Breast Carcinoma - A Comparative Study of Immunohistochemistry and Fluorescence in Situ Hybridization for Her-2 Assessment and Association of ER, PR, HER-2 and Ki-67 Expression with Clinico-Pathological Parameters.

Background & Objective: Breast cancer is the most common cancer in developed and developing countries. This study mainly addresses the issue of an equivocal result in IHC, which then needs further assessment if the patient has to receive targeted therapy. The study aimed to detect the expression of Her2/neu protein in breast cancer by immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) and evaluate concordance and discordance between the two methods. Also, the clinicopathological parameters in these patients were studied in association with ER, PR, HER-2, and Ki-67. Methods: This study was conducted on 34 female carcinoma breast specimens, including core biopsies and mastectomies. Each case underwent histopathological and immunohistochemical studies for (Estrogen Receptor) ER, (Progesterone Receptor) PR, (Human Epidermal growth factor Receptor 2) HER-2, and Ki-67. In addition, FISH was done on all the samples to detect Her2 gene amplification. Results: The overall concordance between the two tests was 79.41% while the concordance between the two tests in equivocal cases, was 14.3%. ER/PR expression and HER-2 amplification were inversely associated. Also, Ki-67 expression was not associated with the side size of the lesion, lymphovascular invasion, and lymph node metastasis. Age less than 50 at presentation and infiltrating ductal carcinoma histological type showed increased proliferation index. Conclusion: The highest concordance between FISH and IHC was noted in IHC positive and negative cases, whereas IHC equivocal cases showed low concordance. FISH accurately determines the assessment of HER2 expressions in equivocal cases.

Loss of miR-936 leads to acquisition of androgen-independent metastatic phenotype in prostate cancer.

Prostate cancer (PCa) progresses from a hormone-sensitive, androgen-dependent to a hormone-refractory, androgen-independent metastatic phenotype. Among the many genes implicated, ANXA2, a calcium-dependent phospholipid binding protein, has been found to have a critical role in the progression of PCa into more invasive metastatic phenotype. However, the molecular mechanisms underlying the absence of ANXA2 in early PCa and its recurrence in advanced stage are yet unknown. Moreover, recent studies have observed the deregulation of microRNAs (miRNAs) are involved in the development and progression of PCa. In this study, we found the down-regulation of miR-936 in metastatic PCa wherein its target ANXA2 was overexpressed. Subsequently, it has been shown that the downregulation of miRNA biogenesis by siRNA treatment in ANXA2-null LNCaP cells could induce the expression of ANXA2, indicating the miRNA mediated regulation of ANXA2 expression. Additionally, we demonstrate that miR-936 regulates ANXA2 expression by direct interaction at coding as well as 3'UTR region of ANXA2 mRNA by luciferase reporter assay. Furthermore, the overexpression of miR-936 suppresses the cell proliferation, cell cycle progression, cell migration, and invasion abilities of metastatic PCa PC-3 cells in vitro and tumor forming ability in vivo. These results indicate that miR-936 have tumor suppressor properties by regulating the over expression of ANXA2 in hormone-independent metastatic PCa. Moreover, our results suggest that this tumor suppressor miR-936 could be developed as a targeted therapeutic molecule for metastatic PCa control and to improve the prognosis in PCa patients.

Endometriosis: A Clinicopathological Study in a Tertiary Care Hospital.

Background Endometriosis (EM) is an estrogen-dependent disease characterized by the presence of endometrial gland and stroma outside the uterus. It is commonly seen in the reproductive age group and is a leading cause of infertility. Patients present with chronic pelvic pain, menstrual abnormalities, dyspareunia, or mass per abdomen. Surgical excision is the treatment of choice with postoperative medications and progesterone agents. Aims and Objectives This study aims at determining the distribution of EM in terms of age, parity, symptoms, site, morphological features. We also analyzed the management of EM in these cases. Methodology This is a retrospective study done in a tertiary care hospital in Mangalore, India. The case records of 77 histopathologically confirmed cases of EM during the 7 years between June 2012 and May 2019 were studied. Demographic profiles, parity, presenting complaints, site of the lesion, morphological features, treatment given, follow-up, and recurrence were noted and analyzed. Results Of the 77 patients with EM, the most common age group was the fourth decade (40%). The majority (31, 40.25%) of the patients in this study were nulliparous. Chronic pelvic pain was the most common symptom. The most frequent site was ovary. Conclusion The most frequent site of EM is ovary, leading to infertility. With the advent of laparoscopy, early diagnosis and excision have been feasible. The histopathological examination should be done for confirmation. Awareness of this disease among health care professionals is necessary whenever a woman in reproductive age presents with chronic pelvic pain and infertility.

