Disseminated malignant phyllodes: Presentation after a decade.

Phyllodes tumors are rare biphasic fibroepithelial lesions of the breast and account for 0.3%-0.5% of primary breast tumors. Malignant phyllodes tumor has a 10%-26% risk of distant metastasis. The most common site of metastasis is lungs followed by bone and soft tissue. This is a rare case of a 42-year-old female with a previous history of malignant phyllodes tumor breast. She presented after 10 years with metastases to multiple sites including lung, abdominal wall, retroperitoneum, bone, and brain. These tumors have a poor overall survival. Accurate diagnosis and aggressive management of malignant phyllodes tumors can help in effective treatment at diagnosis and for close follow-up of the patients.

Activation of oncogenic signaling kinase PAK1 by ionising radiation confers an aggressive phenotype in head and neck squamous cell carcinoma.

Head and neck squamous cancers are very aggressive tumors often diagnosed in late stages with poor prognosis. HNSCCs are usually treated by a course of radiation (IR) therapy and followed by surgery. These treatment regimens fail to bring a complete response. Molecular signatures in tumors are attributed to this response and an improved understanding of the signaling events could offer new avenues for therapy. Here, we show that P21 activated kinase-1 (PAK1) - an oncogenic signaling serine/threonine kinase, is activated upon exposure to IR and this leads to an accelerated tumorigenic character in HNSCC cells. Our results show that PAK1 is highly expressed in HNSCC cell lines, as compared to normal buccal mucosa cells and when HNSCC cells were exposed to IR, they show activated PAK1 and an aggressive phenotype as determined by in vitro functional assays. PAK1 levels were elevated in HNSCC as compared to adjacent normal oral tissues and our results also show convincing evidence of activated PAK1 in patient tumor samples of post- IR treatment as compared to pre-IR treatment and is associated with poor survival. Pak1 Knockout (KO) clones in HNSCC cells showed that they were more sensitive to IR as compared to wild type (wt) cells. This altered sensitivity to IR was attributed to enhanced DNA damage response modulated by PAK1 in cells. Overall, our results suggest that PAK1 expression in HNSCC could be a critical determinant in IR therapy response and silencing PAK1 is likely to be a treatment modality to improve clinical outcomes.

Epithelioid leiomyosarcoma: An unusual presentation.

Uterine mesenchymal tumors are a heterogeneous group of neoplasms that can be diagnostically challenging. Thorough investigations and histopathological findings are highly significant to arrive at the correct diagnosis, thus ensuring appropriate and prompt treatment to the patient. Leiomyosarcoma (LMS) is an uncommon uterine malignancy, which arises from the smooth muscle of the uterine wall. They usually present in postmenopausal women with abnormal uterine bleeding. It follows an aggressive clinical course with an extremely poor prognosis. Surgical management followed by adjuvant chemotherapy is usually the treatment for such cases. Here, we report the case of a 57-year-old menopausal female who presented with a large abdominal swelling that was seen infiltrating the adjacent structures. On resection and histopathological evaluation, a diagnosis of epithelioid LMS was made, which was confirmed by immunohistochemistry.

Orbital leiomyoma presenting as inverse globe retraction syndrome: a unique presentation of a rare disease.

Inverse globe retraction syndrome is a rare ocular motility disorder characterized by limited abduction, with globe retraction and up- or downshoots on attempted abduction, differentiating it from globe retraction due to Duane retraction syndrome, seen on attempted adduction. It can be congenital or acquired. We report the case of a 3-year-old girl who presented with classical features of inverse globe retraction syndrome secondary to an underlying orbital tumor involving the medial rectus muscle. Incisional biopsy confirmed the diagnosis of a leiomyoma. At 10 months' follow-up, vision, ocular alignment, and ocular motility had improved.

Utility of immunohistochemical expression of E-cadherin in colorectal carcinoma.

