Estrogen Receptor Expression in DICER1-related Lesions is Associated With the Presence of Cystic Components.

DICER1 tumor predisposition syndrome results from pathogenic variants in DICER1 and is associated with a variety of benign and malignant lesions, typically involving kidney, lung, and female reproductive system. Over 70% of sarcomas in DICER1 tumor predisposition syndrome occur in females. Notably, pediatric cystic nephroma (pCN), a classic DICER1 tumor predisposition syndrome lesion, shows estrogen receptor (ER) expression in stromal cells. There are also renal, hepatic, and pancreatic lesions unassociated with DICER1 tumor predisposition syndrome that have an adult female predominance and are characterized/defined by ER-positive stromal cells. Except for pCN, the expression of ER in DICER1-associated lesions remains uninvestigated. In the present study, ER expression was assessed by immunohistochemistry in 89 cases of DICER1-related lesions and 44 lesions lacking DICER1 pathogenic variants. Expression was seen in stromal cells in pCN and pleuropulmonary blastoma (PPB) types I and Ir, whereas anaplastic sarcoma of kidney and PPB types II and III were typically negative, as were other solid tumors of non-Müllerian origin. ER expression was unrelated to the sex or age of the patient. Expression of ER showed an inverse relationship to preferentially expressed antigen in melanoma (PRAME) expression; as lesions progressed from cystic to solid (pCN/anaplastic sarcoma of kidney, and PPB types I to III), ER expression was lost and (PRAME) expression increased. Thus, in DICER1 tumor predisposition syndrome, there is no evidence that non-Müllerian tumors are hormonally driven and antiestrogen therapy is not predicted to be beneficial. Lesions not associated with DICER1 pathogenic variants also showed ER-positive stromal cells, including cystic pulmonary airway malformations, cystic renal dysplasia, and simple renal cysts in adult kidneys. ER expression in stromal cells is not a feature of DICER1 perturbation but rather is related to the presence of cystic components.

Pediatric fibromyxoid tumor with PLAG1 fusion: An emerging entity with a novel intracranial location.

Translocations involving PLAG1 occur in several tumors, most commonly pleomorphic adenoma and lipoblastoma. Recently, a distinctive soft tissue tumor with a PLAG1 fusion has been reported in the pediatric age group. These are low grade tumors with a fibroblastic or mixed fibroblastic and myxoid morphology but no other lines of differentiation. They are typically immunopositive for desmin and CD34. The partner genes for these tumors have included YWHAZ, EEF1A1, ZFHX4l, CHCHD7, and PCMTD1. We report another case of this fibromyxoid tumor with a PLAG1 fusion, this time with COL3A1 as the partner gene. The fusion placed expression of a full-length PLAG1 protein under the control of the constitutively active COL3A1 promoter. Overexpression of PLAG1 was confirmed by diffusely positive immunostaining for PLAG1. The most novel aspect of this tumor is the intracranial location. Opinion has been divided over whether these tumors are a specific entity, or related to lipoblastoma, since that tumor also typically occurs in soft tissue in the pediatric age group and shows many of the same gene fusions. However, lipoblastoma has never been reported in an intracranial location and, thus, our case provides compelling evidence that this fibromyxoid tumor is indeed a distinct entity.

Simplified Molecular Subtyping of Medulloblastoma for Reduced Cost and Improved Turnaround Time.

Molecular subtyping of medulloblastoma (MB) has become increasingly important for prognosis and management. Typically this involves detailed molecular genetic testing which may not be available in all centers. The purpose of the present study was to find a simplified approach to assign molecular subtypes of MB for routine use in centers with more limited resources. The molecular subtypes of MBs from 32 Thai patients, aged 0.5 to 35 years, were first determined by NanoString. These results were then compared with those obtained using a combination of limited immunohistochemistry (IHC) (ß-catenin, GAB-1, YAP-1, p75-NGFR, OTX2) and CTNNTB exon 3 mutation analysis. By NanoString assay, there were 6 MBs (19%) in the wingless (WNT) group, 8 (25%) in the sonic hedgehog (SHH) group, 7 (22%) in group 3, and 11 (34%) in group 4. Although ß-catenin immunostaining missed 4/6 WNT MBs, CTNNTB mutation analysis confirmed all WNT MB cases with amplifiable DNA. The IHC panel correctly assigned all the other molecular subtypes, except for 1 MB in group 4. Thus, our protocol was able to correctly categorized 31/32 cases or 97% of cases. Our study is the first to report molecular subtypes of MB in Southeast Asia. We found that molecular subgroups of MBs can be reliably assigned using a limited IHC panel of ß-catenin, GAB-1, YAP-1, p75-NGFR, OTX2, together with CTNNTB exon 3 mutation analysis. This simplified approach incurs lower cost and faster turnaround time compared with more elaborate molecular methodologies and should be beneficial to centers with reduced laboratory resources.

