membrane fusion, and entry in surgical lung biopsy-proven LIP from 9 vertically HIV subtype E-infected pediatric patients. The dominant microscopic feature of LIP demonstrated widespread widening of alveolar septum by mononuclear inflammatory cell infiltrate, mainly composed of mature lymphocytes and plasma cells surrounding airways and expanding to the lung interstitium. EBV-encoded RNA (EBER) in situ hybridization (ISH) and p24 immunohistochemistry, performed on formalin-fixed, paraffin-embedded tissue from open lung biopsy specimens, revealed positive intranuclear EBER signals and intracytoplasmic immunostains for p24 core protein in all 9 LIP cases. By combining ISH and immunohistochemistry, these results suggest that (i) EBV/p24-carrying cells are likely involved in the development of LIP, either directly or indirectly; (ii) LCs and related dendritic cells are the main reservoir of both EBV and HIV subtype E in pediatric LIP and possibly LCs may play an important role in the recruitment of inflammatory cell infiltrates, especially T cells into these tissues; (iii) coexpression of EBV/p24 in bronchioalveolar epithelium supports the hypothesis that these cells serve as a reactivation source for both viruses to achieve greater quantities in alveolar septum and interstitium around bronchioles. These results indicate a strong association between the presence of HIV core protein p24 and expression of EBV RNA transcripts (EBER). Interactions between LCs and related dendritic cells together with T cells are important for effective HIV and EBV replications. The coexpression of both viruses could be related to the evolution of pediatric LIP in HIV subtype E infection.

A 55-year-old man presented with a painless right scrotal mass for the past three months. Scrotal ultrasonography showed a large circumscribed hypoechoic mass with marked hypervascularity occupying almost the entire right testis. The epididymis and scrotal skin were normal. Right radical orchiectomy was performed. Histopathology revealed lymphoma, diffuse large B-cell type confined within the tunica albuginea. The patient made a good postoperative recovery. No evidence of lymphoma in other organs was demonstrated. We discuss the differential diagnosis of ultrasonographic intratesticular masses and highlight various cases of intratesticular lesions in this article.

To evaluate the role of cytology of sputum, bronchial brushing (BB), bronchial washing (BW), bronchoalveolar lavage (BAL) and fine needle aspiration cytology (FNA) in the diagnosis of lung cancer using histological material as a gold standard, a retrospective study was performed on cytological materials obtained from 243 patients with possible lung cancer. Of these, 160 had been confirmed histologically to have lung cancer. Cytological materials included in the study were 31 sputa, 123 BWs, 11 BBs and 36 BALs. Meanwhile, FNAs and concurrent gun biopsies (GBs) were performed on 23 patients clinically and histologically proved to have lung cancer. The overall sensitivity of sputum, BW and BAL was 0.222, 0.455 and 0.361, respectively. BB provided a significantly far superior sensitivity (0.800) than those of three former methods with p<0.05 by Fisher's exact test. FNA and GB seemed to provide greater sensitivity of 0.913 and 0.783, respectively. Although the complimentary role of various conventional cytological techniques is well recognized, bronchial brushing is the only single technique that significantly improved diagnostic yield. FNA and GB techniques should be encouraged due to their superior sensitivity.

Kimura's disease is a rare condition of chronic inflammatory disorder affecting the skin and subcutaneous tissue. It is predominantly in the head and neck region. The lesion is benign but may be persistent/ recurrent and difficult to eradicate. Several forms of treatment have been used, including surgical excision, intralesional and oral corticosteroid, cryotherapy and radiotherapy. The authors report eight cases with histopathology consistent with Kimura s disease who received radiation therapy as a primary treatment or secondary treatment for recurrence after surgical excision in the Division of Therapeutic Radiology and Oncology, Chiang Mai University. The prescribed radiation doses varied from 30-40 Gy. With the mean follow-up time of 21 months, all eight patients were still free from disease at the time of analysis.

Lymphoma can present with either lymphadenopathy or extranodal involvement. There are limited clinicopathological data pertaining to the occurrence of primary extranodal lymphoma (pENL) in Thailand. This was a retrospective study conducted at Chiang-Mai University Hospital from 2012 to 2016. Patients 18 years of age and over and with a diagnosis of pENL were enrolled onto study. Data related to clinical presentations, histology, stage, treatment and response were collected. There were 104 pENL patients with a median age of 63 years included. The most common presentation was gastrointestinal symptoms (41%), followed by ear, nose, and throat symptoms (35%). Diffuse large B-cell lymphoma (DLBCL) was the most common morphological subtype (60%), followed by marginal zone lymphoma (15%). The majority of patients presented with stage II disease (55%). The five-year overall survival rate was 71%. The factors associated with mortality were hemoglobin &lt;7 g/dL, B-symptoms and LDH above upper normal limits. This study illustrated that lymphoma can present at various extranodal sites. Gastrointestinal symptoms were the most common presentations and DLBCL was the most common subtype of pENL.