Introduction: Reduced expression of E-cadherin, an intercellular junction protein, is associated with differentiation and metastasis of multiple cancers, including colorectal cancer. Aim: To investigate the utility of the immunohistochemistry of E-cadherin as a prognostic marker for colorectal cancer (CRC). Material and methods: Immunohistochemical analysis for E-cadherin was performed on 100 paraffin blocks retrieved from resected specimens of CRC patients. The collected data were statistically analysed. Results: Among the 100 patients, men comprised 58% and the majority had tumour size of 5-10 cm (55%). Grade II CRC was more common (74%) than grade I and III (13% each). The correlation of E-cadherin expression with lymph node involvement was statistically significant, as revealed by p-value < 0.01, with about 27% in N1 and 13% in N2 stage. E-cadherin expression was significantly correlated with tumour differentiation pattern (p < 0.01), wherein out of 13 poorly differentiated carcinomas, 38.5% and 30.5% of samples showed negative and weak E-cadherin staining, respectively. Conclusions: Furthermore, a shift from membranous E-cadherin staining in normal cells to cytoplasmic and mixed staining was observed in cancer cells. The study indicates that immunohistochemical E-cadherin expression has prognostic value, as revealed by its loss of expression in poorly differentiated cells and lymph node metastasis.

Imaging and pathological discordance amongst the plethora of breast lesions in breast biopsies.

INTRODUCTION: Imaging-guided breast tissue biopsy has become an acceptable alternative to open surgical biopsy for nonpalpable breast lesions. Discussion of abnormal results of the correlation between imaging and pathological findings can be very challenging as it can assist in decision-making with regard to the further treatment options by arriving at a comprehensive diagnosis. MATERIALS AND METHODS: This was a retrospective study. Radiological data from imaging-guided breast biopsies of 500 patients during a 6-year period was collected and classified by a specialist radiologist as per the BI-RADS format. Histopathology reports were studied and discordance analyzed. RESULTS: A total of 500 cases were reviewed. Approximately 33% (168) cases fell into the BI-RADS 3 category, 24.4% (122) into the BI-RADS 4, and 37% (187) into BI-RADS 5 categories. Approximately 50% (n = 250) cases were benign, 2.6% (13) belonged to the high-risk category, and 47.4% (237) were malignant. The number of discordant cases was 12 (2.4%), mostly due to technical factors. Sensitivity of biopsies to detect malignancy was 85%, specificity was 96%, and accuracy of biopsy in diagnosing cancer was 90%. DISCUSSION: The "triple assessment" is the most sensitive method for detecting early breast cancer. An effective communication pathway must be established between a clinician, radiologist, and pathologist for surgical excision in discordance as it carries a high prevalence of carcinoma in these lesions. CONCLUSION: In discordant cases, either due to abnormal results of imaging or of abnormal pathological findings, the final decision is based on two concordant findings, out of the three parameters. This involves a multidisciplinary breast conference and an active participation by the pathologist.

Inflammation-induced PELP1 expression promotes tumorigenesis by activating GM-CSF paracrine secretion in the tumor microenvironment.

The inflammatory tumor microenvironment has been implicated as a major player fueling tumor progression and an enabling characteristic of cancer, proline, glutamic acid, and leucine-rich protein 1 (PELP1) is a novel nuclear receptor coregulator that signals across diverse signaling networks, and its expression is altered in several cancers. However, investigations to find the role of PELP1 in inflammation-driven oncogenesis are limited. Molecular studies here, utilizing macrophage cell lines and animal models upon stimulation with lipopolysaccharide (LPS) or necrotic cells, showed that PELP1 is an inflammation-inducible gene. Studies on the PELP1 promoter and its mutant identified potential binding of c-Rel, an NF-κB transcription factor subunit, to PELP1 promoter upon LPS stimulation in macrophages. Recruitment of c-Rel onto the PELP1 promoter was validated by chromatin immunoprecipitation, further confirming LPS mediated PELP1 expression through c-Rel-specific transcriptional regulation. Macrophages that overexpress PELP1 induces granulocyte-macrophage colony-stimulating factor secretion, which mediates cancer progression in a paracrine manner. Results from preclinical studies with normal-inflammatory-tumor progression models demonstrated a progressive increase in the PELP1 expression, supporting this link between inflammation and cancer. In addition, animal studies demonstrated the connection of PELP1 in inflammation-directed cancer progression. Taken together, our findings provide the first report on c-Rel-specific transcriptional regulation of PELP1 in inflammation and possible granulocyte-macrophage colony-stimulating factor-mediated transformation potential of activated macrophages on epithelial cells in the inflammatory tumor microenvironment, reiterating the link between PELP1 and inflammation-induced oncogenesis. Understanding the regulatory mechanisms of PELP1 may help in designing better therapeutics to cure various inflammation-associated malignancies.

Isolated ureteral extrauterine endometrial stromal sarcoma: an unusual presentation.

