The cut-offs for kappa/lambda ratio in bone marrow immunohistochemistry for the diagnosis of multiple myeloma.

Objective: The previously reported kappa/lambda ratio cut-offs for plasma cell clonality by immunohistochemistry were in different values. This study aimed to identify the cut-offs with the highest accuracy for the diagnosis of multiple myeloma. Methods: Bone marrow specimens consecutively recruited between January 2011 and March 2019. The patients were at least 18 years old with clinical suspicion of multiple myeloma and had bone marrow plasma cell ≥10% by CD138 immunohistochemistry. The index test was immunohistochemical stains for plasma cell kappa/lambda ratio. The reference standard to classify as multiple myeloma required meeting any of the following (1) kappa/lambda ratio ≤1/16 or ≥16, (2) abnormal plasma cell morphology, and (3) monoclonal immunoglobulin. Results: From 147 specimens (70 multiple myelomas and 77 reactive plasmacytosis), our cut-offs kappa/lambda ratio for light chain restriction at ≤1/7 or ≥9 yielded an area under the receiver operating characteristic curve of 1.0000 while ≤1/16 or ≥16 yielded 0.9643 (p-value 0.0212). Conclusion: The cut-offs for kappa/lambda ratio at ≤1/7 or ≥9 for diagnosis of multiple myeloma yielded the highest diagnostic accuracy. The suggested cut-offs could be of potential value in resource-limited laboratories.

Female urinary retention from a huge periurethral mass caused by immunoglobulin G4-related disease (IgG4-RD).

Immunoglobulin G4-related disease is a systemic disease, recognized as extensive T-lymphocyte and IgG4-positive plasma cells. It can present as inflammatory pseudotumor in various organs. A female 75 years old, diagnosed IgG4-related autoimmune pancreatitis, presented with urinary retention. Pelvic examination showed well-defined, soft tissue mass, bulging from anterior vaginal wall. MRI pelvis demonstrated a huge periurethral mass, size 6.2 × 4.4 × 4.2 cm, encasing the urethra, extending from bladder neck to distal urethra, and mimicking the prostate gland. Tissue biopsy showed compatible with IgG4-related disease. Immunosuppresive drugs were given for few months and the patient could void normally.

Fetal and Placental Pathology in Congenital Syphilis: A Comprehensive Study in Perinatal Autopsy.

INTRODUCTION: At autopsy, without available serologic information, diagnosing congenital syphilis (CS) relies on identification of Treponema pallidum in tissues. Recognition of clues leading to detection of the organism is important. MATERIALS AND METHODS: Autopsy cases with CS were studied for fetal and placental abnormalities. RESULTS: Twenty-one cases were recruited: 12/21 with identifiable T. pallidum and 9/21 with positive serology and characteristics of CS. 20/21 (95%) demonstrated ≥1 fetal abnormalities. Chronic stress involution of thymus was most common. Hydrops and hepatosplenomegaly were found in >50%. Metaphyseal abnormalities and organ inflammation were found in <30%. Mucocutaneous lesions were lacking. Placental abnormalities were identified in 20/21 (95%). Placentomegaly was most common. Amniotic fluid infection (AFI) was noted in >50%. CONCLUSION: Common findings in CS at autopsy include chronic stress involution of thymus, hydrops, and hepatosplenomegaly. Mucocutaneous lesions are uncommon. Common placental findings in fetal deaths due to CS include placentomegaly and AFI.

Metastatic Melanoma of Uncertain Primary with 5-Year Durable Response after Conventional Therapy: A Case Report with Literature Review.

A 51-year-old Thai woman presented with bilateral leg edema and painful left inguinal mass for 6 months. Physical examination revealed matted bilateral inguinal lymph nodes up to 9 cm in size. Otherwise, physical examinations including skin were unremarkable. The result of the lymph node incisional biopsy is consistent with that of metastatic melanoma. The extensive investigation demonstrated multiple intra-abdominal and inguinal lymph nodes without detectable primary tumor. Palliative radiation and conventional chemotherapy were prescribed. The CT scan between treatments showed that the response was stable disease, but the following CT scan demonstrated a gradual decrease in size from August 2012 to November 2017 including the lesions outside radiation fields. Moreover, she developed vitiligo during a follow-up visit. The previous data reported the median overall survival among the patients who were treated with conventional chemotherapy ranging from 9.1 to 9.3 months and whose 5-year survival was less than 10%. This case represented a metastatic melanoma of unknown primary who achieved a durable response by conventional treatment. The clinical features including nodal-only disease, vitiligo, and abscopal effect of radiation were considered to be the favorable factors.

