Wasana Kanoksil

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.

Therapy-related myelodysplastic syndrome/acute myeloid leukemia following fludarabine therapy for non-Hodgkin lymphoma and chronic lymphocytic leukemia in Thai patients

Therapy related myelodysplastic syndrome (t-MDS) and secondary acute myeloid leukemia (AML) are seriously late complications of the use of alkylating agents, topoisomerase II inhibitors, and other chemotherapies. Deoxyribonucleic acid (DNA) damage that leads to chromosomal deletions or balanced translocations partly cause t-MDS. Deletions of chromosomes 5 and 7 are also commonly found in alkylator-associated MDS/AML. Over the last half decade, fludarabine has been widely used as frontline therapy for indolent B-cell lymphomas and chronic lymphocytic leukemia (CLL). The incidence of t-MDS/AML following fludarabine-based therapies is 0.5%, 3.5%, 9%, and 2% of patients receiving treatment with fludarabine alone, fludarabine plus chlorambucil, fludarabine combined with cyclophosphamide, and the combination of rituximab, fludarabine, and cyclophosphamide, respectively [1,2]. Nevertheless, the risk factor for fludarabine-induced t-MDS/AML has not been established. We therefore performed a retrospective study to analyze the predicting factors for t-MDS/AML in patients with B-cell lymphomas and CLL treated with fludarabinebased therapy. Thirty-eight patients with B-cell lymphomas and CLL receiving fludarabine-based therapy at Ramathibodi Hospital between January 2003 and December 2008 were included in the analysis. This included all patients with CLL treated with fludarabine at our hospital, with the following exceptions: patients who died within 1 year after fludarabine therapy from non-MDS causes, or patients who received treatment with stem cell transplant, immunoradiotherapy, or a salvage regimen, such as ICE (ifosfamide, carboplatin, etoposide), ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin), IMVP-16 (ifosfamide, methotrexate, etoposide), and hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), were excluded. Thirty-eight patients were treated with fludarabine (F) 30 mg/m/day intravenously (i.v.) for 3 consecutive days, and cyclophosphamide was included for 33 patients receiving the FC regimen. The doses of cyclophosphamide were as follows: cyclophosphamide 600 mg/m/day i.v. on day 1 (nine patients), or cyclophosphamide 200 mg/m/day i.v. for 3 consecutive days (24 patients). Rituximab 500 mg/day

Fine-Needle Aspiration Biopsy of Langerhans Cell Histiocytosis of Thyroid Gland

A 54-year-old postmenopausal woman presented with progressive thyroid enlargement for 1 year. Thyroid ultrasonography showed multinodular enlargement with an 8 6-cm isoechoic mass and a 6 5-cm hyperechoic mass on the right and left lobes, respectively. Thyroid function testing, including free T4 of 0.48 ng/dL (normal range, 0.7–1.48), free T3 of 3.12 pg/mL (1.71–3.71), and TSH of 5.39 mIU/L (0.35–4.94), showed primary thyroid failure with an insufficient pituitary response, suggesting both primary and secondary hypothyroidism. Fine-needle aspiration biopsy (FNAB) was performed on the right lobe and reported as Langerhans cell histiocytosis (LCH) (Figure 1). The diagnosis of LCH is confirmed by positive immunohistochemical study for S-100 and CD1a. Further investigations revealed hypopituitarism: morning cortisol, 2.5 g/dL (5–25); FSH, 3.92 IU/L (26–133); LH, 0.14 IU/L (10–26); and IGF-1, 55 ng/mL (87–238). An elevated prolactin of 139.17 ng/mL (5.18–26.53) suggested a prolactinoma, infundibular compression, or bilateral median eminence dysfunction. Central diabetes insipidus was diagnosed based on polyuria, polydipsia, depressed urine osmolarity of 113 mOsm/kg, and elevated serum osmolarity of 295 mOsm/kg. Magnetic resonance imaging pituitary showed a well-defined mass of 1.2 0.8 1 cm involving median eminence of the hypothalamus, superior aspect of the pituitary stalk, extending to the floor of the hypothalamus (Figure 2). The final diagnosis was multisystem LCH. The patient was administered chemotherapy of vinblastine 6 mg/m every week, prednisolone 40 mg/m for 4 weeks then tapered down, and levothyroxine 50 g/d. After seven cycles of chemotherapy, goiter size had decreased to 20 g by palpation, and symptoms of central diabetes insipidus had improved. LCH mostly involved bone, skin, pituitary, liver, spleen, lungs, lymph nodes, and the central nervous system (1). The most common endocrine manifestation of LCH is central diabetes insipidus. LCH of the thyroid is extremely rare and can be presented in localized or multisystem disease (2, 3).