Introduction: Vulnerable plaque or soft plaque potentially increases risk of stroke. Accurate plaque characterization is a demand for treatments. To date, magnetic resonance imaging (MRI) using multiweighted images, T1 weighted (T1W), T2 weighted (T2E), and proton density weighted (PDW), is one of the best available tools. Due to the spin-spin relaxation property, different tissues reveal differences of T2s. We proposed T2 mapping for analysis plaque components, and to examine the possibility of using T2 mapping for carotid atherosclerotic plaque characterization. Materials and methods: The 1.5 Tesla Philips, Acheiva Nova Dual, MRI scanner was employed to this study. T2 mapping images of a phantom made from 4 types of tissues were compared with T1W, T2W, and PDW images in term of accuracy. The comparisons were also performed on 4 different specimens and 8 volunteers diagnosed with carotid atherosclerosis. Axial images were acquired along the length of the phantoms with a scanning protocol including Spin echo-multi-echoes pulse sequence at 8 echo time (8TEs) from 15 ms. to 120 ms, inter-echo time 15 ms, field of view (FOV) 140x140 mm., matrix size 200x219, flip angle 90 degree, number of signal average (NSAs) 4, repetition time (TR) 1,333 ms, and slice thickness 3 mm. For the 8 human volunteers, axial images were acquired at the narrowest stenosis of the carotid artery with a scanning protocol slightly modified from that of the phantoms to suit for human scanning. The axial images from the 8 TEs were fit for T2 in each pixel with a simple mono-exponential model for generating T2 mapping. The accuracy of the images at the same location between the T2 mapping and the 3 weighted images were compared. Results: The results from 4 known types of tissues showed that 4 major groups of tissues were classified with T2 mapping. Each group of the classification has a frequency over 60% of the maximum frequency, while T1W, T2W and PDW images were classified with intensity contrast into 2, 2 and 3 groups, respectively. However, the study in the specimen phantoms and the human volunteers were not validated due to little concordance of slice location between the images and those of the pathology section. Conclusions: The T2 mapping showed more accurate classification in known types of tissue phantom compared to those of the T1W, T2W and PDW. However, the study in humans may need further study. Bull Chiang Mai Assoc Med Sci 2014; 47(1): 37-44

Natesirinilkul, Rungrote MD*; Charoenkwan, Pimlak MD*; Tantiprabha, Watcharee MD*; Pruksachartkun, Chulabhorn MD*; Ya-in, Charin MD† Author Information

Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Presenting with hepatosplenomegaly, fever, cytopenia without significant lymphadenopathy, most patients are young men with poor outcomes. Here is the report of two cases of HSTCL from Maharaj Nakorn Chiang-Mai Hospital, Thailand. Both patients were middle-aged men presented with prolonged fever, hepatosplenomegaly and cytopenia. Abnormal lymphoid cells, not demonstrated by flow cytometry, were microscopically revealed in the patients’ bone marrow. The diagnosis of HSTCL was based on the histopathologic section obtained from splenectomy and liver biopsy. Both patients received cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) regimen initially while one of them was salvaged with etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP) and methotrexate, high-dose cytarabine, methylprednisolone (cycle B of hyperCVAD) regimen. They responded poorly to chemotherapy and succumbed to severe sepsis. The presented cases confirmed that HSTCL is very difficult to diagnose and current treatment modalities appear to be ineffective

Objective: To assess the role of routine multiparameter flow cytometry, for lineage assignment of leukemic cells in patients with acute leukemia. Materials and Methods: One hundred cases of adult and children patients diagnosed with acute leukemia admitted at Maharaj Nakorn Chiang Mai Hospital during 2010 were reviewed. Bone marrow samples were immunophenotyped by multiparameter flow cytometry compared to morphology. Results: In our retrospective analysis of 100 cases, morphology established lineage in all cases (100%). However, immunophenotyping significantly indicated lineage assignment difference from morphology in 16 cases (16%) with p <0.001. The first group of 8 cases was reported to be lymphoid from previously reported myeloid. The second group of 8 cases was confirmed to be myeloid from previously reported lymphoid. Conclusion: The results addressed the significant benefit and supported routine application of immunophenotyping in the diagnosis of acute leukemia.

A 58 years old woman presented with prolonged fever with headache and significant weight losswithout abnormal finding on physical examination. The initial laboratory investigations revealed hemoglobin 9.3 g/dL, evidence of autoimmune hemolytic anemia on peripheral blood smear, urine protein 205 mg/24 hours, positive ANA, MRI brain showed subacute infarction at right-sided of pons. She was treated with high dose steroid as autoimmune disease but still had high fever. The patient developed dyspnea on exertion, pittingedema and severe hypoalbuminemia. The bone marrow aspiration showed increasing of histiocytes withoutabnormal cells detected. The CT chest include abdomen was unremarkable. The FDG-PET/CT scan was doneand revealeddiffuse increased bone marrow uptake and splenomegaly with diffused uptake. Then, pathologicalreport of bone marrow and random skin biopsy demonstrated the large B cell within small vasculature with CD20 positive compatible with intravascular large B cell lymphoma

A 45-year-old woman presented with bilateral palpable breast masses, which were clinically suspicious of either mammary carcinomas or phyllodes tumors. Fine needle aspiration (FNA) study suggested low-grade lymphoma. Histological and immunohistochemical studies of an incisional biopsy specimen of the left breast lesion confirmed the diagnosis of low-grade B-cell lymphoma. Computerized tomographic scans of chest and abdomen revealed multiple lymphadenopathy in the mediastinum and intra-abdomen. After receiving chemotherapy, marked reduction in size of both breast masses and the internal lymph nodes was observed. Primary lymphomas of the breast are rare, particularly those with bilateral involvement. FNA is an inexpensive diagnostic tool for breast lumps that can reliably distinguish carcinoma, sarcoma and lymphoma. Although it is often difficult for the cytological study to differentiate low-grade lymphoma from reactive lymphoid proliferation, FNA results in combination with clinical and radiological studies (triple testing) generally provide guidance for appropriate investigations, and helps avoiding unnecessary major operation.