Cutaneous Histoplasmosis in HIV Seronegative Patients: A Clinicopathological Analysis.

BACKGROUND: Diagnosis of extrapulmonary histoplasmosis in HIV seronegative and immunocompetent patients is often challenging, so a high index of suspicion is required. Cutaneous manifestation of infection shows a wide spectrum of lesions including erythematous plaques; maculopapules; crusted, verrucous, or desquamative papules and nodules; abscesses; and mucocutaneous ulcers among others. Due to the variations in its clinical presentation, histopathology plays a very important role in the detection of spores and the confirmation of diagnosis. OBJECTIVES: The aim of our study was to analyze clinicopathological characteristics of cutaneous manifestations of biopsy-proven histoplasmosis in HIV seronegative individuals. We also examined the utility of Fite stain for the diagnosis of Histoplasma capsulatum on tissue biopsy sections. METHODS: This was a retrospective, observational study on 7 patients who were HIV seronegative and clinically manifested with isolated cutaneous lesions or disseminated disease. Skin biopsy from the lesions was performed on all 7 patients. In addition to H&E staining and special stains for detecting fungus, Fite staining was performed on all of the cases to study its utility in detecting H. capsulatum spores. RESULTS: The skin lesions were widely disseminated in all patients and the most common cutaneous lesions were papules, present in all 7 patients. On review of the H&E-stained slides, the most common pattern was histiocytic lobular panniculitis-like infiltrate observed in 4 cases. Fite stain highlighted the yeast as magenta-colored spores on a blue background in all cases, except for 1 with a granulomatous pattern. CONCLUSION: A primary cutaneous manifestation of H. capsulatum infection in non-HIV-infected individuals is extremely rare. Fite stain could aid in differentiating the spores of H. capsulatum from those of other fungi, Cryptococcus and Candida in particular.

Plasmablastic light chain myeloma presenting as pancytopenia: An unusual presentation.

Light chain myeloma (LCM) is an unusual neoplasm accounting for about 1 8% of all plasma cell myelomas. It is characterized by the absence of a detectable M protein in the serum and urine protein electrophoresis, altered free light chain ratio, bone marrow plasmacytosis and related organ or tissue damage. We report a 60-year-old man with LCM presenting with pancytopenia. Urine Bence Jones proteins were negative and serum protein electrophoresis did not reveal an M-band. However, bone marrow biopsy showed plasmablastic morphology. Subsequent immunohistochemistry showed lambda restriction and cells positive for CD138 and IgM.

Ciliated Foregut Cyst of Gallbladder: A First in Childhood and Review of Literature.

Ciliated foregut cyst (CFC) is a rare developmental anomaly. We report first case of CFC of gallbladder diagnosed in a 9-year-old child. CFCs are usually located above the diaphragm, commonly in a bronchus or oesophagus. A duplex gallbladder was originally suspected, but histology confirmed the CFC. gallbladder.

Invasive pulmonary mycosis due to Chaetomium globosum with false-positive galactomannan test: a case report and literature review.

In this case, the authors report Chaetomium globosum as a cause of invasive pulmonary infection in a patient with Wegener's granulomatosis. Fungal hyphae (KOH and Calcofluor) were seen on direct microscopy of lung biopsy sample and bronchoalveolar lavage (BAL) sample. C. globosum isolated on culture clinched the diagnosis of invasive pulmonary infection by Chaetomium spp. A positive galactomannan of serum and BAL was repeatedly seen and was utilised for follow-up and as prognostic marker in patient management. The patient was successfully treated with liposomal amphotericin B followed by voriconazole. All the Chaetomium infections reported till date since 1980 are reviewed. Chaetomium spp. with its unique ecology has a hidden clinical potential to cause invasive mould infections.

An Unusual Presentation of Disseminated Histoplasmosis: Case Report and Review of Pediatric Immunocompetent Patients from India.