Extrauterine endometrial stromal sarcomas (EUESSs) are rare tumours occurring without primary uterine involvement. They are classified as primary or secondary, depending on uterine involvement by stromal sarcomas. A 56-year-old woman who earlier underwent bilateral modified radical mastectomy for adenocarcinoma and total abdominal hysterectomy for endometrial stromal sarcoma, followed by tamoxifen therapy, presented with left loin pain. On evaluation, she had a left renal calculus with hydroureteronephrosis. Before percutaneous nephrolithotripsy, ureteroscopy revealed a polypoidal mass that was diagnosed as EUESS. The mass arose primarily within the ureteral lumen, with periureteric tissue uninvolved. She underwent left radical nephroureterectomy with adjuvant hormonal treatment. This is probably the first case of EUESS arising de novo from within the ureteral lumen without endometriosis, to be reported in medical literature. Immunohistochemistry facilitates earlier diagnosis. Cytoreductive surgery is the definitive treatment and multidisciplinary approach helps in overall survival of the patient.

Molecular dysregulations underlying the pathogenesis of endometriosis.

Endometriosis is a crippling disease characterized by the presence of endometrium-like tissue or scar outside the uterine cavity, commonly confined to the peritoneal and serosal surfaces of the pelvic organs. 10-15% of women in reproductive age are estimated to be affected by endometriosis. Most of these patients present with infertility and suffer from pelvic pain. The benign disease rarely progresses to malignancy. Regardless of its high prevalence, the pathogenesis of the disease is not fully understood. Treatment options for endometriosis are limited and are often based on a symptomatic approach. The unavailability of proper diagnostic approaches, fewer therapeutic options, and sparse understanding of molecular alterations are responsible for the continued disease burden. Exploring the molecular elements causing the pathogenesis of endometriosis may lead to a number of breakthroughs in the treatment of the illness, such as the discovery of new biomarkers for diagnosis and therapeutic targets that can be a guide to better prognosis and reduced recurrence. The goal of this review is to provide the reader a critical understanding of the disease by summarizing the genetic, immunological, hormonal, and epigenetic deregulations that support the molecular basis for development of endometriotic cyst, with a special focus on the study models needed to analyze these changes in the endometriotic microenvironment.

Androgen Receptor Expression in Hypospadias.

INTRODUCTION: The exact mechanism behind the development of hypospadias is unclear. Research studies on androgen receptor (AR) expression are controversial with results stating all possible outcomes - AR elevated, similar, or reduced when compared to normal. AIMS: The aim is to study the AR expression and hormone levels in hypospadias patients and compare them with children having normal genitalia. METHODS: Group 1 (controls) involved patients who underwent circumcision for phimosis while Group 2 involved hypospadias patients who did not receive any preoperative testosterone. Preoperative hormonal assay included luteinizing hormone, follicle-stimulating hormone, and free testosterone levels in all the patients. The foreskin specimen was analyzed for AR expression using immunohistochemistry (anti-AR antibody PathnSitu, clone R441, 1/100 dilution). AR staining was expressed as H score. The H score was calculated by multiplying the intensity of staining and the percentage of stained cells showing cytoplasmic positivity at high power (×40). RESULTS: There were 27 patients in Group 1 while 16 in Group 2 (distal 10; proximal 6).There was no significant difference in the age distribution. The mean H score was significantly higher (189.5) in hypospadias patients compared to controls (97.5) and was significantly higher in proximal (220) compared to distal (159) hypospadias. There was no significant difference in hormone levels between groups. CONCLUSION: AR expression was significantly elevated in hypospadias patients. It was higher in proximal compared to distal hypospadias, probably due to end-organ overexpression. Further larger trials are likely to through light into this controversial subject.

Immunohistochemical expression of polo-like kinase 1 in oral squamous cell carcinoma and oral submucous fibrosis.

CONTEXT: Polo-like kinase 1 (PLK1) is a critical molecule in the proliferation of several human cancers. Overexpression of PLK1 has been correlated with cancer cell proliferation and lower overall survival rates. Although PLK1 has been studied in various tumors, information regarding its expression in oral cancer and precancer is limited. Aims: This study is aimed at evaluating the expression of PLK1 in a potentially malignant and malignant disorder of the oral cavity, namely, oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC), respectively, using the immunohistochemistry technique. It also intended to evaluate the association of the various histological grades of OSCC with the intensity of PLK1 expression. SUBJECTS AND METHODS: Thirty OSMF, thirty OSCC tissues, and thirty control tissues were obtained, and the expression of PLK1 was detected by immunohistochemistry using rabbit antihuman PLK1 polyclonal antibodies (Abcam Ab47867). The association between staining intensity and histological grade of OSCC was evaluated. STATISTICAL ANALYSIS USED: Using SPSS 20 version, a test for proportions, nonparametric Chi-square/correlation analysis was used to compare differences in proportions of categorical variables of interest between groups. Results: PLK1 was positively expressed in 27 (90%) OSCC tissues. OSMF showed no detectable staining in 27 (90%) tissues and positive staining in 3 (10%) tissues. PLK1 showed no staining (0%) in normal tissues. Statistically significant associations were not found between staining intensity and histological grade of OSCC. CONCLUSIONS: PLK1 could be a promising progression marker for OSCC. Therapeutically, targeting PLK1 may be a new approach to fight oral cancer.