Cytogenetic and cytokine profile in elderly patients with cytopenia.

In the elderly with cytopenia, the diagnosis of myelodysplastic syndrome (MDS) may be missed. Cytokine levels contribute to the pathology of MDS. Hence, the objectives were to evaluate cytogenetic profile as a prognostic indicator in risk stratification and cytokine levels as a screening tool in patients with cytopenia for diagnosis. Over 2 years (2016-2018), 150 elderly patients were screened. MDS diagnosis was confirmed by morphology. Interleukin-2 (IL-2) and IL-6 levels were assessed in 50 patients, and karyotyping was performed in 20 confirmed cases of MDS. Age-matched healthy controls were used for comparison of cytokine levels. Among 150 patients, 88.6% had anemia, including nutritional anemia (51.2%). MDS diagnosis was confirmed in 35 patients. In 15 patients, unexplained cytopenia (UC) was present. Karyotyping in 20 MDS patients was normal in 15 (75%) patients and revealed a complex karyotype in four (20%) patients and double chromosomal abnormality in one (5%) patient. The Revised International Prognostic Scoring System (IPSS-R) scored 91% in the low-risk group and 9% (n = 3) in the high-risk group; the latter three developed acute myeloid leukemia (AML) and two of them had a 7q deletion. Among the 15 cases of UC, one patient died from refractory anemia. No significant difference in levels of IL-2 and IL-6 were found between MDS and UC patients when compared with healthy controls, as well as between different risk groups and karyotypes. A significant difference in IL-2 levels was found in MDS patients with disease progression and with stable disease. On the basis of the findings, it is suggested that IL-2 levels will help in predicting disease progression.

Histomorphological Assessment of Formalin versus Nonformalin Fixatives in Diagnostic Surgical Pathology.

Introduction Fixation is the critical step in the preservation of tissues in diagnostic pathology. The formalin is an economical and excellent fixative with the inherent property of adequate fixation. The well-established side effects of formalin include mucosal irritation, upper respiratory diseases, and corrosive injury to the gastrointestinal tract. In addition, substantial evidence exists regarding the potential role of formaldehyde as a human carcinogen. The carcinogenic and toxic effects of formalin encourage searching for alternative fixatives for tissue fixation. However, "the formalin dogma" has severely hampered the search for alternative fixatives for many years. Material and Methods Ninety tissues of liver and skeletal muscle obtained during autopsies were immersed in adequate amounts of the following fixatives: formalin (10%), methyl alcohol (70%), and acetone (100%). The comparison among the three was made based on time for fixation, preservation of tissue architecture, cell borders, cytoplasm, nuclear contours, chromatin texture, and uniformity of staining. Results The tissue preserved in formalin undergoes rapid fixation compared with alcohol and acetone. The tissue architecture, cell border characteristics of alcohol and acetone was found satisfactory compared with formalin. The cytoplasm and nuclear contour were superior with the formalin. The chromatin texture and uniformity of staining were similar with all the three fixatives. Conclusion The formalin is considered superior to most of the parameters, whereas both methyl alcohol and acetone showed nearly equivalent scores. Hence, owing to the potential human health hazards and carcinogenicity of formalin, no rational reasons hamper the complete substitution of formalin with alternative fixatives such as alcohol and acetone in diagnostic pathology and medical research.