Histoplasmosis is a progressive disease caused by dimorphic intracellular fungi and can prove fatal. Usually, it is present in immunocompromised individuals and immunocompetent individuals in the endemic zones. We report an unusual presentation of progressive disseminated histoplasmosis. The patient in the present case report was immunocompetent child and had fever, bone pains, gradual weight loss, lymphadenopathy and hepatosplenomegaly. Disseminated histoplasmosis (DH) was diagnosed on microscopic examination and fungal culture of bone marrow, blood, skin biopsy and lymph node aspirate. The patient died on seventh day of amphotericin B. In the absence of predisposing factors and classical clinical presentation of febrile neutropenia, lung, adrenal and oropharyngeal lesions, the disease posed a diagnostic challenge. Progressive disseminated histoplasmosis in children can be fatal despite timely diagnosis and therapy. In India, disseminated histoplasmosis is seen in immunocompetent hosts. All the pediatrics immunocompetent cases from India are also reviewed.

Spectrum of endoscopic gastric subepithelial lesions encountered on EUS-FNA: A single center experience.

BACKGROUND AND OBJECTIVES: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is a minimally invasive and reliable non-surgical technique for the diagnosis of gastrointestinal lesions. The present study aimed to evaluate the spectrum of lesions encountered in the gastric subepithelium on EUS-FNA at a tertiary care center. MATERIALS AND METHODS: Archival data of all patients undergoing EUS-FNA for gastric submucosal lesions over a period of 5 years was retrieved. Patient demographics, clinical presentation, and EUS findings were recorded along with the FNA results. RESULTS: A total of 78 EUS-FNA samples were analyzed. Material was adequate in 62 cases (79.48%) and inadequate in 16 cases (12.82%) patients due to scant cellularity. Of the adequate samples, 34 (43.5%) were reported as neoplastic while 20 (25.64%) were non-neoplastic, and 8 (10.25%) were reported as suspicious of a neoplasm. In the neoplastic category, the predominant diagnosis was of spindle cell neoplasm comprising gastrointestinal stromal tumor (13), benign neural tumor (03), leiomyoma (02), and spindle cell tumors (03). The latter could not be categorized further due to a lack of IHC material. The next common diagnosis was adenocarcinoma (06) followed by neuroendocrine tumor (02) and poorly differentiated carcinoma (01). The non-neoplastic lesions included non-specific pathology (15), inflammatory lesions (08), and one case each of tuberculosis, pancreatic rest, and Brunner gland hamartoma. Cell blocks for ancillary testing were available in 54 cases (65.23%) and follow-up was available in 42 cases (53.84%). CONCLUSION: EUS-FNA is a good modality for the diagnosis of gastric submucosal lesions with a high diagnostic yield.

Unmasking the Masquerade: Fine-Needle Aspiration Diagnosis of Dedifferentiated Liposarcoma Clinically Mimicking Lymphoma.

A preoperative diagnosis of dedifferentiated liposarcomas (DDLPS) on fine-needle aspiration cytology (FNAC) is rare with scarce indexed literature. Herein, we describe a case of DDLPS diagnosed on fine needle aspiration which was presumed to be a lymphoma clinically and radiologically.

Diagnostic Utility of Claudin4 and Comparison with BerEp4 as a Marker for Metastatic Adenocarcinoma in Serous Effusions.

INTRODUCTION: Fluid cytology for malignant cells is important for diagnosis and staging of malignancies. Morphological overlap between reactive mesothelial cells and adenocarcinoma poses challenges, for which many immunohistochemical markers like BerEp4 and MOC-31 have been used extensively. Claudin4 is a new marker with promising results; however, further studies are required to establish its role as a pan-carcinoma marker in serous effusions. This study aimed to determine the utility of Claudin4 in diagnosing metastatic adenocarcinoma in effusions and comparing its performance with BerEp4. METHODS: Claudin4 immunohistochemistry (IHC) was performed on effusion cell blocks (n = 60) reported as positive or suspicious for metastatic adenocarcinoma on cytology over a 1-year period and was scored for intensity (0-3) and percentage of positive cells (0-4). The results were compared with BerEp4 IHC and correlated with follow-up. Ten benign effusions were included as negative controls. RESULTS: Claudin4 IHC was positive in all 60 (100%) cases, irrespective of the primary site. BerEp4 IHC was positive in 58 (96.7%) fluids and negative in 2 (3.3%) cases. All 10 benign effusions were negative for Claudin4 and BerEp4. Claudin4 showed higher intensity and proportion scores as compared to BerEp4 in cases where tumor cells were predominantly singly scattered and was comparable to BerEp4 where tumor cells were arranged in groups. Sensitivity, specificity, PPV, and NPV of Claudin4 in our study was 100%. Sensitivity, specificity, PPV, and NPV of BerEP4 was 96.7%, 100%, 100%, and 83.3%, respectively. CONCLUSION: Claudin4 IHC staining results were comparable to BerEp4, irrespective of the primary site, and it performed better in cases where tumor cells were predominantly scattered singly.