Paediatric Peripheral Primitive Neuroectodermal Tumour - A Clinico-Pathological Study from Southern India.

INTRODUCTION: Primitive Neuroectodermal Tumour (PNET)/Ewing Sarcomas (ES) are aggressive childhood malignancies with neuroectodermal differentiation. AIM: To study the clinical presentation, morphology, Immun-ohistochemistry (IHC), management and outcome of all the cases of paediatric pPNET/ES reported in our tertiary care centre over a period of six years. MATERIALS AND METHODS: This was a retrospective study conducted at Sri Ramachandra Medical College and Research Institute, Chennai, India. All biopsy proven cases of peripheral PNET/ES, in patients less than 18 years of age for a period of six years were included in this study. The corresponding clinical details regarding initial presentation, treatment and follow up were retrieved from the case files and analysed. Survival rate was calculated and Kaplan-Meier survival curve was plotted. RESULTS: We describe eleven cases of paediatric peripheral PNET/ES. The mean age at presentation was 94.08 (±58.27) months with a male/female ratio of 1.2:1. About 27.3% cases, all male with a mean age of 140 months at presentation, had distant metastasis during initial diagnosis. Biopsy showed small round blue cell morphology on light microscopy. IHC revealed strong membranous staining for CD99 in all cases. All children were treated with neo-adjuvant chemotherapy and then surgery, followed by radiotherapy if indicated. The cases were followed up for a mean duration of 20.82 months (ranging from one to 66 months). Nine children are doing well on follow up (81.8% survival rate). Two cases with metastasis at initial presentation died. Patients with metastatic disease exhibited a mean duration of survival of 9.66 (±7.24) months and those with localized disease exhibited a mean duration of survival of 25 (±22.88) months. CONCLUSION: Metastasis at diagnosis is the single most important factor affecting prognosis. This was reflected in the present study where cases with metastasis exhibited a short mean duration of survival when compared to localized disease. It is likely that many cases of PNET/ES were not accurately identified in the past as IHC plays a vital role in the diagnosis of these small round blue cell tumours. IHC in adjunct with molecular studies has improved diagnostic accuracy. Multidisciplinary management and good supportive care when the lesion is localized has lead to improved survival.

Sclerosing Pneumocytoma of the Lung: A Case Report.

Pulmonary Sclerosing Pneumocytoma (PSP) is a rare tumour of the lung and is always benign. Diagnosis is made incidentally following chest X-ray or chest CT scan performed for other clinical conditions. We report a case of PSP in a seven-year-old girl who got admitted for evaluation of an anterior mediastinal mass. Clinically, thought of teratoma or other germ cell tumour the mass was excised and sent for histopathological examination. Grossly, we received a pneumonectomy specimen measuring 13x11x8 cm with a nodular firm grey white lesion in the medial aspect of lower and middle lobe measuring 7.5x5.5x5 cm. Macroscopically, pleura was involved and adherent to the lung. Microscopy showed, an ill-defined lesion in the lung with extensive fibrosis and lymphoplasmacytic infiltrate. The lesion was composed of round to oval cells with ill defined cell border, moderate eosinophilic cytoplasm and bland nuclei. A panel of Immunohistochemical (IHC) markers was performed and the lesional cells were positive for Epithelial Membrane Antigen (EMA) and Thyroid Transcription Factor-1 (TTF-1). The prognosis after surgical resection is good and the patient is doing well.