Hematologic Malignancies Associated With Mediastinal Germ Cell Tumors: 10 Years' Experience at Thailand's National Pediatric Tertiary Referral Center.

Mediastinal germ cell tumor (MGCT), which accounts for 1% to 3% of extragonadal germ cell tumors, has unique manifestations; it is associated with several types of hematologic malignancy, particularly myeloid neoplasm. The aim of this study was to report the 10-year incidence, clinical characteristics, and outcomes of MGCT at Thailand's national pediatric tertiary referral center. This retrospective study included patients diagnosed with MGCT at the Department of Pediatrics, Siriraj Hospital during 2005 to 2014. Eight patients (all male) were diagnosed with MGCT. Five of 8 patients were found to have hematologic abnormalities. Three patients were diagnosed with acute myeloid leukemia (AML) (one patient with M1, another having M7, and the other with M0). Another patient had mixed MGCT with mediastinal myeloid sarcoma (MMS). The other patient had malignancy-associated hemophagocytic lymphohistiocytosis syndrome (M-HLH). Isochromosome 12p was detected in 3 patients (AML [2], mixed MGCT/MMS [1]). Four of 5 patients with hematologic abnormalities died of hematologic abnormalities or treatment complication (AML [3], M-HLH [1]). One patient with mixed MGCT/MMS survived with chemotherapy. All patients with AML and MMS were nonseminomatous MGCT and the onset of myeloid malignancies were within 1 year after the diagnosis of MGCT. Associated hematologic malignancies should be suspected in MGCT with abnormal blood count or hematologic symptoms. Isochromosome 12p was the most common cytogenetic finding in MGCT-associated myeloid malignancies patients. Those with nonseminomatous MGCT should have their blood count carefully monitored especially during the first year after the diagnosis of MGCT. Better treatment alternatives for MGCT with associated hematologic malignancies are warranted to ameliorate adverse outcomes.

Subcutaneous Panniculitis-Like T-Cell Lymphoma Versus Lupus Erythematosus Panniculitis: Distinction by Means of the Periadipocytic Cell Proliferation Index.

The distinction between subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus (LE) panniculitis is remarkably challenging. Rimming by lymphocytes with an elevated Ki-67 cell proliferation index has been forwarded as a potential diagnostic finding in biopsies of SPTCL but has not been rigorously compared with biopsies from patients with LE panniculitis. Nineteen and 17 examples of SPTCL and LE panniculitis, respectively, were evaluated for periadipocytic rimming by lymphocytes expressing Ki-67, CD8, and ßF1 and for attributes associated with LE, including clusters of CD123-positive cells. The identification of periadiopocytic rimming using Ki-67, CD8, and ßF1 held sensitivity of 79%, 100%, and 89.5% and specificity of 100%, 52.9%, and 88.2%, respectively (P < 0.01). CD123-positive cells were in both disorders. LE-like histopathology was commonly encountered in SPTCL. In conclusion, an elevated Ki-67 cell proliferation index with rimming is useful for distinguishing SPTCL from LE panniculitis. Notably, many features of LE panniculitis can also be encountered in SPTCL.

Discordant Anomalies with Combined Features of Pentalogy of Cantrell and OEIS Complex: A Case Report in Monochorionic Twins.

INTRODUCTION: Ventral body wall defects have various manifestations. Among others, pentalogy of Cantrell (PC) and omphalocele exstrophy imperforate anus spinal abnormalities (OEIS) complex are defects that involve upper and lower anterior midline of body wall, respectively. Although both entities are in a spectrum of ventral body wall defects, the combination of PC and OEIS complex has not been described. CASE REPORT: In this report, we describe an unusual case of congenital ventral body wall defect with combined features of PC and OEIS complex, which discordantly occurred in monochorionic monoamniotic twins. CONCLUSION: PC and OEIS complex may be related regarding their embryologic origins. The combination may represent the most severe manifestation of ventral body wall defects.

Immunoarchitectural patterns of progressive transformation of germinal centers with and without nodular lymphocyte-predominant Hodgkin lymphoma.

