Role of intra-operative squash cytology in rosette-forming glioneuronal tumor of the fourth ventricle: a case report.

Rosette-forming glioneuronal tumor (RGNT) of the 4th ventricle is a newly described WHO grade I brain tumor included in recent WHO classification of CNS tumors. It is a biphasic tumor thought to originate from pluripotent progenitor cells of subependymal plate. Intra-operative diagnosis plays an important role, as complete surgical excision is the treatment of choice. We are reporting a case of RGNT in a 19 years-old young male emphasizing the intra-operative pathological pointers and their role in accurate diagnosis for the suitable surgical intervention.

Coexistent Rosai Dorfman disease and Langerhans cell histiocytosis in an Orbital mass: A Case Report.

INTRODUCTION: Rosai Dorfman disease (RDD) is a rare benign histiocytic proliferative disorder of lymph node sinuses. Langerhans cell histiocytosis (LCH) is a solitary or multisystem clonal proliferation of abnormal dendritic cells (Langerhans cells) with varied presentations. The co-occurrence of these two entities is quite rare. CASE DESCRIPTION: A six-year-old boy presented with multiple mass lesions in the neck since two years and a nodular lesion in right upper eyelid for the past 4 months. He was diagnosed with tubercular lymphadenitis 2 years back, and was given a course of anti-tubercular therapy (ATT) elsewhere. No improvement was seen. Fine needle aspiration cytology (FNAC) of the cervical lymph nodes revealed reactive lymphadenitis while lymph node biopsy showed features of RDD. Excision biopsy of the orbital mass showed features of both RDD and LCH. The patient was started on tablet prednisolone. Six months later, complete resolution of lymph node enlargement and remaining orbital mass was noted. Post operative contrast enhanced Magnetic Resonance Imaging of head and neck was normal. CONCLUSION: The coexistence of RDD and LCH may be a result of divergent differentiation from a common lineage or a de novo phenotypic evolution.

Quantitative proteomic analysis of GnRH agonist treated GBM cell line LN229 revealed regulatory proteins inhibiting cancer cell proliferation.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) receptor, a rhodopsin-like G-protein coupled receptor (GPCR) family member involved in GnRH signaling, is reported to be expressed in several tumors including glioblastoma multiforme (GBM), one of the most malignant and aggressive forms of primary brain tumors. However, the molecular targets associated with GnRH receptor are not well studied in GBM or in other cancers. The present study aims at investigating the effect of GnRH agonist (Gosarelin acetate) on cell proliferation and associated signaling pathways in GBM cell line, LN229. METHODS: LN229 cells were treated with different concentrations of GnRH agonist (10-10 M to 10-5 M) and the effect on cell proliferation was analyzed by cell count method. Further, total protein was extracted from control and GnRH agonist treated cells (with maximum reduction in cell proliferation) followed by trypsin digestion, labeling with iTRAQ reagents and LC-MS/MS analysis to identify differentially expressed proteins. Bioinformatic analysis was performed for annotation of proteins for the associated molecular function, altered pathways and network analysis using STRING database. RESULTS: The treatment with different concentrations of GnRH agonist showed a reduction in cell proliferation with a maximum reduction of 48.2% observed at 10-6 M. Quantitative proteomic analysis after GnRH agonist treatment (10-6 M) led to the identification of a total of 29 differentially expressed proteins with 1.3-fold change (23 upregulated, such as, kininogen-1 (KNG1), alpha-2-HS-glycoprotein (AHSG), alpha-fetoprotein (AFP), and 6 downregulated, such as integrator complex subunit 11 (CPSF3L), protein FRG1 (FRG1). Some of them are known [KNG1, AHSG, AFP] while others such as inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), ITIH4, and LIM domain-containing protein 1 (LIMD1) are novel to GnRH signaling pathway. Protein-protein interaction analysis showed a direct interaction of KNG1, a hub molecule, with GnRH, GnRH receptor, EGFR and other interactors including ITIH2, ITIH4 and AHSG. Overexpression of KNG1 after GnRH agonist treatment was validated using Western blot analysis, while a significant inhibition of EGFR was observed after GnRH agonist treatment. CONCLUSIONS: The study suggests a possible link of GnRH signaling with EGFR signaling pathways likely via KNG1. KNG1 inhibitors may be investigated independently or in combination with GnRH agonist for therapeutic applications.

Intraosseous solitary myofibroma of the orbit in an adolescent woman.

