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Although, in the thyroid field, there have been several internationally standard diagnostic and management guidelines for practitioners from every country to follow but there is still variation among physicians across the globe in taking care of patients and pathology specimens with thyroid nodules due to dissimilar backgrounds of each place. Thailand is one among several countries that tries to maintain standard of care to meet international requirements although, with some limitations, not all recommendations are followed. To understand how approaches of thyroid nodules are performed throughout the country and how the healthcare system of the whole kingdom is managed including what major current limitations, the authors conducted a survey among physicians consisting of surgeons, radiologists and pathologists who are involved in the management of the thyroid lesions by personal phone contact and custom online questionnaires. Performances of fine needle aspiration of different institutes are also evaluated by analyzing the data from available publications and compared their results with other series from the literature. Shortage of pathologists and un-equal resource allocation are the major problems concerning administrative aspect while a lack of awareness in new terminologies or diagnostic systems (e.g., NIFTP, UMP, Bethesda, TI-RADS) among physicians, particularly clinicians, are the problems of training and continuous medical education. Another point of concern is a rather poor performance in fine needle aspiration from the Thai series in which there are high rate (30.5%) of non-diagnostic category (Bethesda I) and false negativity as demonstrated by relatively high risk of malignancy (9.6%) in Bethesda II compared with other series from the literature. Regarding molecular studies, despite their usefulness in improving diagnostic accuracy, especially for cytology specimens, these ancillary tools are not routinely used in our practice since they are available in only few referral centers. This review provided a background information of the perspective on how thyroid nodules are managed in the Thai settings., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-395). The series “Asian and Western Practice in Thyroid Pathology: Similarities and Differences” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

Background: Hürthle cell-rich nodules (HCNs) encompass non-neoplastic to malignant lesions. There is paucity of literature on the frequency distribution of HCNs among Bethesda categories, histologic follow-up, risk of malignancy (ROM), and risk of neoplasia (RON). The objective of this retrospective, multi-institutional study was to determine the prevalence of the cytologic diagnostic category and surgical outcomes of patients with HCN., Methods: Nine tertiary health centers representing 6 Asian countries participated. Cases were retrieved from respective databases. The Bethesda System for Reporting Thyroid Cytopathology was used. Cytology results were correlated with surgical diagnoses., Results: Of 42,190 thyroid aspirates retrieved, 760 (1.8%) had a Hürthle cell predominance. Most (61%) were categorized as atypia of undetermined significance/follicular lesion of undetermined significance, Hürthle cell type" (AUS-H); 35% were categorized as follicular neoplasm, Hürthle cell type (FN-H); and 4% were categorized as suspicious for malignancy (SFM). Histologic follow-up was available for 288 aspirates (38%). Most were benign on resection (66%), and the most common histologic diagnosis was Hürthle cell adenoma (28.5%). The ROM for AUS-H, FN-H, and SFM, as calculated on resected nodules, was 32%, 31%, and 71%, respectively; and the RON was 47%, 81%, and 77%, respectively. The 5 institutions that had an AUS-H:HCN ratio below 0.5 diagnosed HCN less frequently as AUS-H than as FN-H., Conclusions: This is the largest, contemporary, multi-institutional series of HCNs with surgical follow-up. Although there was wide interinstitutional variation in prevalence and surgical outcomes, there was no significant difference in the ROM among institutions. The categories AUS-H and FN-H had a similar ROM for resected nodules., (© 2019 American Cancer Society.)

Thyroid carcinoma is one of the leading malignancies in Thailand increasingly prevalent in the female population. Fine-needle aspiration (FNA) cytology is a widely used diagnostic tool for evaluation of thyroid nodules and thyroid cancer. Thyroid FNA is a routine procedure universally performed in Thai hospitals by a variety of clinical specialists. Manual guidance is the first-line choice complemented by ultrasound assistance in selected cases. Despite national guidelines recommendations, the diagnostic criteria and terminology of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was slowly adopted in the local settings. Currently, the Bethesda system is actively promoted by the local professional societies as a uniform reporting system. Experience with thyroid FNA has been rarely reported to date-only a handful of publications are available in local journals. Our review, in addition to presenting various aspects of thyroid FNA in Thailand, established for the first time national references for a certain statistical outputs of TBSRTC based on the original multi-institutional cohort. The risk of malignancy in 2,017 operated thyroid nodules collected from three tertiary thyroid cancer centers was 21.7%, 14.7%, 35.9%, 44.4%, 76.7%, and 92.6% for categories I to VI, respectively. The malignancy risk in several diagnostic categories (II to IV) was higher than the risk estimated by TBSRTC and recent meta-analysis studies. We endorse the use of uniform terminology of the Bethesda system in Thailand, which will help facilitate communication among diverse medical professionals involved in the management of patients with thyroid nodules, to share local experience with the international audience.