Expression of E cadherin and Ki 67: Emerging Prognostic Markers in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer which lacks effective target therapy. Expression of biomarkers is one of the important deciding factors for treatment strategies. The aim of this study was to evaluate expression of E cadherin and Ki 67 in relation to clinicopathological features. This prospective observational study included 141 cases of TNBC. Immunohistochemical staining was employed to analyze two biomarkers: E cadherin and Ki 67 on formalin-fixed paraffin-embedded tumor samples obtained from patients defined as TNBC. The age of the patients ranged from 26 to 84 years. Positive lymph nodes were found in 82 (58.1%). The tumor was grade 3 in 105 (74.4%). The E cadherin receptor was positive in 83 (58.8%). The Ki Index was > 10% in 89 (63.12%). The Ki 67 expression was significantly associated with a high nuclear grade (p = 0.000). The significant association noted between loss of E cadherin expression and positive lymph node (p = 0.0296). According to the results, TNBCs are frequently associated with the younger age groups, and the majority is poorly differentiated. The majorities of these have high expression of the Ki 67 and significantly associated with the higher nuclear grade. Loss of E cadherin was significantly associated with positive lymph nodes. Hence, evaluating the expression of E cadherin and Ki 67 routinely would be helpful for evaluating prognostic implications.

Giant cells in soft tissue tumors! Is it a clue to diagnosis or cytologists mystery??? An unusual case report.

Giant cells in soft tissue (ST) tumors are rare, pose great challenges to treating clinicians, and diagnosing pathologists. Common lesion with giant cells includes benign conditions such as nodular fasciitis to highly malignant lesions such as giant cell variant of malignant fibrous histiocytoma and extraskeletal osteosarcoma. Giant cell tumors of ST, extension of bony lesion to the ST are also rare possibilities. Recently, giant cell fibroblastoma and dermatofibrosarcoma protuberans have also been added to this list. These tumors show unpredictable behavior; some patients are cured by simple surgical excision whereas others develop metastasis. Diagnosing these in cytology is still more challenging. We report here a rare case of a giant cell-rich dermatofibrosarcoma protuberans in a 23-year-old male who presented with ST lesion in left forearm since 6 months. The lesion was predicted in fine-needle aspiration cytology and confirmed later with histopathology. When evaluated along with clinical features, the cytological features are very useful to distinguish between these tumors with giant cell morphology.

Basaloid Squamous Cell Carcinoma of Scalp From A Pre-Existing Cylindroma Metastasising To Brain: A Rare Case Report.

Squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer and accounts for 90% of head and neck malignancies. Intracranial metastases of SCC are extremely rare. We are reporting a case of 55-year-old female with history of recurrent swelling over right side of forehead which was previously reported as cylindroma. CT scan of head revealed irregular lytic areas in right frontal bone suggestive of erosion. There were multiple small, rim enhancing lesions in bilateral parietal regions. Clinically it was diagnosed as malignant adnexal tumour. Wide excision of the lesion revealed features of invasive basaloid squamous cell carcinoma, probably a malignant transformation of the pre-existing cylindroma.

Molar Pregnancy Presents as Tubal Ectopic Pregnancy: A Rare Case Report.

The incidence of hydatidiform mole is 1 per 1000 pregnancies. The occurrence of hydatidiform mole in ruptured tubal pregnancy is very rare. We report an unusual case of molar pregnancy in the right fallopian tube which presented as an adherent adnexal mass. The present case conveys the importance of histological examination of products of conception which helps the pathologist to provide an appropriate diagnosis, thereby the clinician can offer appropriate counseling and follow up to the patient.

Metaplastic Carcinoma of Breast with Extensive Chondroid Differentiation: A Case Report with Review of Literature.

Metaplastic carcinoma of breast (MBC) is a rare and aggressive type of invasive breast cancer. As it encompasses a variety of distinct histopathologic designations, diagnostic challenges abound. We present a case report of metaplastic carcinoma with extensive chondroid differentiation. This case merits presentation because of its rarity and difficulty to diagnose, especially if the tumour is composed mainly of sarcomatous elements. Standard chemotherapy regimes are ineffective against MBC. The prognosis of MBC is poor in comparison to classical invasive breast cancer. Data focusing on MBC is limited due to its rare incidence.