A 16-year-old woman presented with a painless, progressive, hard swelling in the left inferolateral orbital wall for the past 1 year. There was no diminution of vision or limitation of ocular motility. Imaging revealed an intraosseous, well-defined, expansile, soft tissue lesion in the inferolateral wall of the left orbit. A left anterior orbitotomy with complete surgical excision was performed. Histopathological evaluation of the specimen revealed fascicular pattern of spindle cells with a rich network of slit-like, branching blood vessels. Tumour cells exhibited smooth muscle actin and vimentin positivity but were negative for CD-34 and STAT-6. In absence of any systemic manifestation, a diagnosis of intraosseous solitary orbital myofibroma was made. The case highlights the importance of integrating clinical, radiological and histopathological features in overcoming the diagnostic challenge of differentiating myofibroma from other mesenchymal neoplasms. It also brings forth the importance of complete resection and curettage to prevent recurrence.

Unusual Tumours Hidden in Blind Eyes.

INTRODUCTION: This case report describes 3 cases of unsuspected neoplasms in previously blind eyes, with recent onset pain. Cases and observations: Case 1: Female with pain, redness in the non-seeing right eye (R/E) for two months. R/E had total cataract, low intraocular pressure and a well-defined globular mass lesion at the posterior pole, seen on ultrasound. Enucleation with an implant was done. Histopathology clinched the diagnosis of choroidal melanoma. Case 2: A 20-year male, developed pain, redness in left eye (L/E) for two months. L/E was blind since childhood, secondary to trauma. The patient underwent enucleation and detailed histopathological examination and immunohistochemistry supported a diagnosis of ependymoma with vascular malformation. Case 3: A 24-year male with pain, redness in L/E for six months, with decrease in size of eyeball. L/E had low vision since childhood. On examination, L/E was phthisical with diffuse conjunctival congestion, band-shaped keratopathy, cataract, and neovascularization of iris. Imaging revealed a small distorted globe with highly reflective mass along the posterior pole. Histopathology of the enucleated specimen confirmed the diagnosis of choroidal osteoma, with gliosis of the adjacent RPE. CONCLUSION: In the management of a painful blind eye, it is extremely important to rule out an intraocular malignancy, particularly in patients with recent onset of pain.

An Unusual Case of Primary Intracranial Germinoma with Diffuse Subarachnoid Spread Masquerading as Tuberculous Meningitis.

Central nervous system (CNS) germinomas often extend or disseminate into the ventricular and subarachnoid space. We present a case of primary CNS germinoma consisting mainly of meningeal dissemination, which is extremely unusual and must be kept in the differential diagnosis.

A cross-sectional study of the histopathology and immunology of alopecia areata: Unearthing the role of the Janus kinase-signal transducer and activator of transcription pathway.

BACKGROUND: Alopecia areata is an autoimmune disease that occurs as a result of the loss of the inherent immune privilege of the hair follicle. It has been recently demonstrated that the interferon-γ/interleukin-15 feedback loop that signals via the Janus kinase-signal transducer and activator of transcription pathway is critical to the breakdown of this immune privilege. AIMS: To evaluate the immunological distribution of CD4+ T-cells, CD8+ T-cells, phosphorylated signal transducer and activator of transcription 1 and study its relation with the clinical and histopathological findings of the disease. MATERIALS AND METHODS: A total of 30 patients of alopecia areata were included in the study. Following a detailed history and clinical examination, a scalp biopsy was performed. Histopathology was studied and immunohistochemistry was done to demonstrate the positivity and distribution of CD4+ T-cells, CD8+ T-cells and phosphorylated signal transducer and activator of transcription 1. RESULTS: The follicular count, number of anagen and terminal hair were found to be decreased, whereas the catagen, telogen and vellus hair were found to be increased in number. A peribulbar CD4+ T-cell infiltrate was seen in 70% cases, whereas a CD8+ T-cell infiltrate was seen in 83.3% cases. An intrabulbar CD4+ T-cell infiltrate was seen in 26.7% cases, whereas a CD8+ T-cell infiltrate was seen in 70% cases. Among the 25 hair follicles dermal papilla identified, 36.8% cases were found to be positive for phospho-signal transducer and activation of transcription-1. LIMITATIONS: The drawbacks of our study included a small sample size and the use of only vertical sectioning for the scalp biopsy samples. CONCLUSION: Phosphorylated signal transducer and activator of transcription 1 positivity as an indicator of signalling via the Janus kinase-1/2 pathway was seen in 36.8% of our cases highlighting the integral role of this pathway in the pathogenesis of alopecia areata.

Staging a great escape -Incidentally detected renal urothelial carcinoma with extensive squamous metaplasia presenting as pyonephrosis.

