Immunocytochemistry using Liquid-based Cytology: A Tool in Hormone Receptor Analysis of Breast Cancer.

CONTEXT: Efficacy of immunocytochemistry (ICC) in determining molecular biomarkers like estrogen receptor (ER), progesterone receptors (PRs), and human epidermal growth factor receptor-2 (HER2). AIMS: To evaluate biomarkers using ICC in breast cancer as per American Society of Clinical Oncology/College of American Pathology (ASCO/CAP) guidelines. SETTINGS AND DESIGN: The study was conducted over a period of 2 years from September 2012 to August 2014 and is the first such study in eastern India. MATERIALS AND METHODS: Fine needle aspiration cytology (FNAC) was done for suspected cases of breast cancers and slides were prepared using ThinPrep (TP) technology of liquid-based cytology (LBC) for ICC and corresponding biopsy specimens were processed as formalin fixed paraffin embedded (FFPE) sections for comparison. Both the LBC slides and tissue sections were subjected to immunostaining for ER, PR, and HER2. ICC was evaluated by Allred Scoring and IHC by Quick Scoring. STATISTICAL ANALYSIS USED: Statistical analysis done by Wilconxon Signed rank test on the SPSS program, Chicago, Illinois, USA. The results of ICC and IHC were compared by evaluation of sensitivity, specificity, kappa-value (k-value), positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The comparison of ICC with immunohistochemistry (IHC), ER, and PR showed very good correspondence rate, sensitivity, specificity, NPV, PPV, and agreement with k-value; whereas for HER2 the results were only good. CONCLUSION: ICC using LBC can be a useful tool in assessing biomarkers in advanced cases of breast cancer where surgery is not possible or cases where ASCO/CAP guidelines for management are not followed.

Prognostic Significance of Epidermal Growth Factor Receptor in Patients of Glioblastoma Multiforme.

INTRODUCTION: Glioblastoma Multiforme (GBM) is the most aggressive glial tumour with hallmark characteristics of rampant proliferation of glial cells along with high pleomorphism, necrosis, endothelial proliferation and high MIB-1 labeling index (cell proliferation marker). These tumours are managed by surgery followed by Radiotherapy (RT), Chemotherapy (CT) and adjuvant CT Temozolomide (TMZ). AIM: To evaluate Epidermal Growth Factor Receptor (EGFR) protein expression in GBM patients. MATERIALS AND METHODS: The study comprised of 52 cases of GBM diagnosed by histomorphology from biopsy specimens. Ancillary techniques like Immunohistochemistry (IHC) for Glial Fibrillary Acidic Protein (GFAP), cell proliferation marker (MIB-1 labeling index, P53 expressions) were done in all cases. EGFR protein expression was assessed by IHC as the percentage of positive tumour cells in hot spots (10 high power fields). Response to therapy was assessed at three months post therapy by using World Health Organization (WHO) Response Evaluation Criteria In Solid Tumours (RECIST) guideline. Statistical analysis was performed by using IBM-Statistical Package for Social Sciences (SPSS) software, version 20. The p-value of ≤ 0.05 was considered significant. The mean survival of the patients was calculated using unpaired t-test and ANOVA (analysis of variance) test. RESULTS: Out of 52 cases, thirty cases was EGFR positive and 22 cases were EGFR negative. Response to therapy was evident in 33 (63.5%) cases and 19 cases (36.5%) were non responders. The responders with EGFR negative were 86.4% and EGFR positive were 46.7% with a p-value of 0.003. The mean survival among EGFR positive and negative GBM were 315.73±257.54 and 657.91±305.88 days respectively with a significant p-value of 0.001. CONCLUSION: EGFR negative patients respond better to therapy along with longer duration of survival as compared to EGFR positive patient.