Objectives: To estimate the prevalence and factors associated with Human Papillomavirus (HPV) infection, HPV genotypes and cytological/histological high-grade (HSIL+/CIN2+) lesions., Methods: We conducted a cross-sectional study within a prospective cohort of HIV-infected women on combination antiretroviral therapy (cART). Cervical specimens were collected for cytology and HPV genotyping (Papillocheck ® ). Any women with High-Risk-HPV (HR-HPV), and/or potentially HR-HPV (pHR-HPV) and/or ASC-US or higher (ASC-US+) lesions were referred for colposcopy. Factors associated with HR-HPV infection and with HSIL+/CIN2+ lesions were investigated using mixed-effects logistic regression models., Results: 829 women were enrolled: median age 40.4 years, on cART for a median of 6.9 years, median CD4 cell-count 536 cells/mm3, and 788 (96%) with HIV-viral load<50copies/mL. Of 214 (26%) infected with HPV: 159 (19%) had ≥1 HR-HPV, of whom 38 (5%) HPV52, 22 (3%) HPV16, 9 (1%) HPV18; 21 (3%) had pHR-HPV, 34 (4%) low risk-HPV infection, and 56 (26%) had multiple genotypes. Younger age, low CD4 cell-counts and low education were independently associated with HR-HPV infection. 72 women (9%) had ASC-US+ and 28 (3%) HSIL+/CIN2+ lesions. HR-HPV infection was independently associated with HSIL+/CIN2+ lesions., Conclusion: The prevalence of HPV infection and of cervical lesions was low. The HPV genotype distribution supports the use of 9-valent vaccine in Thailand., (Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the performance of Papanicolaou smear screening in Thailand at the national level, and to propose recommendations for continuing quality control., Study Design: This study was conducted by The Thai Society of Cytology and involved 124 laboratories in 76 provinces during 2010-2014. Random sampling suggested recalling of 10% of slides defined as negative at routine screenings (10% random rescreening [R10] model) directly from the reading unit., Results: Out of 330,075 smears covered by the rescreening project throughout its 5-year duration, the rates of abnormal, unsatisfactory, and normal results were 0.63, 1.82, and 97.55%, respectively. Abnormal findings were largely represented by ASC-US (54%) and L-SIL (21%). The average false-negative rate (FNR) measured at the level of L-SIL and higher was 13.8%., Conclusion: The national project was developed to address the accuracy of cervical cancer screening and to promote internal quality assurance based on the R10, on-site surveys, and education. The major output parameters of this study (FNR and number and distribution of abnormal cases on rescreening) improved significantly in the main phase of the project (2012-2014), after revising substantial logistics issues encountered during the first 2 years of this study. This project provided objective measurable evidence related to the quality of cytology-based cervical cancer screening in Thailand., (© 2017 S. Karger AG, Basel.)

The hypoglycemic activities of nine sub-fractions from the methanolic leaf crude extract of Anisopus mannii were investigated in normoglycemic and alloxan-induced diabetic mice. The methanolic sub-fraction M at 400 mg/kg bw showed significantly (p<0.05) high reduction in fasting blood glucose (FBG) at 27.36 and 65.57% in normoglycemic and diabetic mice, respectively. In acute toxicity test, M at 2,000 and 5,000 mg/kg bw showed reduction in blood urea nitrogen and creatinine level, elevations in aspartate transaminase, alanine transaminase and total bilirubin levels, as well as the body weights. The weight-ratios of kidney and liver to the body weight of the mice fed with these doses of M were reduced with no sign of histopathological alteration. The M at 250 mg/kg bw significantly reduced the FBG levels in a postprandial study. The hypoglycemic effect of M was eliminated when co-administered with isosorbide dinitrate or nifedipine indicating the induction of insulin secretion via K+ ATP-dependent channels. The UV/HPLC analysis of M indicated saponin at 7.7 mg/g. This study confirmed the traditional use of A. mannii for diabetes mellitus and the potential for the further development as a novel hypoglycemic drug.