Aberrant expression of multiple T cell markers on diffuse large B cell lymphoma: a case report.

BACKGROUND: Aberrant T cell antigen expression has been well documented in diffuse large B cell lymphomas. However, co-expression of multiple T cell antigens including CD3, which has been considered a specific marker for T cells is extremely rare. Awareness about such aberrant expression is important so as not to misdiagnose or wrongly classify a lymphoma. The aim of this article is to report such a case. CASE PRESENTATION: A 68-year-old postmenopausal lady, diabetic and hypertensive, presented with an axillary lump of one week's duration. There was no other relevant medical history. Ultrasonography revealed multiple hypoechoic cystic lesions varying in size from 3.9 to 4.2 cm3. Aspiration was suggestive of an infective pathology. Excision biopsy of the mass was diagnosed as diffuse large B cell lymphoma with aberrant T cell antigen expression. She received 4 cycles of chemotherapy after which she was lost to follow-up. CONCLUSION: The case presented as a diagnostic dilemma for the pathologist. The predicament lies in classifying it as a B cell lymphoma with an aberrant expression of T cell markers versus a T cell lymphoma with an aberrant B cell marker expression which has a significant implication on the treatment offered. This can be solved by looking at the expression of the B cell specific transcription factors. The key to diagnosis lies in the knowledge of their existence and the application of a panel of markers.

Allergy Testing - An Overview.

Childhood allergies pose huge economic burden and adverse effects on quality of life. Serum IgE has been considered a surrogate allergy marker for decades. Availability of several over-the-counter allergy tests add to confusion of partially trained caregivers. The present review focuses on current status of allergy testing in Indian scenario. Various in-vitro and in-vivo diagnostic modalities are available for allergy detection. Skin prick tests are useful for aero-allergies whereas oral challenge tests are best for identifying suspected food allergies. An allergy test should be individualized based on clinical features, diagnostic efficacy, and cost-benefit analysis.

Benefits of Pre-harvest Peripheral Blood CD34 Counts Guided Single Dose Therapy with PLERIXAFOR in Autologous Hematopoietic Stem Cell Transplantation: A Retrospective Study at a Tertiary Care Institute in India.

Peripheral blood is a convenient source of stem cells for hematopoietic stem cell transplantation. However, in autologous transplants, the harvest failure rates are high because of inadequate mobilization using G-CSF alone. Plerixafor is a potent mobilizer when used with G-CSF. However, its routine use is limited by high cost. This is a retrospective study done at a tertiary care oncology centre in India. All the harvest records were analyzed between Jan 2015 and Nov 2017. May 2016 onwards pre-harvest peripheral blood CD34 count was done in all cases of autologous transplants on day 4 of G-CSF therapy and they were given a single dose of Plerixafor if counts were < 20 cell per cumm. The results were compared amongst various groups. A total of 321 cases were analyzed. 172/321 were allogenic transplant cases of which 5% (n = 7) failed to achieve a target live stem cell dose of > 2 million per kg of the recipient. The overall failure rate in autologous group (n = 149) was 27% (n = 41) (p ≤ 0.001 auto vs. allo). The failure rate was higher (36%, n = 28/77) when no intervention with Plerixafor was done. The overall failure rate in the group treated with pre-harvest 34 count based single dose therapy of Plerixafor was 18% (n = 13/72, p = 0.01). However, within this intervention group, the patients who had pre-harvest peripheral blood CD34 above the desired cutoff had a higher failure rate of 21% (p = 0.13). Pre-harvest CD34 count based intervention with Plerixafor help optimizing the cost.