Lymphoepithelioma-like Carcinoma of Endometrium; A Rare Case Report.

Lymphoepithelioma -like carcinomas (LELCs) are tumors with histological features similar to those of lymphoepithelioma of nasopharynx. They have been described in many organs including female genital tract. Their histology is characterized by sheets, nests and cords of large syncytial tumor cells containing round nuclei with prominent nucleoli and dense lymphoplasmacytic infiltrate in the stoma. The association of Epstein-Barr virus (EBV) with LELCs has not been observed in western patients. But a few Asian patients with these tumors in uterine cervix have shown positive association of EBV. Cervical LELCs harbor EBV more frequently than cervical squamous cell carcinomas. These tumors are rarer in endometrium. Only 3 cases have been reported and the association of EBV has not been observed. We present here a rare case of LELC in endometrial polyp from India, who presented with postmenopausal vaginal bleeding. The tumor cells were positive for cytokeratin and EBV Latent membrane protein-1.

Mucinous Cystadenocarcinoma Co-Existing with Mature Cystic Teratoma : A Rare Case Report.

Co-existence of mucinous cystadenocarcinoma with mature cystic teratoma in the same ovary is very rare. We report a case in a 48-year-old female who presented with left abdominal mass. CT scan revealed a heterogeneous enhancing left ovarian mass lesion. Clinical diagnosis of complex ovarian cyst was made, later underwent laparotomy and histologically diagnosed as mucinous cystadenocarcinoma (grade 2) co-existing with benign cystic teratoma, stage Ia (FIGO) of the left ovary. Six months after surgery, the patient is doing well without any recurrence or metastasis. Hence, histopathological examination plays a significant role in accurate diagnosis and management of the patient. So, we should be aware of these rare co-existent tumours and meticulous dissection should be done to look for any synchronous tumours or malignant areas; since management and prognosis will vary significantly depending upon the microscopic type and stage.

Immunohistochemical profile and morphology in triple - negative breast cancers.

BACKGROUND AND PURPOSE: Triple Negative Breast Cancer (TNBC) is defined by a lack of expression of the steroid hormone receptors (oestrogen and progesterone), and the human epidermal growth factor receptor-2 (HER-2). It is characterized by distinct molecular, histological and clinical features. It is a high risk breast cancer that lacks the benefit of a specific therapy. Our study was aimed at pathologically illustrating triple-negative breast carcinoma and at evaluating the expression of the Epidermal Growth Factor Receptor (EGFR) ,cytokeratin 5/6 (CK 5/6) and Ki-67 among triple-negative breast cancer cases. Further, we aimed to probe whether triple-negative phenotype could be a surrogate marker for the basal phenotype and to correlate the expression of the basal markers (CK 5/6 and EGFR) with the clinico-pathological prognostic parameters. METHODS: The expression of EGFR, CK 5/6 and Ki-67 were studied by immunohistochemistry (IHC) in 50 triple-negative breast cancer cases. STATISTICAL ANALYSIS: A statistical analysis was implemented by using the SPSS version 20.0. The Chi-square test was conducted to assess the relationship between the immunohistochemical markers and other variables. The Fischer exact test was used when the expected cell counts were less than 5. RESULTS: The women with triple-negative breast cancer were younger, with the adverse pathological characteristics of a high tumour grade, tumour necrosis, frequent nodal metastases and high proliferation. 37 (74%) of the 50 triple-negative breast carcinomas showed the expression of the basal markers (EGFR and /or CK 5/6). We observed a statistically significant association between the basal marker expression and the presence of tumour necrosis. CONCLUSION: The triple-negative breast cancers in our population harbour adverse pathobiological features and a five marker immunohistochemical panel can be reliably used to define the basal-like cancers. The "Triple-negative" status cannot be used as a surrogate for the "basal marker expression".

Morphological profile and receptor status in breast carcinoma: an institutional study.