Progressive transformation of germinal centers (PTGC) has been frequently described in association with Hodgkin lymphoma, particularly nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). The aim of this study was to evaluate morphologic features of PTGC for better delineation of PTGC from early involvement by NLPHL. A total of 160 cases of PTGC were evaluated and included in the following 3 groups: 93 patients with PTGC who never developed a lymphoma, 23 patients with synchronous PTGC and NLPHL, and 44 patients with PTGC with antecedent or subsequent history of lymphoma. By histopathologic evaluation, 5 patterns of PTGC that reflected progressive dismantling of germinal centers were identified. There was no difference in the distribution of patterns 1 to 4 among the 3 groups of PTGC; however, in patients showing synchronous involvement of PTGC and NLPHL, pattern 5, which resembles a naïve B-cell follicle, was significantly more frequently observed (14/23) when compared with patients with PTGC who never developed a lymphoma (30/93; P = .0161). Furthermore, recognition of the spectrum of immunoarchitectural patterns of PTGC, including architectural and cytologic features, was helpful to better differentiate nodules involved by PTGC from NLPHL.

Large B-cell lymphoma with T-cell-rich background and nodules lacking follicular dendritic cell meshworks: description of an insufficiently recognized variant.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is characterized by nodular or nodular and diffuse growth of scattered large neoplastic B cells associated with follicular dendritic cell (FDC) meshworks. Variant patterns, which at least focally show a T-cell-rich background, and rare cases lacking FDC meshworks that overlap with T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) are also recognized. We reviewed 195 cases spanning the diagnostic spectrum of NLPHL and THRLBCL and identified 5 cases with distinctive features that were difficult to classify according to the World Health Organization criteria or previously described variants. Clinically, they involved peripheral and central lymph node sites or the mediastinum, and the majority also had recurrent disease. Four cases showed large T-cell-rich nodules with fibrosis, and 1 showed diffuse THRLBCL-like pattern with a minor component of nodularity. All cases completely lacked FDC meshworks despite a prominent nodular growth pattern. Large atypical cells in all cases were CD20+ CD30- CD15- B cells, although a small subset (<10%) of CD30+ and CD15+ large cells were seen in 1 case. In 4 cases, the background mainly contained CD4+ PD-1+ or CD57+ T cells that ringed large atypical B cells. In 1 case, B-cell predominance and a ringing pattern of CD57+ T cells were noted in nodules, whereas they were lacking in the diffuse areas. Recognition of these variant cases expands the spectrum between NLPHL and THRLBCL and points to the need for further refinement of diagnostic criteria for appropriate classification and clinical management.

Primary intrarenal/perirenal neuroblastoma mimicking Wilms' tumor at presentation in a 5-year-old girl: a case report from Siriraj hospital.

Primary intrarenal/perirenal neuroblastoma (NB) is NB that primarily arises in intrarenal and/or perirenal regions. Regarding its location, this tumor can mimic Wilms' tumor a more common pediatric renal tumor at presentation. Owing to diference in clinical management andprognosis, it is crucial to distinguish primary intrarenal/perirenal NB from Wilms' tumor at the time of diagnosis. Recognition of its characteristic features, which are distinctive from its adrenal counterpart, is helpful to guide to the correct diagnosis and proper treatment. However,; due to its rarity with less than 100 cases described in English literatures, the characteristics of primary intrarenal/perirenal NB have not been widely studied The authors, therefore, report this case of primary intrarenal/perirenal NB, which occurred in right kidney of a 5-year-old Thai girl in order to illustrate the characteristic features of this tumor To the authors'knowledge, this case is the first case ofprimary intrarenal/perirenal NB that has been reported in Thailand

Features of gastric and colonic mucosa in congenital enteropathies: a study in histology and immunohistochemistry.