Background: Oral lichen planus (OLP) is a chronic inflammatory lesion in oral mucosa. Reticular (OLP-R) and erosive (OLP-E) types of OLP are the common forms that have been found in dental clinics. The aim of this investigation is to determine the correlation between neurogenic inflammation and nociception associated with OLP-R and OLP-E., Materials and Methods: The oral mucosal lesions from six patients with OLP-E, four with OLP-R and three with noninflamed oral mucosa, which represent normal mucosa, were identified by morphometric analysis of nerve fibers containing immunoreactive protein gene product (PGP) 9.5. The level of inflammation was measured with hematoxylin and eosin staining and the level of nociception was analyzed with visual analog scale measurement., Results: We found that 1) an increase in peripheral innervation was related to the size of the area of inflammatory cell infiltration from both OLP-R and OLP-E; 2) the pattern of PGP 9.5-immunoreactivity among OLP-R and OLP-E was not significantly different (P=0.23); and 3) the correlation between nociception and an increase in PGP 9.5-immunoreactivity was not found in OLP-E and in OLP-R., Conclusions: Our findings suggest that an increase in peripheral innervation may lead to increased inflammation, which is part of the immunopathogenesis of OLP. Differences in nociception between OLP-R and OLP-E arise from the pathogenesis of each lesion, not from the differences in peripheral innervation.

Vaccination has been underway in several countries for sexually inactive young girls or women against HPV 16 and 18 to prevent them from infection of these HPV types and concurrent cancer development. However, uterine cervical cancers may remain uncontrolled among some Asian countries, where other types of HPV infection are more frequent. A sensitive cancer screening system would remain important for detection of the earlier stage cervical cancers in Asian countries. In this study, 130 cytotechnologists (CTs) in Asian countries (Taiwan 80, Japan 18, Korea 15, Thailand 11, Singapore 3, Bhutan 2, and Mongolia 1) participated in the vote. Selected 10 cervical Pap smears that would be adequate to identify the diagnostic clues especially for atypical squamous cells (ASC) with two or three representative pictures for each case were displayed on the website. The percentages of consistent diagnosis voted by certified CTs with ≥5 years of experience were compared among 10 cervical cases or among Asian countries enrolled. As results, low consistency for ASC cases and high consistency for squamous intraepithelial lesion (SIL) were observed. Examining specimens for the diagnostic clues of ASC in TBS is crucial to maintain the high sensitivity and positive predictive value of SIL in Asian countries., (Copyright © 2010 Wiley-Liss, Inc.)

Objective: A modified liquid-based techniques known as the "LiquiPrep (LP) system" requires neither expensive equipment nor complicated specimen preparation. The aim of this study was to assess the applicability of the LP for use in a developing country., Methods: Cervical cytology specimens were collected from 777 women, using the Cervex-Brush. The brush was first smeared on a glass side for conventional Papanicolaou (CP) stain, and then immersed in preservation fluid for LP preparation. Cytologic interpretations were classified into four categories: 1) no atypical cells, 2) atypical squamous epithelial cells (ASC), 3) definite epithelial cell abnormality, and 4) unsatisfactory specimen. Interobserver variability was tested using weighted kappa statistics., Results: An LP specimen cost $9 per case compared to $3 per case for a conventional Pap smear. The time to learn the technique was only a few days. Forty six (5.92%) specimens by LP were unsatisfactory. The overall agreement between cytopathologists was 96.7% (weight kappa=0.62), with 95.6% (weight kappa=0.44) for the cases enrolled earlier, increasing to 97.9% (weight kappa=0.78) for the cases enrolled later., Conclusions: In summary, after a short learning curve, interobserver reproducibility of LP smear was near perfect. This feature of the LP, together with the relatively low cost and simple protocol, makes it quite suitable for cervical cytology screening in developing countries. Moreover, with this technique, some of each sample can be reserved for additional studies such as HPV detection and subtyping.

Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma., Experimental Design: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array., Results: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently from the activation of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent signaling route stimulating mTOR., Conclusions: These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients.