Predictive biomarkers in nonsmall cell carcinoma and their clinico-pathological association.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality worldwide. Genome-directed therapy is less toxic, prolongs survival and provides a better quality of life. Predictive biomarker testing, therefore, has become a standard of care in advanced lung cancers. The objective of this study was to relate clinical and pathological features, including response to targeted therapy (TT) and progression-free survival (PFS) with positive driver mutation. MATERIALS AND METHODS: Archival data of nonsmall cell carcinoma patients with Stage IV disease were retrieved. Those who tested positive for one of the four biomarkers (epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], MET, and ROS) were included. Patient demographics and clinical features were reviewed. Tumor histomorphology was correlated with oncological drivers. Treatment response, PFS, and overall survival were studied in three subcohorts of patients who received computed tomography (CT), CT followed by TT and those who received TT in the first line. RESULTS: A total of 900 patients underwent biomarker evaluation of which 288 tested positive. Frequency of the four biomarkers observed was 26.6% (229/860), 6.6% (51/775), 6.6% (5/75), and 5.1% (3/59) for EGFR, ALK, MET, and ROS-1, respectively. The median PFS for EGFR-mutated cohort was 12 months, whereas it was 21 months for ALK protein overexpressing cases. Patients treated with first-line tyrosine kinase inhibitors performed better compared to those who were switched from chemotherapy to TT or those who received chemotherapy alone (P < 0.05). CONCLUSION: Biomarker testing has improved patient outcome. Genome-directed therapy accords best PFS with an advantage of nearly 10 months over cytotoxic therapy.

Bladder Carcinoma Presenting as Paget's Disease of Vulva: An Uncommon Entity.

Paget's disease of the vulva is a rare intraepithelial neoplasm, accounting for <5% of all vulvar lesions. The underlying mechanisms of this disease are still poorly understood, however, diagnosing a Pagetoid lesion early is of prime importance as it may forewarn an underlying systemic malignancy. We discuss the case of an elderly female who was being conservatively treated for infectious lesion of the lower urinary tract and vulva for months. She was subsequently confirmed on histopathology with vulvar Paget's and underlying urothelial carcinoma, with the help of an extensive panel of immunohistochemistry.

Primary cutaneous non-Hodgkin's lymphoma, clinically mimicking a soft tissue sarcoma.

Primary cutaneous B-cell lymphomas (PCBCL) are a heterogeneous group of neoplasms with distinct biology and clinical course when compared to their nodal counterparts. They usually present as violaceous, erythematous plaques, and nonulcerated nodules, which are confined to skin at the time of presentation. We present an unusual case of primary cutaneous diffuse large B-cell lymphoma, clinically mimicking a sarcoma. This case highlights the uncommon aggressive behavior and ulcerated type of nodular lesions seen in PCBCL and also revisits the cytomorphological findings of the same.

Bisalbuminemia: A Rare Finding on Serum Electrophoresis.

Bisalbuminemia is an uncommon finding that is seen as bifid albumin peak on serum protein electrophoresis. We report here this unusual finding in an adult male diagnosed with multiple myeloma on routine workup.

Spectrum of clinicohematological profile and its correlation with average parasite density in visceral leishmaniasis.

BACKGROUND: Leishmaniasis is the prevalent in tropical and subtropical regions of the world. Demonstration of Leishman-Donovan (LD) bodies in the bone marrow aspirates (BMA) is vital to diagnosis of visceral leishmaniasis (VL). In the present study, we studied the clinicohematological parameters encountered in VL and correlated them with parasite load on BMA. METHODS: Retrospective analysis over 3 years was done; clinical details, biochemical profile, complete hemogram with peripheral smear findings, and BMA smears were reviewed and average parasite density (APD) calculated in each case. Multivariate analysis and tests of significance were applied. RESULTS: The study included 28 patients. Splenomegaly showed a positive trend with APD. rK39 antigen detection test was 100% positive in select cases. A strong negative correlation was observed between albumin to globulin ratio and grade of APD. BMA revealed hemophagocytosis (HPS) in 78.57% cases and it had a significant strong correlation with APD (P = 0.014). A significant correlation was also observed between APD and bone marrow plasma cell percentage (P = 0.01). LD bodies were noted in unusual locations such as within myelocytes (14.2%), plasma cells (7.1%), and megakaryocytes (10.7%). CONCLUSION: HPS and bone marrow plasmacytosis were two statistically significant findings, which showed positive correlation with parasite load. The presence of these two findings should prompt hematopathologists for more focused search of hemoparasites in BMA to arrive at a definitive diagnosis. This will avoid unnecessary workups and improve the prognosis. To the best of our knowledge, a statistical correlation between APD and clinicohematological parameters has never been previously studied.