Comparison of diagnostic performances among bronchoscopic sampling techniques in the diagnosis of peripheral pulmonary lesions

BACKGROUND There are many sampling techniques dedicated to radial endobronchial ultrasound (R-EBUS) guided flexible bronchoscopy (FB). However, data regarding the diagnostic performances among bronchoscopic sampling techniques is limited. This study was conducted to compare the diagnostic yields among bronchoscopic sampling techniques in the diagnosis of peripheral pulmonary lesions (PPLs). METHODS A prospective study was conducted on 112 patients who were diagnosed with PPLs and underwent R-EBUS-guided FB between Oct 2012 and Sep 2014. Sampling techniques-including transbronchial biopsy (TBB), brushing cell block, brushing smear, rinsed fluid of brushing, and bronchoalveolar lavage (BAL)-were evaluated for the diagnosis. RESULTS The mean diameter of the PPLs was 23.5±9.5 mm. The final diagnoses included 76 malignancies and 36 benign lesions. The overall diagnostic yield of R-EBUS-guided bronchoscopy was 80.4%; TBB gave the highest yield among the 112 specimens: 70.5%, 34.8%, 62.5%, 50.0% and 42.0% for TBB, brushing cell block, brushing smear, rinsed brushing fluid, and BAL fluid (BALF), respectively (P<0.001). TBB provided high diagnostic yield irrespective of the size and etiology of the PPLs. The combination of TBB and brushing smear achieved the maximum diagnostic yield. Of 31 infectious PPLs, BALF culture gave additional microbiological information in 20 cases. CONCLUSIONS TBB provided the highest diagnostic yield; however, to achieve the highest diagnostic performance, TBB, brushing smear and BAL techniques should be performed together.

Diagnóstico de lesiones pulmonares periféricas con broncoscopia bajo guía de ecografía endobronquial radial

INTRODUCTION The diagnosis of peripheral pulmonary lesions (PPLs) is a challenging task for pulmonologists. Radial probe endobronchial ultrasound (R-EBUS) has been developed to enhance diagnostic yield. The objective of this study was to evaluate the effectiveness of R-EBUS in the diagnosis of PPLs. METHODS A retrospective study was conducted on 174 patients diagnosed with PPLs who underwent EBUS-guided bronchoscopy. Histological examination of specimens obtained by transbronchial lung biopsy (TBLB) and cytological examinations of brushing smear, brush rinse fluid and bronchoalveolar lavage fluid (BALF) were evaluated for the diagnosis. RESULTS The mean diameter of the PPLs was 25.1 ± 10.7 mm. The final diagnoses included 129 malignancies and 45 benign lesions. The overall diagnostic yield of EBUS-guided bronchoscopy was 79.9%. Neither size nor etiology of the PPLs influenced the diagnostic performance of EBUS-guided bronchoscopy (82.9% vs. 74.6% for PPLs>20mm and PPLs≤20mm; p=0.19, and 82.9% vs. 71.1% for malignancy and benign diseases; p=0.09). TBLB rendered the highest yield among these specimens (69.0%, 50.6%, 42.0%, and 44.3% for TBLB, brushing smear, brush rinse fluid, and BALF, respectively; p<0.001). The combination of TBLB, brush smear, and BALF provided the greatest diagnostic yield, while brush rinse fluid did not add benefits to the outcomes. CONCLUSION R-EBUS-guided bronchoscopy is a useful technique in the diagnosis of PPLs. To achieve the highest diagnostic performance, TBLB, brushing smear and bronchoalveolar lavage should be performed together.