Objective: To summarize the epidemiologic features of osteosarcoma., Material and Method: One hundred and twelve cases of osteosarcoma were collected retrospectively from the Pathology Department of the Chiang Mai University Hospital, Thailand between 1995 and 2005., Results: From the present study, there were 14 cases in average, annually, since 2002. Seventy-seven percent of cases were from the upper north Thailand, the region serviced by Chiang Mai University Hospital. The male:female ratio was 1.3:1 and 86% of cases occurred within the first three decades of life. The majority of cancer was found in the long bones (83%) and the majority of lesion was around the knee (68%). Conventional and telangiectatic osteosarcoma accounted for 85% and 8% of cases, respectively., Conclusion: The authors have summarized some epidemiologic features of osteosarcoma. The authors found the relatively high frequency of telangiectatic osteosarcoma around the upper part of north Thailand These results give an initial picture to the national health provider section for planning personnel, medical and supportive equipment, and funding for the care of osteosarcoma patients. Nationwide co-operation in registering osteosarcoma patients would provide more complete data on this tumor in Thailand and promote the establishment of standardized treatment protocols.

We have previously used agarose gel electrophoresis and immunoblotting to qualitatively measure serum MUC5AC mucin for diagnosing cholangiocarcinoma. In this study, we developed a quantitative determination of serum MUC5AC by sandwich ELISA using MUC5AC mucin monoclonal antibody and soybean agglutinin. A cut-off value of the absorbance 0.074 was obtained from a complete statistical Receiver Operating Characteristic curves with an area under the curve=0.8141. The assay could discriminate cholangiocarcinoma patients from the controls with 71% sensitivity and 90% specificity. The test is simple to perform, reproducible, and probably used for detecting cholangiocarcinoma in a high-risk group or suspected patients.

Objective: The aim of the present study was to determine the spectrum, frequency and demographics of bone tumors., Material and Method: 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., Results: 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)., Conclusion: 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

Introduction: Limb loss has a devastating effect on patients. To know the underlying causes of limb amputation would be helpful in planning public health strategies in the country. The objectives of this study are (1) to identify the primary causes and the feature of limb amputations in the setting of a university hospital, and (2) to study the time trends of the causes of limb amputation over a period of 5 years., Materials and Methods: The clinical and pathological data from 216 amputated limbs submitted to the Pathology Department of Chiang Mai University Hospital from 2000 to 2004 were reviewed., Results: Of these, 188 cases were first time amputations, and 28 cases were repeat amputations. The 188 first amputated specimens included 23 upper limbs (12%) and 165 lower limbs (88%), from 115 male (61%) and 73 female (39%) patients. Dysvascular (46%), tumor-related (36%), and infection-related (10%) amputations were the three most common scenarios. The rate of amputation was high in 2004 (32%) owing to an unexpected increase in the numbers of dysvascular amputation. Atherosclerosis accounted for at least 52% of dysvascular amputations. The leading cause of tumor-related amputations was sarcoma (72%), almost half of which were osteosarcomas. The major cause of lower limb amputation was dysvascular (51%) whereas that of upper limb amputation was tumor related (61%). Subgroup analysis of the major limb amputations revealed that 44% were tumor related, 39% were dysvascular, and 8% were infection-related causes. The proportion of major limb losses in the tumor-related group (87%, 59/68) was significantly higher than those in the dysvascular group (62%, 53/86) (P = 0.001). In addition, the proportion of upper limb losses in the tumor-related group (21%, 14/68) was significantly greater than those in the dysvascular group (2%, 2/86), (P < 0.001). The causes of 28 repeat amputations were similar, i.e., dysvascular (61%), tumor related (29%), and infectious related (7%)., Conclusion: (1) Atherosclerosis, a potentially preventable disease is responsible for the great proportion of limb losses in Northern Thailand; (2) the numbers of dysvascular amputation seem to be increasing; (3) tumor, especially sarcoma, is the most common cause of major limb amputations as well as upper limb loss.