Tubulovillous Adenoma of Vagina With Both KRAS and APC Mutations: Case Report.

Adenomatous polyps of the vulva and vagina are extremely rare. We report a case of a 74-yr-old women with a tubulovillous adenoma occurring in the vagina, and a second one occurring later in the vulva. Tumor cells in both lesions were CK7, CK20, CDX-2, and showed intact mismatch-repair proteins. A G13D (c.38G>A, p.Gly13Asp) mutation in the KRAS gene was identified in both masses. As well, a novel frameshift truncating mutation (c.4320delA, p.Pro1441fsTer32) in the APC gene was detected only in the vaginal mass, ruling out the possibility that the vulvar mass was a local recurrence of the vaginal mass. This is the first identification of KRAS and APC gene mutations in adenomatous polyps involving the female lower genital tract.

False-Negative Rate of Papanicolaou Testing: A National Survey from the Thai Society of Cytology.

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.

Natural course of low risk neuroblastoma.

BACKGROUND: Neuroblastoma is characterized by heterogeneity of histology, biology, and clinical behavior. Most epidemiology studies are based on Western and Japanese populations; there are very few studies on neuroblastoma from Southeast Asia. PROCEDURE: Cases of Thai children with neuroblastoma were retrospectively reviewed to determine if the epidemiology of the disease differs from Western populations. Sixty-two cases were assembled from two pathology centers in Bangkok. Histologic prognostic category and MYCN copy number were determined. RESULTS: The median age at diagnosis was 2.9 years. Only 11% of cases presented at less than 1 year of age and 12% cases had low stage disease (1, 2, and 4S). The majority of tumors had unfavorable histology (48/62); this was at least partly due to the higher age at diagnosis for most patients. MYCN amplification was detected in 18/52 (35%) tumors, all in stage 3 or 4 tumors. We assigned patients to high, intermediate and low risk categories using the Children's Oncology Group risk stratification criteria. In contrast to Western studies, the majority of cases (50/59 or 85%) in our series had high risk disease. CONCLUSIONS: Since there is no evidence to date that the biology of neuroblastoma varies by geographic region, the paucity of low risk cases in our study may reflect spontaneous resolution/differentiation of tumors that are not clinically detected. Moreover, a delay in diagnosis of intermediate risk cases could result in higher tumor burden at the time of diagnosis, increasing the proportion of high risk cases observed.

Rosai-Dorfman disease and juvenile xanthogranuloma in a Thai boy: report of a case.

A 3-year-old Thai boy suffered from two histiocytoses, Rosai-Dorfman disease (RDD) and juvenile xanthogranuloma (JXG). The patient first presented with massive cervical lymphadenopathy at the age of one year. Biopsy revealed typical RDD; abnormally large CD68- and S-100 protein-positive histiocytes with occasional emperipolesis filled up the sinuses. Two years later, he developed polyuria and polydypsia. Skull film demonstrated osteolytic lesions at the occiput and left parietal region. Enlargement of the pituitary stalk was found on the magnetic resonance imaging. Despite the clinical impression of Langerhans cell histiocytosis, biopsy of the occipital lesion disclosed numerous large histiocytes with foamy cytoplasm. Several Touton giant cells with wreath-like arrangement of the nuclei were also observed. The abnormal cells expressed CD68 and factor XIIIa, but were non-reactive with S-100 protein and CD1a. Biopsy of the pituitary stalk was not performed According to the authors' literature search, this represents the first report of RDD and JXG affecting the same person.

Expression of neuronal nuclear antigen (NeuN) in epithelial neuroendocrine carcinoma.

Expression of neuronal nuclei (NeuN), a mouse-derived neuronal-specific monoclonal antibody, has been found in almost all neuronal cell types throughout the nervous system. The authors have demonstrated NeuN immunoreactivity in 56% of epithelial neuroendocrine carcinomas (ENEC) (19/34): 4 of 7 (57%) grade 1 ENECs (carcinoid), 4 of 5 (90%) grade 2 ENECs (atypical carcinoid), and 11 of 22 (50%) grade 3 ENECs (small and large cell neuroendocrine carcinoma). Of the NeuN-positive cases, the immunoreactivity was localized primarily in the cytoplasm in 11 cases and in the nucleus in the remaining. Even though NeuN is not a highly sensitive marker for solo use, it would be useful as an adjunct in the panel immunohisto- chemistry of cases with histologic features suspicious of neuroendocrine differentiation.