Congenital enteropathies comprise a constellation of rare clinicopathologic diagnoses characterized by intractable watery diarrhea and failure to thrive in infants. These diagnoses include, but are not limited to, tufting enteropathy (TE), microvillous inclusion disease (MID), and enteroendocrine cell dysgenesis (EED). Commonly, the diagnosis is based on identification of their characteristic histologic and/or ultrastructural features in small intestinal mucosa. In cases in which the changes in the small intestine are inconclusive or a small intestine biopsy is not performed, the diagnosis can be hampered or significantly delayed. We describe the histologic features and immunohistochemical staining patterns of gastric and colonic mucosa in patients with confirmed TE (3), MID (2), and EED (1). Specifically, focal epithelial tufts were found in the gastric mucosa of one TE patient and multifocally in the colonic mucosa of another. All TE patients showed complete loss of membranous epithelial EpCAM expression in gastric and colonic mucosa, characteristic of the diagnosis. Gastric biopsies were available in 1 patient with MID; this showed focal disruption of the gastric glandular architecture. Three colon biopsies and 1 resection from 2 patients with MID showed characteristic cytoplasmic vacuoles and periodic acid-Schiff/villin-positive cytoplasmic inclusions. Chromogranin stains showed complete absence of enteroendocrine cells within the colon and a normal distribution in the gastric mucosa of the EED patient. On the basis of our findings, we conclude that the characteristic histologic and immunohistochemical features associated with the small intestine can be confirmed within the gastric and/or colonic mucosa by careful histologic examination and immunohistochemistry.

Variable expression of B-cell transcription factors in reactive immunoblastic proliferations: a potential mimic of classical Hodgkin lymphoma.

Reactive immunoblastic proliferations can histologically mimic classical Hodgkin lymphoma (CHL), and show diffuse CD30 expression in large cells. The lack of expression of CD15 in a subset of CHL further complicates their separation from immunoblastic proliferations. Loss of expression of B-cell transcription factors is frequently exploited in making a diagnosis of CHL; however, the staining patterns of B-cell transcription factors in immunoblastic proliferations have not been extensively studied. Thirty-three cases of reactive immunoblastic proliferations were evaluated using a panel of immunohistochemistry for CD30, CD15, CD20, CD3, κ, λ, CD45RB, MUM1, PAX5, OCT2, and BOB.1, as well as Epstein-Barr virus (EBV)/EBV-encoded ribonucleic acid in situ hybridization. A newly developed dual-color chromogenic in situ hybridization technology for detection of κ/λ mRNAs was also used. The majority of immunoblasts expressed CD30 in 14 of 33 (42%) cases; none expressed CD15. Loss or weak expression of at least 1 transcription factor in B immunoblasts, most commonly PAX5, was noted in 24 of 29 (83%) cases. A polytypic light chain expression pattern was detected by immunohistochemistry in 14 of 22 (63.6%) cases and by dual-color chromogenic in situ hybridization in 9 of 10 (90%) cases studied. EBV-encoded ribonucleic acid was detected in 8 of 33 (24.2%) cases, 5 of which were clinically unrelated to infectious mononucleosis. We conclude that B-cell transcription factors can show loss or weak expression in a significant proportion of reactive immunoblastic proliferations, and, therefore, staining for B-cell transcription factors together with CD30 should be interpreted with caution before a diagnosis of CHL is made.

Plasma cell neoplasms presenting with masses: a study on morphology, expression of CD56 and cyclin D1, and presence of Epstein-Barr virus in 39 Thai patients in SiriraJ Hospital.

BACKGROUND: Plasma cell neoplasms (PCNs) presenting with masses are not common. Variable morphology, expression of CD56 and cyclin D1, and Epstein-Barr virus (EBV)-encoded small RNA (EBER) status have been described with a promising diagnostic role. There is no data of these findings in Thai patients. OBJECTIVE: To study morphology, CD56 and cyclin D1 expression and EBER status in PCNs presenting with masses. MATERIAL AND METHOD: Thirty-nine mass-forming PCNs with available materials between 2006 and 2010 were identified from Siriraj Hospital pathology database. H&E slides were reviewed for morphologic grade according to Bartl grading system. Immunohistochemistryfor CD56 and cyclin D1 and EBER in situ hybridization were analyzed on tissue microarray sections of the included cases. RESULTS: Of 39 cases, it comprised 31 (79.5%) plasma cell myelomas (PCMs), five (12.8%) osseous plasmacytomas (OPs), and three (7.7%) extramedullary plasmacytomas (EMPs). Intermediate-grade morphology was common to all types of PCNs. CD56 and cyclin D1 positivity were more often in PCMs comparing with OPs and EMPs; however differences in expression of these markers among different types of PCNs were insignificant (p > 0.05). An EBER-positive EMP was identified. CONCLUSION: The majority of mass-forming plasma cell tumors in the studied population are PCM-related. Intermediate-grade morphology is common in all types of PCNs. A value of CD56 and cyclin D1 immunostains in discrimination between types of PCNs cannot be confirmed in the current study. Identification of the EBER-positive EMP suggests that EBV association in plasma cell tumor can be encountered in Thais.