Introduction: This study aims to correlate fine-needle aspiration specimens diagnosed as C3 (atypical, probably benign) and C4 (suspicious, probably malignant) with histology and mammography, and to evaluate these two cytology categories in terms of diagnostic usefulness and patient management., Methods: All fine-needle aspiration (FNA) specimens in categories C3 or C4 at the Maharaj Nakorn Chiang Mai Hospital, Thailand between 2000-2004 were reviewed. Results were correlated with available histological and mammographical studies., Results: 148 FNA specimens were identified, comprising 43 category C3 and 105 category C4. Histology was available in 90 cases. 14 (64 percent) C3 cases showed benign histology on biopsy and eight (36 percent) were malignant. 13 (19 percent) C4 cases were benign on biopsy, whereas 55 (81 percent) were malignant. Mammographical studies were available in 56 of the histologically-proven cases. All seven cases with benign mammograms had benign histology, and all 26 cases called "highly suggestive of malignancy" were malignant on histology (five C3 and 21 C4). Of the 23 cases called "suspicious abnormality" on mammography, 14 turned out to be malignant on biopsy (one C3 and 13 C4)., Conclusion: Our study supports maintaining cytology categories C3 and C4. About two-thirds of C3 cases were benign on biopsy whereas 81 percent of C4 cases were malignant (p-value is less than 0.001). There was complete correlation between histological and mammographical studies except those with equivocal mammograms. Our study supports the combined use of clinical, mammographical and cytological findings for optimal patient management. This is especially important for patients with C3 aspiration results, in order to avoid unnecessary surgery for benign lesions.

A number of genetic and epigenetic changes underlying the development of nasopharyngeal carcinomas have recently been identified. However, there is still limited information on the nature of the genes and gene products whose aberrant expression and activity promote the malignant conversion of nasopharyngeal epithelium. Here, we have performed a genome-wide transcriptome analysis by probing cDNA microarrays with fluorescent-labeled amplified RNA derived from laser capture microdissected cells procured from normal nasopharyngeal epithelium and areas of metaplasia-dysplasia and carcinoma from EBV-associated nasopharyngeal carcinomas. This approach enabled the identification of genes differentially expressed in each cell population, as well as numerous genes whose expression can help explain the aggressive clinical nature of this tumor type. For example, genes indicating cell cycle aberrations (cyclin D2, cyclin B1, activator of S-phase kinase, and the cell cycle checkpoint kinase, CHK1) and invasive-metastatic potential (matrix metalloproteinase 11, v-Ral, and integrin beta(4)) were highly expressed in tumor cells. In contrast, genes underexpressed in tumors included genes involved in apoptosis (B-cell CLL/lymphoma 6, secretory leukocyte protease inhibitor, and calpastatin), cell structure (keratin 7 and carcinoembryonic antigen-related cell adhesion molecule 6), and putative tumor suppressor genes (H-Ras-like suppressor 3, retinoic acid receptor responder 1, and growth arrested specific 8) among others. Gene expression patterns also suggested alterations in the Wnt/beta-catenin and transforming growth factor beta pathways in nasopharyngeal carcinoma. Thus, expression profiles indicate that aberrant expression of growth, survival, and invasion-promoting genes may contribute to the molecular pathogenesis of nasopharyngeal carcinoma. Ultimately, this approach may facilitate the identification of clinical useful markers of disease progression and novel potential therapeutic targets for nasopharyngeal carcinoma.

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.

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.

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis and meningoencephalitis. Almost all cases are self-limiting and are diagnosed by cerebrospinal fluid eosinophilia and enzyme-linked immunosorbent assay; pathology reports are restricted to postmortem samples from lethal cases. We report on what we believe is the first case of A. cantonensis infection diagnosed by biopsy in a living patient. The spinal cord was biopsied because of the unusual clinical presentation of a myelopathy without meningeal symptoms, together with a mass lesion that was clinically and radiologically diagnosed as a spinal cord tumor.

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., (Copyright 2002 Wiley-Liss, Inc.)

A common presentation of breast cancer is a palpable or non-palpable breast mass that might or might not demonstrate clinical signs of skin and/or nipple involvement. These malignant lesions frequently receive correct diagnosis only by physical examination under modestly experienced observers. We, hereby, reported the case of a 66-year-old woman who presented with a rapidly growing skin lesion at the left breast for three months. A 3.6x3x2.5 cm reddish, shiny, rubbery, sessile mass was seen on the upper outer quadrant of her left breast. The cytologic and histologic features of the tumor were typical for infiltrating ductal carcinoma. This case demonstrated a very unusual clinical presentation of breast cancer. No similar clinical feature of such cancer was mentioned in the reviewed literature.