Delivery of Dual Drug Loaded Lipid Based Nanoparticles across the Blood-Brain Barrier Impart Enhanced Neuroprotection in a Rotenone Induced Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological hallmarks of PD. In this context, amalgamation of curcumin and piperine having profound cognitive properties, and antioxidant activity seems beneficial. However, the blood-brain barrier (BBB) is the major impediment for delivery of neurotherapeutics to the brain. The present study involves formulation of curcumin and piperine coloaded glyceryl monooleate (GMO) nanoparticles coated with various surfactants with a view to enhance the bioavailability of curcumin and penetration of both drugs to the brain tissue crossing the BBB and to enhance the anti-parkinsonism effect of both drugs in a single platform. In vitro results demonstrated augmented inhibition of αS protein into oligomers and fibrils, reduced rotenone induced toxicity, oxidative stress, and apoptosis, and activation of autophagic pathway by dual drug loaded NPs compared to native counterpart. Further, in vivo studies revealed that our formulated dual drug loaded NPs were able to cross BBB, rescued the rotenone induced motor coordination impairment, and restrained dopaminergic neuronal degeneration in a PD mouse model.

Efficacy of liquid-based cytology versus conventional smears in FNA samples.

BACKGROUND: Liquid-based cytology (LBC) is fast becoming a useful method in evaluating both gynecological and non-gynecological preparations, including fine needle aspiration (FNA) cytology. Even distribution of cells, decreasing obscuring background elements like blood and mucus, well preserved nuclear and cytoplasmic details and rapid fixation helps in better visualization of cells. AIM: This study was conducted to asses the diagnostic accuracy of liquid-based cytology versus conventional smears in fine needle aspiration samples. STUDY DESIGN: In this prospective study, we had 110 cases, including 30 cases of breast, 40 of lymph node, 10 of salivary glands, 18 of thyroid and 12 of bone and soft tissue. In each case, two passes were performed. The first pass was for conventional preparation (CP) and the second pass yielded material for thin-prep (TP) preparation. Both CP and TP smears were compared for cellularity, background blood and necrotic cell debris, cell architecture, informative background, presence of a monolayer of cells and nuclear and cytoplasmic details by a semiquantitative scoring system. Wilcoxon's signed rank test on an SPSS program was used for statistical analysis. RESULTS: Diagnostic accuracy was better in LBC smears compared with CP smears due to lack of background debris and better cell morphology, which was performed according to Wilcoxon's signed rank test, yielding a P-value of <0.001. However, in some cases, because of a decrease in cell size, clustering and altered background in LBC, a support of CP was essential. CONCLUSION: LBC performed on FNA samples can be a simple and valuable technique. Only in few selected cases, where background factor is an essential diagnostic clue, a combination of both CP and TP is necessary.

Aqueductal Stenosis Has a New Dimension--Aspergillosis: A Rare Case Report and Review of the Literature.

BACKGROUND: Cerebral aspergillosis, often encountered in immunocompromised patients, is almost always fatal despite radical surgical and medical management and frequently is a finding at autopsy. Attempts at fungal isolation often are unsuccessful, and a high index of radiologic suspicion is necessary. CASE DESCRIPTION: A premature, 5-month-old female infant, born via normal vaginal delivery, presented with a progressive increase in head size since birth, delayed developmental milestones, and intermittent vomiting for 1 month. There was no history of trauma and no evidence of diabetes mellitus or hypertension, family history of tuberculosis, gestational diabetes, jaundice, or febrile eruptions. Neonatal jaundice was present after day 1, remained for 2 days, and was treated with phototherapy. Findings of the general and systemic examinations were unremarkable. Findings of a neurologic examination revealed a hypoactive infant with papilledema and extensor plantar bilaterally. Computed tomography scan of brain showed hydrocephalus attributable to aqueductal stenosis. On endoscopic third ventriculostomy, dense, friable, whitish yellow, nonvascular masses were encountered in the third ventricle, obstructing it. Her endoscopic third ventriculostomy success score was 10 + 0 + 10 = 20%. Histopathologic examination and culture revealed Aspergillus flavus. A week later, a medium-pressure ventriculoperitoneal shunt was done, and voriconazole was added. RESULTS: At discharge on the 7th postoperative day, 4 weeks and 12 weeks later (ie, first and second follow-up) the child was active, playful, and feeding normally. The first reported case of an aqueductal stenosis due to aspergillosis was in 2000 by van Landeghem FK et al. (Clin Neuropathol 19:26-29, 2000). To the best of our knowledge, this may only be the second reported case of hydrocephalus attributable to aqueductal stenosis caused by Aspergillosis. In conclusion, aspergillosis should not be ruled out as a differential diagnosis in aqueductal stenosis, even when the patient seems to be immunocompetent.