Urothelial carcinoma of urinary bladder with exclusive heterologous component of epithelioid rhabdomyosarcoma at metastatic site.

Urothelial carcinoma of urinary bladder with divergent differentiation into rhabdomyosarcoma (RMS) is an extremely uncommon aggressive phenomenon. We present a case of a 74-year-old male with bladder carcinoma which metastasized to the abdominal wall as epithelioid RMS. To the best knowledge of our literature searches, an oligometastasis of exclusive heterologous component has not been described before. The clinical, radiological, and immunohistochemistry profile of the patient supported the monoclonal nature of the tumor.

Study of Proliferating cell nuclear antigen expression and Angiogenesis in Urothelial neoplasms: Correlation with tumor grade and stage.

BACKGROUND: Urinary bladder carcinoma ranks ninth in worldwide cancer incidence. About 74,000 new cases were diagnosed in 2015 alone and 16,000 persons died of the disease. Since histopathology is considered gold standard for diagnosis, it is prudent to look for potential tumor proliferation and predictive markers in such a prevalent malignancy so as to alert surgical and medical oncologists for timely intervention and provide better patient-tailored therapy. AIMS: This study is to analyze the role of potential biomarkers-proliferating cell nuclear antigen (PCNA) and angiogenesis using CD31 in urothelial neoplasms in relation to tumor grade and stage. METHODS: Histopathology slides were prepared from transurethral resection of bladder tumor chips and assessed by three independent observers as per the WHO/International Society of Urologic Pathology criteria 2016. Representative sections were subjected to immunohistochemistry. PCNA labeling index (PCNA LI) and mean vessel density (MVD) were calculated. STATISTICAL ANALYSIS: Tests of analysis were applied as appropriate. A statistical P < 0.05 was considered significant. RESULTS: Forty-nine patients were analyzed. PCNA LI increased with grade and stage. PCNA was significantly higher in noninvasive papillary urothelial carcinoma high grade (NIPUCHG) than in noninvasive papillary urothelial carcinoma low grade (NIPUCLG) and in infiltrating urothelial carcinoma as compared to NIPUCLG. MVD also increased with tumor grade and stage; however, a significant difference was observed only between infiltrating urothelial carcinoma and papillary urothelial neoplasm of low malignant potential. A cutoff value of 73% for PCNA and 49 vessels/high-power field for CD 31 showed 100% accuracy to differentiate between noninvasive papillary urothelial carcinoma high grade and NIPUCLG. No association was observed between tumor recurrence and PCNA or CD31 expression. CONCLUSION: PCNA and CD31 when used together are valuable markers to help classify urothelial neoplasms in limited tumor material. However, larger prospective studies are required for better prognostication.

Cytology of primary vaginal melanoma: An unusual report on fine needle aspiration.

Primary malignant melanoma of the vagina is an extremely uncommon malignancy comprising of less than 10% malignancies of the female genital tract and 0.3% of all melanomas. Melanoblasts are neural crest derivatives and are notorious for causing primary cutaneous neoplasms. However, they involve virtually every organ of the body including eye, intestines and ocular mucosa, probably due to aberrancies in cell migration. Vagina is a rare site and primary melanoma of the vagina occurs in postmenopausal women with vaginal discharge, bleeding, or mass as common presenting complaints. Only a handful of case reports are available describing this entity on biopsy and PAP smear samples; however, fine needle aspiration has seldom been discussed. In the present report we discuss a case of an elderly female who complained of mass protruding through the vaginal opening, FNAC was done from the mass as well as from the right inguinal lymph node. An extensive clinicoradiological workup, and immunohistochemical confirmation is essential to rule out metastatic lesions and confirm primary. Diagn. Cytopathol. 2017;45:252-256. © 2016 Wiley Periodicals, Inc.