Intraosseous proliferative sparganosis is an extremely rare parasitic disease in which the larvae of incomplete differentiated sparganum proliferate in the human bone. We present the first case of intraosseous proliferative sparganosis arising in the long bone. The patient was a 51-year-old man who complained of a slow growing painful mass on his right leg. The radiographic findings showed an infiltrative osteolytic lesion with speckled calcification at the proximal tibia the clinical diagnosis of which favored chondrosarcoma. Incisional biopsy revealed an innumerable number of small globular shapes, whitish parasites. Histologically, the parasites were composed of a few layers of smooth muscle and several calcerous bodies that were enclosed within a single row of tegumental cells. The latter exhibited a wavy appearance and coated with microvilli. These morphologic findings confirmed the nature of these maldifferentiated larvae. The patient was treated by partial resection of the lesion. This should remind clinicians that parasitic infection of the bone can produce a tumor-like lesion.

We reported a rare case of a primary intraosseous glomus tumor in a 53-year-old woman who had a small lytic lesion in the distal phalanx of her left index finger. The radiologic appearance showed a well circumscribed osteolytic lesion without sclerotic rim. Histologic examination revealed solid nests or sheets of polygonal cells surrounding branching vasculatures consistent with a glomus tumor. Curettage resulted in complete removal of the tumor as well as pain alleviation. The patient was well without evidence of recurrent disease following an 18 month follow-up. Despite its rarity, intraosseous glomus tumor should be included in the differential diagnosis of bone lesions in which plain radiography showed a well circumscribed punch-out lesion without sclerotic rim especially those arising in the finger.

Fine needle aspiration (FNA) has become a major diagnostic triage for clinical management of patients with a thyroid mass. Diagnostic accuracy of this procedure can be evaluated by cyto-histologic correlation. Out of 1,761 fine needle aspirates of thyroid glands performed from January 1996 to December 1999, 230 satisfactory specimens contained respective histologic correlates. Using histologic diagnoses as the gold standard, the overall accuracy, sensitivity and specificity for cytologic diagnoses of thyroid neoplasm were 90.4 per cent, 85.7 per cent, and 92.5 per cent respectively. The positive predictive value for diagnosing thyroid neoplasm was 83.3 per cent while the negative predictive value was 93.7 per cent. The common pairs of cyto-histological diagnostic discrepancy included adenomatous goiter vs follicular neoplasm, adenomatous goiter vs papillary carcinoma, and thyroiditis vs follicular neoplasm. In conclusion, FNA is a rapid, reliable and safe diagnostic tool to distinguish non-neoplastic from neoplastic lesions in patients with thyroid masses.

Adrenal myelolipoma is a rare nonfunctioning tumor consisting histologically of an admixture of adipose tissue and extramedullary hemopoietic elements within the adrenal glands. Less than 300 cases have been reported in the literature and only 15 case reports have described cytological findings of this tumor obtained by fine-needle aspiration (FNA). We report a case of a 48-year-old male who had had anaplastic large cell carcinoma of the right lung. The left adrenal mass was encountered during a staging workup that led to a clinical suspicion of metastatic disease to the adrenal gland. FNA under computed tomography (CT) guidance was performed obtaining cytological material from which diagnosis of myelolipoma was made. The findings reemphasized an important role of FNA in investigation of adrenal mass. The literature on FNA cytology of adrenal myelolipoma is reviewed. Diagn. Cytopathol. 1999;21:409-412., (Copyright 1999 Wiley-Liss, Inc.)

An 8-year prospective study of a cohort of 176 newly diagnosed leprosy patients was conducted to examine the possible influence of age, sex, multidrug therapy (MDT), and duration of illness on the risk of either type 1 or type 2 reactions. Patients were enrolled over a 5-year period (1984-1989) and followed for a minimum of 3 years. All reactions studied were severe enough to warrant hospital admission. Overall, 45% of this cohort developed a reaction; 32% of patients considered at risk developed type 1 reactions, and 37% of patients considered at risk developed type 2 reactions. Despite the predominance of men among the leprosy patients, type 1 reactions occurred with significantly greater frequency in women, and did not appear to be influenced by age of onset of leprosy. Individuals experiencing one type 1 reaction were not likely to experience a recurrence, suggesting that the immunologic mechanisms of this reaction may be limited or regulated by genetic or immunologic factors. Type 2 reactions, on the other hand, occurred with equal frequency in both males and females, but were highly associated with onset of leprosy in the second decade of life. Individuals who experienced type 2 reactions often had one or more recurrence of the reaction. No increased risk was seen for either reaction with longer duration of leprosy or longer duration of treatment. The mechanisms by which these differences relate to the pathogenesis of leprosy reactions remains unclear, but future studies of clinical and immunological parameters of leprosy reactions may benefit from stratification of data by gender and age of onset of leprosy in addition to the routine grouping of results by leprosy classification.