A case of multiple myeloma presenting as scalp swelling with intracranial extension.

Multiple myeloma is a malignant neoplasm of bone marrow affecting plasma cells. It is usually detected in skull bone with characteristic features of multiple punched-out lesions. Its presentation as a solitary scalp swelling with underlying skull bone erosion and intracranial extension is very rare. A 35-year-old female presented to us with complains of rapidly growing left-side scalp swelling with right-side paresis and simple partial seizure of right upper limb. Local examination, X-ray skull, CT scan, and MRI of brain were suggestive of a malignant lesion. Near total excision of lesion was done. Histopathological study was suggestive of plasmacytoma of skull. Bone marrow study further confirmed it as a case of multiple myeloma. Cases presenting with solitary osteolytic skull lesions, possibility of plasmacytoma, or multiple myeloma should be kept in mind.

Extranodal Rosai-Dorfman disease in a carpal bone.

We report a case of extranodal Rosai-Dorfman Disease (RDD) of the scophoid in a 52-year old female. The patient presented with pain, swelling, and tenderness on deep palpation of the left wrist. Clinicoradiological diagnosis was osteomyelitis or tenosynovitis and curettage was performed on the lytic lesion over scaphoid to procure tissue. Diagnosis was made by histomorphology supported by immunostaining. The patient was managed conservatively with resolution of the lesion.

Primary intraspinal ganglioneuroblastoma of the thoracic spine: a rare case report.

Cerebral ganglioneuroblastoma is an embryonal tumor of the central nervous system, which has been rarely encountered into the spinal cord. The standard treatment for ganglioneuroblastoma is complete surgical excision. A 15-year old boy was presented with cord compression. Magnetic resonance imaging revealed an intradural and intramedullar enhancing lesion over T2 spine. A histomorphological diagnosis was made in the presence of immature small round cells admixed with a good number of ganglion cells. The morphological diagnosis was verified by immunohistochemistry. This is the first reported case of compressive myelopathy in the thoracic region of the spine.

Primary intraosseous malignant peripheral nerve sheath tumor of spine with a giant paraspinal and retrospinal subcutaneous extension.

BACKGROUND: According to World Health Organization (WHO) classification of tumors, malignant peripheral nerve sheath tumors (MPNST) encompass the tumors, which were previously termed as malignant schwannoma, neurogenic sarcoma, and neurofibrosarcoma. These are rare tumors constituting only 5% of all malignant soft tissue tumors. As per their name, they arise from the malignant proliferation of cells forming sheath of a nerve root. They cause spinal cord compression, secondary changes in the surrounding bone with variable amount of tumor tissue going into the paraspinal space. However, purely intraosseous origin of the MPNST with no visible connection with a nerve root or dura is rare and few cases have been described in the literature. CASE DESCRIPTION: We present a primary intraosseous MPNST arising from the body of a thoracic spine with a minimal intraspinal component. However, there was a huge tumor part occupying the paraspinal and retrospinal region. The latter component was so large that it extended to lie just beneath the skin. The intraspinal component was confined to only one level. The giant extraspinal part was spanning multiple corresponding spinal level. We could not find such presentation in the literature. CONCLUSION: Gross total removal (GTR) followed by adjuvant chemo-radiotherapy is the optimal treatment for MPNST of spine. In case of multiple laminectomy or gross spinal instability, spinal instrumentation makes the treatment protocol complete.

Melanotic choroid plexus carcinoma of the posterior fossa.

BACKGROUND: The pigmented or melanotic variant of choroid plexus carcinoma is very rarely encountered. CASE REPORT: We report herein a case of melanotic or pigmented choroid plexus carcinoma in the posterior fossa of an 11-year-old female. CONCLUSIONS: A histopathological study supported by immunohistochemistry helped the authors to diagnose this rare entity. How to differentiate this tumor from pigmented papillary medulloblastoma, cerebellar papillary ependymoma, and metastatic malignant melanoma is discussed.