Incidentally, detected upper urinary tract urothelial carcinoma is a rare entity. We report the case of a 70-year-old female patient who presented with flank pain, pyuria, fever, and a unilateral nonfunctioning kidney with nephrolithiasis and pyonephrosis on pyelography. Routine imaging failed to identify a mass lesion. In an Indian setting, the clinical differential of tuberculosis was considered likely. A nephrectomy was performed in view of the poor perfusion and functional status of the right kidney. Histopathological examination of the kidney showed a tumor of urothelial origin arising at the renal pelvis displaying extensive squamous metaplasia. Such a near total metaplastic change is rare and has hitherto been undescribed in the renal pelvis. Activation of pleuripotent urothelial stem cells in the setting of chronic irritation and inflammation may be the pathogenetic process behind such an occurrence.

Metastasis from Intracranial Mesenchymal Chondrosarcoma: Report of a Rare Case.

Chondrosarcoma is a rare malignant tumor originating from cartilaginous tissue with a tendency to localize in the epiphysis of long and pelvic bones. Only 7% of all chondrosarcomas originate in the craniocervical region. Metastasis from intracranial chondrosarcoma is extremely rare with only two previously reported cases. We report on a young patient with intracranial chondrosarcoma who presented with extracranial metastasis 2 years after surgical excision of the primary lesion. Gross total excision combined with radiotherapy so far has led to a favorable outcome.

Childhood Lhermitte-Duclos Disease Progressing to Medulloblastoma in Bilateral Cerebellar Hemispheres: Report of Unusual Case.

BACKGROUND: Lhermitte-Duclos disease is an extremely rare pathologic entity characterized by a cerebellar mass composed of enlarged cerebellar folia containing abnormal ganglion cells. This entity usually presents in young and middle-aged adults and rarely in children. There is no study in the literature analyzing the long-term clinical course of this disease to assess the behavior primarily because of its rarity. CASE DESCRIPTION: We present our experience with a 7-year-old patient of Lhermitte-Duclos disease who was followed up for 5 years and found to have progressed to bilateral World Health Organization grade IV medulloblastoma. This case denotes the malignant potential of this rare disorder. CONCLUSIONS: LDD is seen rarely and demands a high degree of suspicion in patients presenting with cerebellar mass and/or imaging characteristics. It is prudent to keep these patients in close follow-up for early detection of malignant transformation.

Atypical presentation of cystic schwannoma of the sphenoid sinus: a nonsolitary mass with osseous, intracranial and cavernous sinus invasion.

Although nearly half of all schwannomas involve the head and neck region, nasal and paranasal sinus presentations are quite rarely seen. Cystic schwannoma, characterized by cyst formation lined by S-100 protein positive membrane-like structures is very uncommonly seen in sphenoid sinus with only a single previously reported case. Here we report a young patient of cystic schwannoma of the paranasal sinuses having epicenter in the sphenoid sinus. The tumor had caused extensive erosion of the skull base and paranasal sinuses and extended intracranially that radiologically mimicked as infected mucocele causing loss of vision. This case denotes the aggressive behavior of such uncommon tumors.

51-year old man with tingling, burning and progressive limb weakness.

Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy.

Granular ameloblastoma: report of two cases with atypical cytological aspects.

Ameloblastoma is an aggressive odontogenic tumor, which arises from odontogenic epithelium. Ameloblastomas can present in several clinical and histomorphological patterns. The granular cell variant accounts for only 3.5% to 5% of ameloblastomas. We have presented two cases of granular cell ameloblastoma (GCA) occurring in a 44-year-old and 50-year-old man, respectively. Case No. 1 on incisional biopsy was diagnosed as unicystic ameloblastoma (UA), which later after excisional biopsy was finally diagnosed as GCA owing to the features observed in excisional biopsied tissue. Case No. 2 on incisional biopsy showed darker and lighter stained cells arranged in small follicular pattern, and anastomosing cords. Meticulous immunohistochemistry, histochemical examination and careful literature search helped us to diagnose it as GCA. We have made an attempt to elucidate the diagnosis of GCA especially in cases of GCA with unusual granular component.

Metastatic Epithelioid Malignant Peripheral Nerve Sheath Tumor in a Known Case of Neurofibromatosis-1, Cytomorphological Appearance, and Critical Analysis of Immunohistochemistry.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue tumors commonly arising from nerve roots in the extremities with a predilection in neurofibromatosis (NF) patients. MPNSTs are known to behave aggressively, with worse prognosis in nonresectable cases, and a 5-year survival of about 52% and 15% in resectable and unresectable cases, respectively. Although cytological diagnosis in a known case of NF-1 is possible, however, in the absence of any associated syndrome in a sporadic case, it is very challenging to accurately diagnose this tumor. Till date, to the best of our knowledge, only three cases of epithelioid MPNST correctly diagnosed on cytological examination have been described. We are presenting another case of epithelioid MPNST in a 40-year-old patient with stigmata of NF-1 since childhood, diagnosed on fine-needle aspiration cytology from the left flank mass with subsequent histopathology from left inguinal lymph node metastasis.