Pitfall in immunohistochemical staining for thyroglobulin in case of thyroid metastasis from lung carcinoma

A 73-year-old female presented with an enlarging neck mass over the last 2 years. She then started experiencing hoarseness, dysphagia, and weight loss for 5 months. Physical examination showed an irregular and hard consistency mass with a diameter of 4 cm occupying the left lobe and isthmus of the thyroid gland. Fine-needle aspiration biopsy (FNAB) was performed and the cytology specimen revealed sheets of neoplastic cells with enlarged, hyperchromatic, slightly pleomorphic nuclei, prominent nucleoli, and brownish pigment inside the tumor cells [Figure 1a]. The definitive diagnosis could not be made from cytology alone. Immunohistochemical staining was requested with positive results for thyroglobulin [Figure 1b], thyroid transcription factor 1 (TTF-1) [Figure 1c], but negative for calcitonin. Figure 1 (a) Fine-needle aspiration thyroid showed a background of cystic lesion (foamy cells) with few of neoplastic cells and a sheet of degenerative follicular cells (Papanicolaou stain, ×400), (b) cell block preparation showed the immunoreactivity ...

Postgraduate Education Corner: Contemporary Reviews in Critical Care MedicineA 76-Year-Old Man With Anemia, Bone Pain, and Progressive Dyspnea

76-year-old man presented with left-sided hip pain radiating to the leg and foot for 4 weeks. He was a former smoker. The patient’s medical history included coronary artery disease, benign prostatic hypertrophy, and mild chronic renal impairment (serum creatinine, 1.5 mg/dL). Other previous blood chemistry tests and chest radiographs obtained 6 months earlier were unremarkable. The plain radiographs of the lumbosacral spine revealed only mild degenerative changes. Two weeks later, the patient developed progressive dyspnea and dry cough without fever, orthopnea, or paroxysmal nocturnal dyspnea. On examination, he looked distressed and was tachypneic. Fine crepitations were heard bilaterally in the lower lungs. Both legs were edematous. There was a hard, nonpainful palpable mass at the sternum. Other physical examinations and neurologic signs were normal.

A 76-Year-Old Man With Anemia, Bone Pain, and Progressive Dyspnea

76-year-old man presented with left-sided hip pain radiating to the leg and foot for 4 weeks. He was a former smoker. The patient’s medical history included coronary artery disease, benign prostatic hypertrophy, and mild chronic renal impairment (serum creatinine, 1.5 mg/dL). Other previous blood chemistry tests and chest radiographs obtained 6 months earlier were unremarkable. The plain radiographs of the lumbosacral spine revealed only mild degenerative changes. Two weeks later, the patient developed progressive dyspnea and dry cough without fever, orthopnea, or paroxysmal nocturnal dyspnea. On examination, he looked distressed and was tachypneic. Fine crepitations were heard bilaterally in the lower lungs. Both legs were edematous. There was a hard, nonpainful palpable mass at the sternum. Other physical examinations and neurologic signs were normal.

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.

Peniciliosis endobronquial: presentación de un caso y revisión de la literatura

Penicilliosis is an opportunistic infection in HIV-infected and other immunocompromised patients mostly in Southeast Asia, Southern China, Hong Kong, and Taiwan, with respiratory manifestations in about one-third of patients. We report the case of a 26-year-old non-HIV immunocompromised patient presenting with an airway obstruction caused by penicilliosis, together with a review of the literature of this rare condition.