Peritoneal Keratin Granuloma Masquerading as Disseminated Carcinoma.

Peritoneal keratin granuloma is a rare lesion included under granulomatous lesions of the peritoneum. It can be of infectious and non-infectious etiology. The lesion presents as a large intra-abdominal necrotic mass often misinterpreted clinically as a disseminated carcinoma. We report a case of peritoneal keratin granuloma in a 50-year-old male following peritonitis. Histomorphology revealed laminated keratin deposits with giant cell reaction. Follow-up data of this granuloma suggests that it has no prognostic significance.

A case of post kala-azar dermal leishmaniasis in India.

Post kala-azar dermal leishmaniasis (PKDL) is a rare disease. This is a solitary case report from Orissa, India. We describe a case of PKDL in a 55-year-old male who presented with multiple nodular lesions over face, trunk, and extremities. The patient had been to an endemic area of kala-azar and had a previous history of leishmaniasis. Fine needle aspiration cytology samples from skin nodules revealed Leishmania amastigotes.

A Rare Malignant Triton Tumor.

Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation, malignant triton tumor, has a rare incidence. We report such a case in a 40-year-old male who presented with a mass over the buttock. He was a previously diagnosed case of neurofibroma in the same area. Histomorphology supported by immunostaining with S-100 protein confirmed the diagnosis. Malignant triton tumor has a poor prognosis owing to its aggressive biological behavior. The fact that the presence of this tumor in the buttock region is extremely rare has prompted the authors to report this case.

Familial complete androgen insensitivity syndrome with prostatic tissue and seminal vesicles.

INTRODUCTION: Complete androgen insensitivity syndrome (CAIS) is a rare androgen receptor function disorder where phenotypic female has a male genotype. They mostly present as bilateral inguinal hernias containing testes. Uterus and cervix are absent. MATERIALS AND METHODS: The authors present a case of CAIS in a 22-year-old female where the presence of testes, prostatic tissue and seminal vesicles was confirmed by ultrasonography, hormonal analysis, operative findings and histopathological study. She was second of the two sisters and her elder sister was also diagnosed with CAIS. CONCLUSION: High levels of testosterone seen in CAIS can stimulate Wolffian duct development/differentiation. Gonadectomy is advisable in such patients to avoid future neoplastic changes.

Endovascular papillary angioendothelioma in an elderly female.

Endovascular papillary angioendothelioma (EPA) is a rare vascular tumor of low grade malignancy, encountered primarily in children. However some cases have also been reported in adults. A sixty year old female with EPA is described here. She presented with a swelling in the neck. Total surgical excision was performed. Histomorphology revealed anastomosing lymphatic channels showing intraluminal papillary fronds with hyaline vascular cores and hobnailing of endothelial cells. A diagnosis of EPA was made based on this picture. This tumor is recurrent and nodal metastasis has been reported in some cases.

Plasma cell leukemia masquerading as ALL-L3--a case report.

Plasma cell leukemia (PCL) is a rare type of plasma cell dyscrasia. It is diagnosed when circulating plasma cells (PC) are more than 20%. We present a case of PCL in a 62-year-old female. Peripheral smear revealed more than 80% atypical vacuolated plasma cells (Mott cells) almost mimicking Burkitt cells of Acute Lymphoid Leukemia-L3 (ALL-L3). Bone marrow aspirate revealed few mature myeloma cells for which a diagnosis of PCL was thought of. Serum electrophoresis showed a positive M-band and X-ray revealed lytic lesions over femur & pelvic bones. A final diagnosis of PCL was given.

Cerebellar haemangioblastoma mimicking renal cell carcinoma--a case report.

Haemangioblastoma is a rare benign vascular tumor commonly seen in the cerebellum. There is a striking histologic similarity between cellular variant of haemangioblastoma and metastatic renal cell carcinoma. We present a case of haemangioblastoma in a 32-year-old male. Histology revealed a highly vascular tumor composed of clear cells in a lobular arrangement.