Epstein-Barr virus infection-associated smooth-muscle tumors in patients with AIDS.

BACKGROUND: The aim of our study is to describe the unusual clinical manifestations of smooth-muscle tumors (SMTs) in patients with acquired immunodeficiency virus (AIDS) and to demonstrate the association between Epstein-Barr virus (EBV) infection and SMTs. METHODS: Nine patients with AIDS and SMTs were characterized at Chulalongkorn Hospital (Bangkok, Thailand) from 2001 through 2003. Tumor tissues suitable for immunohistochemical analysis and in situ hybridization were assayed for SMTs and EBV, respectively. Plasma and serum samples were tested for EBV by real-time quantitative polymerase chain reaction and serologic analysis. RESULTS: The study included 8 adults and 1 child (3 males and 6 females). All patients had CD4 cell counts of <200 cells/microL. By the end of the study, 3 patients had died, and 6 patients had survived. The sites of SMTs were the epidura (5 intracranial and 4 intraspinal SMTs), vocal cords (2), adrenal glands (2), abdominal wall (2), iris (1), liver (1), lung (1), orbit (1), and thigh (1). Seven patients had multicentric SMTs involving intracranial sites only (4 SMTs), extra- and intracranial sites (3), or extracranial sites only (2), which occurred either concurrently or sequentially. We found evidence of EBV infection, as determined by in situ hybridization, in all SMTs. Furthermore, EBV DNA was detectable in plasma samples from 2 patients. The results of serologic analysis were consistent with past EBV infection. CONCLUSIONS: SMTs in patients with AIDS typically arise in multiple and very unusual sites that are not often observed in SMTs among immunocompetent individuals. Our series also suggests association between EBV infection and SMTs in patients with AIDS. The exact role of EBV in smooth-muscle oncogenesis awaits further study.

LacCur stain for detection of mucin in adenocarcinoma.

Identification of cytoplasmic mucin, usually by Mayer's mucicarmine stain, is one of the criteria to diagnose adenocarcinoma. The inexpensive LacCur stain, made up of Curcuma longa (khamin-shan) and secreta of Laccifer lacca (krang) has been introduced. The aim of this study was to compare the Mayer's mucicarmine and LacCur stains in the detection of mucin material. The specimens included 17 adenocarcinomas of the stomach, 16 of the colon, 18 of the lung, 16 of the breast, and 12 of the bile duct. Squamous cell carcinoma and hepatocellular carcinoma (altogether 20 cases) were set as negative control. Like Mayer's mucicarmine, LacCur was capable of detecting of intracytoplasmic mucin in all adenocarcinomas of the stomach, colon and bile duct, and revealed mucin substance in 15/18 and 11/16 cases of specimens from the lung and breast, respectively. The negative control group showed a negative result. Although a little more time required in preparation, the LacCur stain is simple and very economical.

Intra-operative diagnosis in surgical neuropathology: a study of 120 cases with reference to squash cytology.

OBJECTIVE: To present results of intra-operative consultation in surgical neuropathology and discuss the diagnostic guideline for squash cytology. MATERIAL AND METHOD: The intra-operative pathological diagnosis of 120 neurosurgical specimens was compared with the final histologic diagnosis. Squash preparation was used solely in 83 cases, frozen sections alone in 3 cases, and both techniques in the remaining. An algorithm for cytologic diagnosis was described. RESULTS: The intra-operative pathological diagnoses in neurosurgery were completely (83%) and partially (13%) correlated with the final results. CONCLUSIONS: Intra-operative diagnosis in surgical neuropathology is reliable. Squash cytology is highly recommended as an alternative approach.

Solitary mastocytoma of the vulva: report of a case.

A solitary mastocytoma was encountered involving the left labium majus of a 6-year-old girl. Tumor cells contained numerous cytoplasmic metachromatic granules that were immunoreactive for tryptase and CD117. As mast cells are difficult to recognize on routine stains, identification of mast cell lesions requires a high degree of suspicion. This is probably the first reported case of mastocytoma occurring in the vulva.