Madhu Rajeshwari

Biphenotypic sinonasal sarcoma: A series of six cases with evaluation of role of β-catenin immunohistochemistry in differential diagnosis

INTRODUCTION Biphenotypic sinonasal sarcoma (BSNS) is a recently described mesenchymal tumor exclusive to the sinonasal region. It is a low grade sarcoma, displaying evidence of myogenic and neural differentiation. Role of β-catenin immunohistochemistry in distinguishing it from its morphological mimics is not well-established. We conducted this study to identify cases of BSNS from our archives, and to examine immunopositivity for β-catenin in them as well as in its close differential diagnosis. METHODS All cases of nasal cavity and paranasal sinus mesenchymal neoplasms were identified. Histopathological features were reviewed. Cases showing smooth muscle actin (SMA) and S-100 immunopositivity, and typical morphology were reclassified as BSNS. β-catenin immunoexpression was assessed. RESULTS Twenty-one mesenchymal tumors, including 12 sinonasal hemangiopericytoma (SNHPC), five solitary fibrous tumors (SFT), three BSNS, and one synovial sarcoma were identified. Three SNHPC cases were reclassified as BSNS. BSNS patients included one male and five females, with mean age of 51years. Five BSNS cases (83.3%) showed nuclear β-catenin immunopositivity. SNHPC cases also were β-catenin positive (60%). CONCLUSION BSNS is a rare sinonasal neoplasm, frequently misdiagnosed as SNHPC and SFT. β-catenin immunopositivity is seen in majority of cases, indicating a role in pathogenesis. However, due to positivity in other tumors like SNHPC, it has limited role in differential diagnosis.

WNT-activated medulloblastoma with melanotic and myogenic differentiation: Report of a rare case.

Medulloblastoma (MB) with melanotic and myogenic differentiation, previously known as melanotic medullomyoblastoma, is an extremely rare histological variant of MB showing melanocytic as well as skeletal muscle differentiation. Only 10 cases of this rare tumor have been reported in the literature to date. We report this case of a 2‐year‐old male child who presented with a midline cerebellar mass, which on histopathological examination showed classic MB intermixed with cells containing melanin pigment, along with rhabdomyoblasts, spindle cells and occasional strap cells, which corresponded to WNT subgroup on molecular classification. The cell of origin of this MB variant is likely to be neural crest‐derived stem cells which are capable of multilineage differentiation. Significant findings from previous reports and important differential diagnoses are discussed. Documentation of these tumors is important to characterize the clinical behaviour and to identify distinct genetic features, if any.

A Comparative Immunohistochemical Study of Epithelial Membrane Antigen and NHERF1/EBP50 in the Diagnosis of Ependymomas.

Ependymomas are gliomas that recapitulate normal ependymal cells. The epithelial membrane antigen (EMA) shows “dot-like” and “ring-like” staining patterns, highlighting “microlumens” or intracytoplasmic rosettes, a pathognomonic ultrastructural feature. NHERF1/EBP50, an adaptor protein localized at the apical plasma membrane of human epithelia, has been found to localize to these microlumens. We aimed to analyze the staining patterns of EMA and EBP50 in ependymomas and other tumors, and thereby compare their diagnostic utility. Sixty-three ependymomas of different grades and 44 nonependymal tumors (meningiomas, 5; pilocytic astrocytoma, 2; paraganglioma, 2; neurocytoma, 4; pituitary adenoma, 3; papillary tumor of pineal region, 3; oligodendroglioma, 4; choroid plexus papilloma, 3; medulloblastoma, 2; schwannoma, 2; cellular hemangioblastoma, 2; subependymal giant cell astrocytoma, 1; glioblastoma multiforme, 8; diffuse astrocytoma, 1; anaplastic astrocytoma, 1; and pilomyxoid astrocytoma, 1) were included. Ring-like positivity was 100% specific for ependymomas, but showed a poor sensitivity (EMA, 29%; EBP50, 37%). Dot EMA positivity was more sensitive in grade III ependymomas (100%), whereas dot EBP50 positivity was more sensitive in grade I subependymomas (80%) and myxopapillary ependymomas (40%). Among grade II ependymomas, EBP50 labeled a significantly higher number of dots and rings, which may be of value in small biopsies. Focal dot positivity for EMA and EBP50 in glioblastoma multiforme and meningioma contributed to the lowered specificity (EMA, 84%; EBP50, 80%). Myxopapillary ependymomas (60%), choroid plexus papillomas (66%), and papillary tumors of pineal region (100%) showed membranous staining with EBP50. Although EPB50 appears to be a better diagnostic marker for grade I/II ependymomas, we recommend a combined panel of EMA and EBP50 for grade III ependymomas to compensate for the reduced sensitivity of EBP50 in this subgroup.

Childhood macrophagic myofasciitis: A series from the Indian subcontinent

Macrophagic myofasciitis (MMF) is a rare disorder, reported mainly in European adults, with occasional childhood cases. We report a series of 6 patients with pediatric MMF from the Indian subcontinent.