CONTEXT: The data on histological and receptor status in breast cancer in an Indian population is limited as receptor status is not routinely carried out for these patients. In the present study, receptor status was analyzed and it was correlated with morphological prognostic parameters. OBJECTIVE: To analyze the morphological prognostic parameters and its correlation with receptor status in Indian women. DESIGN: The sample consisted of 126 specimens of invasive breast cancer received in department of pathology of our institution with teaching hospital attached to it, situated in South Canara district of, Karnataka, South India between year 2009 and 2011. RESULT: Sixty-seven percent of patients were 50 years or younger. Histological types were invasive ductal carcinoma, not otherwise specified (58.7%), and overall (15.9%) were grade 3. Estrogen receptor was positive in 36.5%, HER/neu was overexpressed in only three cases; 50.0% were "triple" negative (estrogen receptor, progesterone receptor, HER/neu negative). Estrogen receptor (ER) and progesterone receptor (PR) positivity decreased with increase in tumor grade. There was significant association between tumor size and ER positivity. CONCLUSIONS: Breast carcinoma in our population presents at younger age than Western population. Our results showed very high proportion of triple-negative breast cancers. The tumor size and grade is related to expression of only ER. The findings suggest that women in our population more often have histologically aggressive breast carcinoma at young age, likely to be less susceptible to conventional hormonal and targeted antibody treatment. Detecting and treating this increasing important cause of mortality will be an enormous challenge.

Rare case of extraskeletal Ewings sarcoma of the sinonasal tract.

Ewings sarcoma (ES) and primitive neuroectodermal tumor are closely related family of small round cell tumors seen in childhood and adolescence. The incidence of these tumors occurring in the head and neck region is just 2-7%. Mandible and maxilla are the most common sites, whereas involvement of the sinonasal tract is very rare. We report a case of extraskeletal ES of the sinonasal tract in a 29-year-old female who presented with nasal obstruction and epistaxis. The patient was treated with 14 cycles of chemotherapy, combined with surgery and radiotherapy with complete recovery. We present this case due to its rarity, to analyze the clinical, histopathological and immunohistochemical findings, so as to differentiate from other small round cell tumors of the sinonasal tract for appropriate treatment.

Uncommon manifestations of Endocervical Malignant Mixed Mullerian Tumor with Incidental Bilateral Fallopian Tube Carcinoma.

A 43-year-old perimenopausal lady presented with bleeding per vagina and lower abdominal pain. On evaluation, she had cervical polyp, which expelled spontaneously during the per speculum examination. Histopathology revealed malignant mixed Mullerian tumor. Extended hysterectomy with salphingo oophorectomy was carried out, which showed bilateral fallopian tube carcinoma and leiomyoma uterus. The patient was treated with carboplatin regime and found to be disease-free for 1 year. This case presented because of a rare combination of the lesions.

Epignathus with fetiform features.

Epignathus is an extremely rare oropharyngeal teratoma that commonly arises from the palate, leading to a high mortality (80-100%) due to airway obstruction in the neonatal period. We present a case of epignathus immature teratoma with fetiform features, originating from basisphenoid in a 28-week preterm male baby, who succumbed to death immediately after birth. Since epignathus is a life-threatening condition at the time of delivery, a prenatal diagnosis is essential to coordinate the treatment and appropriate management by securing the airway, either by endotracheal intubation or tracheostomy followed by complete resection of the tumor.

Unusual cause of childhood anemia: Imerslund Grasbeck syndrome.

Imerslund Grasbeck syndrome (IGS) is a rare autosomal recessive childhood disorder characterized by selective Vitamin (vit) B 12 malabsorption with asymptomatic proteinuria without any structural renal pathology. The patients stay healthy for decades with life-long parenteral vit B12. We report a case of young female who presented with pancytopenia and proteinuria, evaluated in local hospitals as chronic hemolytic anemia (autoimmune cause), finally diagnosed as IGS on complete evaluation. She was treated with injectable vit B12 (1000 µg cyanocobalalmin) and showed drastic recovery. IGS should be considered in patients with megaloblastic anemia not responding to oral vit B12 and associated proteinuria.