Prolonged expression of activated ras mutants resulted in both neoplastic transformation and suppression of serum-induced c-fos expression in Rat1 fibroblasts. Expression of other serum-inducible genes, including c-jun and beta-actin, was not suppressed in ras-transformed Rat1 cells, indicating that these effects are specific for c-fos and that growth-factor signal transduction pathways remain essentially intact. Run-on transcription studies indicated that c-fos transcription was blocked at the level of initiation in these cells. Transient transfection studies using 360 bp from the wild-type c-fos promoter as well as a series of mutated c-fos promoter fragments linked to the chloramphenicol acetyltransferase gene indicated that repression of c-fos was mediated by approximately 49 bp immediately upstream of the dyad symmetry element (DSE). Deletion of this region, referred to as the upstream repressor region (URR), restored serum inducibility to the c-fos promoter in ras-transformed cells. In contrast, suppression of c-fos transcription was not affected by either deletion of 240 bp between the DSE and the TATA element or by base-substitution mutations that inactive the ternary complex factor and fos-AP-1-like binding sites. In addition, in vitro competition studies indicated that ras-transformed cells express one or more repressor factors that interact with as-yet-unidentified elements within the c-fos promoter (possibly the URR) and block serum induction of c-fos. These findings suggest that prolonged expression of activated ras results in the activation of one or more as-yet-unidentified proteins that suppress transcription of the c-fos gene by interacting with the URR.

We report a case of paragonimiasis in a Nigerian woman evaluated for symptoms of chronic respiratory disease five years after chemotherapy for primary lymphoma of the breast. Fine needle aspiration of one of two fibrocavitary pulmonary lesions yielded thick, brown material in which ova diagnostic of Paragonimus westermani were identified cytologically. This disease is unusual in natives of North America but is seen in travelers and immigrants from Asia, Africa, and South and Central America, where it is endemic. The infection can be fatal, especially if it involves the central nervous system. The clinical differential is broad, but an accurate diagnosis may be made by fine needle aspiration, thus allowing proper treatment.

Muscle-specific actin (MSA) and desmin are considered to be sensitive and specific markers for muscle differentiation. The authors compared staining patterns for these markers in 576 samples of normal, reactive, and neoplastic tissues. The standard avidin-biotin-peroxidase complex technique was performed with the use of two commercial antibodies against MSA (HHF35; Enzo Biochemical, Inc., New York, NY) and desmin (DER11; DAKO Corporation, Santa Barbara, CA), respectively, on consecutive paraffin-embedded tissue sections from these cases. Both MSA and desmin were found in all 80 normal muscle samples. Although MSA appeared diffusely in all vascular smooth muscle samples, desmin was demonstrated focally in vascular smooth muscle cells in 100 of 196 samples. MSA but not desmin always was found in myoepithelial cells (25 samples), pericytes (286 samples), and decidual cells (7 samples). Among 76 cases of myofibroblast-containing lesions, 14 and 54 were found to have desmin and MSA, respectively. MSA and desmin were found in 4 of 4 cardiac rhabdomyomas, 34 of 34 rhabdomyosarcomas, and 5 of 6 leiomyomas. Among 22 leiomyosarcomas, 7 displayed either MSA or desmin and 7 showed both markers. In general, more tumor cells showed staining for MSA than desmin, but the reverse was true in some cases. Tissue fixed in Zenker's solution seemed to show a significant decrease in MSA immunoreactivity, but no significant change for desmin staining was observed. None of the 154 normal tissues and 22 benign nonmyogenic tumors expressed MSA or desmin. Among 133 malignant nonmyogenic tumors, positive staining for both desmin and MSA was found in 3 of 8 cases of glioblastoma multiforme, 1 of 10 malignant schwannomas, and 1 of 14 malignant fibrous histiocytomas; staining for only MSA was found in 3 of 14 malignant fibrous histiocytomas, 1 of 10 malignant schwannomas, 6 of 6 fibromatoses, 1 of 1 mammary myofibroblastoma, and 1 of 7 malignant mesotheliomas; and staining for desmin only was seen in 1 of 7 malignant mesotheliomas.(ABSTRACT TRUNCATED AT 400 WORDS)