A 13-year-old female with Xp11.2 translocation renal cell carcinoma; the first case diagnosed at Siriraj Hospital.

Xp11.2 translocation renal cell carcinomas are rare tumors characterized by translocations involving chromosome Xp11.2. These tumors are predominantly reported in pediatric patients. The authors report Xp11.2 translocation renal cell carcinoma in a 13-year-old girl who presented with asymptomatic palpable right renal mass. Right radical nephrectomy was performed and revealed a well-defined solid mass at the lower pole of the kidney. Microscopically, the tumor was composed of sheets and nests of clear to pale eosinophilic cells with some alveolar growth pattern. Psammoma bodies were detected. Immunohistochemically, the tumor cells marked with TFE3, focally marked with smooth muscle actin, HMB-45, CD68, progesterone receptor (PR) and CD10 but did not mark with epithelial markers (AE1/AE3, EMA and CAM5.2), vimentin, S-100 and p53. The presence of psammoma bodies is an important diagnostic clue for these tumors. Cytogenetic study and/or immunohistochemistry for TFE3 protein are needed for confirming the diagnosis. Currently, surgery seems to be the most effective therapy Pediatric patients with these tumors are believed to have a favorable prognosis.

Teratoid Wilms' tumor: case report of a rare variant that can mimic aggressive biology during chemotherapy.

Teratoid Wilms' tumor is considered by some as a variant of Wilms' tumor containing at least 50% heterologous differentiated tissue. Fewer than 30 cases have been described. We report a 9-month-old boy with bilateral Wilms' tumors who did not respond to multiagent chemotherapy and underwent right nephrectomy that showed a teratoid Wilms' tumor. The patient continued to survive despite cessation of treatment. The overall predominance of differentiated stromal elements in this subtype of Wilms' tumor might explain the poor response to chemotherapy yet generally favorable outcome. Recognition of this subtype on biopsy might justify earlier surgical intervention that, for bilateral tumors, might allow for greater nephron sparing.

Combination of cor triatriatum sinistrum and hypoplastic left heart syndrome in Meckel-Gruber syndrome: a case report.

Meckel-Gruber syndrome (MKS) is a fatal, autosomal recessive disorder characterized by malformation of central nervous system, particularly occipital encephalocele, bilateral renal dysplasia, and polydactyly. However, the clinical findings of this syndrome encompass various organ abnormalities as a result of genetic heterogeneity. The associated heart anomaly in MKS is inconstant. Its prevalence is rare and no striking or specific cardiac defects have been documented. We present a case of MKS with combined cor triatriatum sinistrum (left atrium divided into upper and lower compartment by a thin membrane) and hypoplastic left heart syndrome (underdeveloped mitral valve, left ventricle, and aorta) in a 33-week male fetus that was ultrasonographically detected and confirmed by autopsy. In addition to the cardiac defects, the patient was found to have postaxial polydactyly of 4 extremities, Dandy-Walker malformation, bilateral renal cystic dysplasia, and hepatic plate malformation. To the best of our knowledge, this is the first time that a combination of cor triatriatum sinistrum and hypoplastic left heart syndrome in MKS has been reported in the literature.

Mixed embryonal/alveolar rhabdomyosarcoma of the prostate: report of a case with molecular genetic studies and literature review.

Alveolar rhabdomyosarcoma (RMS) is 1 of 2 main subtypes of RMS in the pediatric age group and tends to occur in the extremities. The urogenital tract is another common site for RMS, but this typically involves the embryonal subtype including sarcoma botryoides. We report a 28-year-old male with a prostatic tumor that was excised en bloc and showed a RMS with separate areas of embryonal and solid alveolar morphologies at the light microscopic level. Both areas showed diffuse nuclear expression for myogenin, and both areas expressed the PAX3-FKHR fusion gene, a genetic change associated with alveolar but not embryonal RMS. A review of the literature documented only 5 cases of RMS primary to the prostate showing alveolar or mixed histology. Ours is the 6th case and the 1st with molecular findings. Although the diagnostic category of mixed embryonal/alveolar RMS remains in use, the nature of this type of RMS is incompletely understood. In our case, although the morphology was mixed embryonal/alveolar, at the genetic level this tumor was alveolar in nature.