Extradural Spinal Metastasis in Ovarian Mixed Germ Cell Tumor.

Ovarian germ cell tumors (GCTs) are rare and affect mainly young girls and women. Two histological groups are distinguished: dysgerminomas and nondysgerminomatous tumors. These tumors have initial good responses to surgery and chemotherapy in 80% cases, but >75% of patients die due to complications of disease progression. There are very few case reports of mixed GCT with extradural spine metastases. We report a rare case of a 17-year-old girl who had undergone left salpingo-oophorectomy with omental and peritoneal biopsy for ovarian GCT with extradural spinal metastasis.

Parasellar Chondrosarcoma in Three Young Patients: A Diagnosis of Caution.

Parasellar chondrosarcoma is rare slowly growing intracranial tumors. A correct diagnosis of these tumors is challenging for clinician due to overlapping location and simulation of clinical presentations with much common pituitary adenomas. We are reporting three young patients diagnosed to have parasellar chondrosarcoma highlighting the pathological features of importance required for confirm diagnosis.

Aspergillus Growth within Ventriculoperitoneal Shunt Tube.

Cerebrospinal fluid (CSF) shunt failure is commonly associated with infection or mechanical obstruction of the shunt system. A 4-year-old male child who had undergone multiple shunt revisions at another hospital for congenital hydrocephalus and later for shunt obstruction, presented with exposed shunt at the supraclavicular region. Shunt revision was performed. The CSF culture showed no growth; however, the histopathological examination of shunt tube showed Aspergillus growth inside the lumen of silicone tube well away from the tip of ventriculoperitoneal shunt. The skin biopsy from the exposed site revealed foreign body giant cell granulomatous reaction. The patient was discharged on postoperative day 6 without any complications. At 3 months follow-up, the patient is doing well. A growth of Aspergillus within the shunt tube prompted us to think of how the hardware can get infected and may remain a source of constant infection.

Intraocular Ependymoma With Blood-Filled Spaces: Neoplasm or a Reactive Process With Ependymal Differentiation-A Dilemma.

Intraocular glial lesions are rare and include retinal gliosis, hamartomas, and astrocytomas and rarely ependymomas. Ependymomas are slow-growing glial tumors preferentially arising in the central nervous system (CNS), occasionally presenting at sites outside the CNS, with only 2 cases of primary retinal ependymoma reported till date. We report herein the third such case of a 20-year-old male who presented with a painful blind eye. The enucleated specimen showed presence of a glial tumor with cells arranged in sheets as well as few true rosettes and pseudo-rosettes and an immunohistochemical profile similar to a classical ependymoma at usual sites in the CNS. Additionally, the presence of blood-filled spaces and few proliferating blood vessels made it a diagnostic challenge. All retinal glial lesions are positive for GFAP and S100. Therefore, immunostaining for EMA as well as the MIB-1-labeling index maybe vital in differentiating ependymomas from other intraocular glial lesions.

Is thyrogastric disease a potential setting for oncogenesis? Gastric adenoneuroendocrine carcinoma arising from Helicobacter pylori-associated atrophic gastritis in a patient with autoimmune thyroiditis.

Gastric mixed adenoneuroendocrine carcinoma arising from Helicobacter pylori-associated multifocal atrophic gastritis is exceedingly rare. An added association with autoimmune thyroiditis in this case highlighted a complex interplay between Helicobacter, autoimmunity and gastric atrophy. A 55-year-old hypothyroid female presented with hematemesis and a large polypoidal mass in the gastric fundus, suggestive of gastrointestinal stromal tumor on imaging and endoscopy. Histopathology revealed a tumor comprised of nests of monomorphic cells immunopositive for synaptophysin and chromogranin A admixed with malignant glands. Follow-up imaging revealed a heterogeneously enhancing residual gastric body wall. A completion total gastrectomy was performed. Histopathology displayed multifocal atrophic gastritis, occasional Helicobacter and nests of neuroendocrine cells. The patient also had markedly elevated levels of anti-thyroid peroxidase and anti-thyroglobulin. To the best of our knowledge, this is the first case of gastric adenoneuroendocrine carcinoma arising from H. pylori-associated atrophic gastritis, in a patient with autoimmune thyroiditis.