The diagnostic utility of several antibodies against desmin and their optimal staining conditions have not been systematically evaluated. Sections of paraffin-embedded tissues from 584 cases were stained with a monoclonal antibody against desmin (Clone DER 11 from DAKO), using an avidin-biotin-peroxidase technique. The results were tabulated and compared with those from previous reports. The following observations were made: (1) When pronase digestion was performed before staining, desmin was equally demonstrable in tissues fixed in formalin, Zenker's, Bouin's, or B5 fixative; however, desmin staining was lost or significantly diminished in tissues fixed in absolute ethyl alcohol. In contrast, when pronase was not used, a positive staining was demonstrated only in tissue fixed in absolute ethyl alcohol. (2) Positive staining was found in normal muscle (92 of 92 cases), leiomyoma (12 of 13), rhabdomyoma (6 of 6), rhabdomyosarcoma (31 of 31), leiomyosarcoma (18 of 26). (3) Desmin was never found in epithelia, normal mesenchymal tissue other than muscle, tumors stimulating rhabdomyosarcoma, and epithelial tumors. (4) A positive staining was documented in 1 tumor (a fibrous histiocytoma) of 42 benign predominantly spindle cell tumors and in 8 of 89 predominantly spindle cell sarcomas. (5) Desmin was never documented in myoepithelial cells but stained myofibroblasts in 2 of 12 examples of granulation tissue and in 29 of 67 samples containing tumor-associated desmoplasia. The authors' data on the diagnostic sensitivity and specificity of the evaluated antibody should improve the use of desmin in diagnostic pathology.

A method is described using tuberculin purified protein derivative (PPD) as a model to follow the in vivo cellular immune response. This combines induction of a local response, formation of skin blisters, and staining of the cells appearing in the sterile exudate over time, using standard cytopreparatory and immunoperoxidase techniques. Skin blisters were induced over sites previously injected intradermally with PPD or control saline using suction over a template on the forearm. The cells which appeared in the exudate at 24, 36, 48 and 72 h were collected on small cellulose filters which were divided into several parts. The cells on the filter segments were then stained using a biotin-avidin immunoperoxidase method with a panel of monoclonal antibodies, and with enzyme histochemical techniques. This allowed quantitative estimation over an extended period of total numbers of each cell type responding as a local expression of cellular immunity. The kinetics of an early, non-specific inflammatory response could be distinguished from the later immune response using total cell counts. Maximal cell counts correlated well with PPD induced induration at 48 h, showing an overwhelming predominance of mononuclear cells. Over 72 h, the number of non-specific esterase (NSE) positive cells (macrophage) declined while Leu4 positive cells (T cells) increased. OKT4 positive cells (T helper) outnumbered OKT8 positive cells (T suppressor) as the response developed. This method enables the direct quantitative assessment of cell populations arriving at the site of an immune response using a simple inexpensive technique which is painless, non-invasive and non-scarring.

A rare cystic lesion of the pancreas is reported. Morphologically, this unilocular cyst was filled with keratin material and lined by mature, keratinizing squamous epithelium; it was surrounded by lymphoid tissue and also focally by pancreatic tissue. Clinically, the lesion was associated with diarrhea and abdominal pain, both of which promptly disappeared after its removal. Although the histogenesis of this lesion is not known, it can be histologically differentiated from other pancreatic and retroperitoneal cysts. We propose the name "lymphoepithelial cyst" for this lesion and note that only one similar case has been described previously.

The cellular contents of blisters induced by suction over new, uncomplicated leprosy lesions, and in the skin of cured, control patients, have been examined with enzyme- and immuno-histochemical staining over a period of 4 days. The total cellularity of the blisters varied over a wide range, not correlated with the type of leprosy. Mononuclear cells predominated at all times studied, with nearly equal percentages of monocytes and T lymphocytes. The T-helper: suppressor ratio was significantly greater in BT than in BL and LL lesions at 48 hr. Suction blisters offer a painless, quantitative, reproducible, multiple-sampling method for obtaining cells from the cutaneous infiltrates of leprosy for phenotyping or functional analysis.