Acid-Fastness of Histoplasma in Surgical Pathology Practice

Background Histoplasmosis (HP) is diagnosed by visualizing intracellular microorganisms in biopsy and/or culture. Periodic-acid Schiff (PAS) and Gomori methenamine silver (GMS) staining methods are routinely used for identification. The acid-fast property of Histoplasma was identified decades ago, but acid-fast staining has not been practiced in current surgical pathology. Awareness of the acid-fast property of Histoplasma, which is due to mycolic acid in the cell wall, is important in distinguishing Histoplasma from other infective microorganisms. Here, we examined acid-fastness in previously diagnosed cases of Histoplasma using the Ziehl-Neelsen (ZN) stain and correlated those findings with other known fungal stains. Methods All cases diagnosed as HP were retrieved and reviewed along with ZN staining and other fungal stains. We also stained cases diagnosed with Cryptococcus and Leishmania as controls for comparison. Results A total of 54 patients ranging in age from 11 to 69 years were examined. The most common sites of infection were the skin, adrenal tissue, and respiratory tract. Of the total 43 tissue samples, 20 (46.5%) stained positive with the ZN stain. In viable cases, a significant proportion of microorganisms were positive while necrotic cases showed only rare ZN-positive yeasts. In comparison to PAS and GMS stains, there was a low burden of ZN-positive yeasts. Cryptococcus showed characteristic ZN staining and all cases of Leishmania were negative. Conclusions Although the morphology of fungal organisms is the foundation of identification, surgical pathologists should be aware of the acid-fast property of fungi, particularly when there is the potential for confusion with other infective organisms.

A case of primary spinal atypical teratoid/rhabdoid tumor in a 5-year-old child

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare central nervous system neoplasm affecting children, and isolated primary spinal involvement is extremely rare. Authors describe a case of spinal AT/RT in a 5-year-old male child presenting with rapidly progressing quadriparesis diagnosed and managed surgically and medically. Biopsy revealed large, rhabdoid cells with prominent nucleoli in nest and immunohistochemistry further showed loss of integrase integrator 1 expression considered to be gold standard for diagnosis. AT/RT has extremely poor prognosis with median survival being 6 months.

Primary diffuse large B-cell lymphoma of the prostate: A report of two cases with diagnostic considerations

Primary prostatic lymphomas are extremely unusual neoplasms. Their rarity and nonspecific symptomatology at presentation usually prompt a clinical diagnosis of benign prostatic hyperplasia or chronic prostatitis, leading to significant delay in diagnosis. Clinical examination, serum prostate-specific antigen levels, and transrectal ultrasonography (TRUS) are not of much utility in differential diagnosis, and histological examination is the gold standard. We report two cases of primary non-Hodgkin lymphoma of prostate, diffuse large B-cell type, diagnosed on TRUS-guided prostatic biopsies. Correct diagnosis is of crucial importance as the therapeutic strategy for lymphoma is radically different from that for carcinoma, and early detection of prostatic lymphoma can be potentially curative. Thus, knowledge of this rare entity, inclusion in differential diagnosis of lower urinary tract obstruction, and application of an appropriate immunohistochemical panel are essential so as not to miss this unusual diagnosis and to avoid unnecessary surgery.

Epithelial-to-mesenchymal transition related transcription factors are upregulated in ependymomas and correlate with a poor prognosis

Epithelial-to-mesenchymal transition (EMT) plays an important role in invasion and metastasis of various cancers including gliomas. EMT has also been linked to cancer stem cells and resistance to chemotherapy. An initial in-silico data mining in a published ependymoma (EPN) patient series (GSE21687) revealed up-regulation of EMT transcription factors in tumor samples. Furthermore, quantitative real-time polymerase chain reaction-based gene expression analysis of EMT transcription factors in 96 EPNs showed significant up-regulation of SNAI1, SNAI2, ZEB1, and TWIST1 as compared with normal brain, associated with up-regulation of CDH2/N-cadherin and down-regulation of CDH1/E-cadherin. Although this was observed in varying degrees in all clinicopathological-molecular subgroups of EPNs, it was most evident in supratentorial EPNs harboring fusions of RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) gene and in posterior fossa EPNs. Immunohistochemistry performed in 60 of the above cases corroborated with gene expression patterns, and immunopositivity for Snail, Slug, Zeb1, and Twist1 was observed in 80%, 80%, 81%, and 63% of all EPNs. Immunopositivity for N-cadherin and E-cadherin was observed in 76.6% and 2% of the cases, respectively. Univariate Cox regression analysis showed that low expression of CDH1/E-cadherin (P = .002) and high expression levels of CDH2/N-cadherin (P < .001), SNAI1/Snail (P = .023), SNAI2/Slug (P < .001), and ZEB1 (P < .001) were associated with shorter progression-free survival. Here, we report for the first time the existence of EMT-like phenotype in EPNs. These factors could represent new prognostic and therapeutic targets in EPN.

Atypical cases of filariasis from a non-endemic area

Filariasis can present in many different ways and pose significant dilemma to the clinician. We report four atypical cases of filariasis which presented as abdominal mass, cervical lymph node enlargement, fever in pregnancy and nosocomial febrile illness respectively. All the four cases were treated successfully with oral antifilarial agents. It is essential to be aware of such atypical presentations of filariasis so that prompt therapy can be initiated.

Carcinoma showing thymus like elements: report of a case with EGFR T790M mutation

Carcinoma showing thymus‐like differentiation of the thyroid (CASTLE) is a rare tumor involving the thyroid and perithyroidal soft tissues. It shares morphological, immunohistochemical and molecular similarities with thymic carcinomas. Due to its relatively better prognosis, it needs differentiation from other primary and metastatic tumors of this region. A 40‐year‐old lady presented with a gradually progressive anterior neck swelling for one year. Imaging showed bulky right and left lobes of thyroid along with a solid soft tissue mass in the pretracheal region. Fine needle aspiration smears showed features of poorly differentiated carcinoma. Total thyroidectomy with excision of the mass revealed histopathological features characteristic of CASTLE, with evidence of thyroiditis in adjoining thyroid. Epidermal growth factor receptor (EGFR) assay revealed presence of EGFR T790M somatic mutation in exon 20. The same was not detectable on direct sequencing. We present a rare case of CASTLE, occurring in association with Hashimoto thyroiditis, with emphasis on cytological features and report for the first time the presence of a low level somatic mutation in EGFR (EGFR T790M mutation).