Protective role of apigenin on rotenone induced rat model of Parkinson's disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra which is associated with oxidative stress, neuroinflammation and apoptosis. Apigenin (AGN), a non-mutagenic flavone found in fruits and vegetables, exhibits a variety of biological effects including anti-apoptotic, anti-inflammatory, and free radical scavenging activities. The current study was aimed to investigate the neuroprotective effects and molecular mechanisms of AGN in a rat model of PD induced by rotenone (ROT). Unilateral stereotaxic intranigral infusion of ROT caused the loss of tyrosine hydroxylase (TH) immunoreactivity in striatum and substantia nigra. AGN treatment (10 and 20 mg/kg, i.p.) showed a significant improvement in behavioral, biochemical and mitochondrial enzyme activities as compared to ROT exposed rats. The mRNA expression of inflammatory markers and neurotrophic factors was quantified by reverse transcriptase polymerase chain reaction (RT-PCR). Administration of AGN significantly attenuated the upregulation of NF-κB gene expression in ROT induced group and prevented the neuroinflammation in substantia nigra pars compacta (SNpc). Further, AGN inhibited the release of pro-inflammatory cytokines TNF- α, IL-6 and pro-inflammatory enzyme iNOS-1 induced by ROT. Additionally, AGN prevents the reduction of neurotrophic factors BDNF and GDNF mRNA expression in ROT lesioned rats. Immunoblot results illustrated that AGN treatment downregulated α-synuclein aggregation and upregulated the TH protein expression as well as dopamine D2 receptor (D2R) expression in ROT lesioned rats. Thus, the present findings collectively suggest that AGN exerts its neuroprotection in ROT model of PD and may act as an effective agent for treatment of PD.

Comparative Study on the Estimation of Estrous Cycle in Mice by Visual and Vaginal Lavage Method.

INTRODUCTION: Evaluation of estrous cycle in laboratory animals can be a useful measure of the integrity of hypothalamic-pituitary-ovarian reproductive axis. Assessment of vaginal cytology is crucial to assess the milieu and compare the endocrine status of animals among the experimental groups. AIM: The present study was attempted to compare the estimation of estrous cycle by visual method and non invasive vaginal lavage method. MATERIALS AND METHODS: Sixty healthy female swiss albino mice were used for the present study. The appearance of the vagina with respect to the opening of vagina, vaginal swellings were observed. Non-invasive method was used in vaginal lavage method in which nucleated epithelial cells, cornified squamous epithelial cells and leucocytes present in vaginal smears were used to identify the estrous stages. RESULTS: The estimation of estrous cycle by visual method coincides with the vaginal lavage method. In Vaginal lavage method, the accurate proportion of cells and the transition phases can be evaluated. CONCLUSION: The non-invasive method reduces the risk of pseudo -pregnancy and mechanical trauma. Though, visual method is quick and reliable, for accurate estimation of the stage of the estrous, non-invasive vaginal lavage method is ideal.

Mucinous Cystadenocarcinoma in a Horse Shoe Kidney Masquerading as Giant Hydronephrosis - A Case Report: Diagnostic Challenges, Lessons Learnt and Review of Literature.

Primary epithelial tumour of the renal pelvis is a rare entity. So far, very few cases are reported in literature. Of these, mucin secreting adenocarcinomas are distinctly rare. However, mucinous cystadenocarcinoma, that too arising in a horse shoe kidney is extremely rare to be reported. Mucinous cystadenomas and carcinomas arising from the renal pelvis are regarded to be secondary to a metaplastic change in the urothelium. Here, we present a case of a 51-year-old male, who complained of abdominal pain, palpable abdominal mass, haematuria along with passage of mucoid material in the urine, with a very poorly functioning kidney. A pre-operative diagnosis of horse shoe kidney with pelvi ureteric junction obstruction and a poorly functioning kidney was made. Intraoperative findings and frozen section biopsy were suggestive of mucin secreting cystic mass and a right heminephrectomy was done. The final histopathology was suggestive of mucinous cystadenocarcinoma of the renal pelvis of the right moiety. This case is presented for its rarity, diagnostic challenges faced and the lessons learnt, stressing on the need for having a high index of clinical suspicion in making such diagnosis.

Immunolocalization of heme oxygenase-1 in periodontal diseases.

CONTEXT: Chronic periodontitis is an inflammatory condition of supporting tissues initiated by organisms in dental plaque. The reactive oxygen species and free radicals mediate connective tissue destruction in periodontitis. In order to counteract the free radical mediated tissue damage, numerous antioxidant mechanisms exist within the host. One such system is heme oxygenase enzymes. Heme oxygenase is the key enzyme involved in catabolism of heme. It cleaves the heme molecule to yield equimolar amounts of biliverdin, carbon monoxide, and iron. These end products act as important scavengers of reactive oxygen metabolites. Increased heme oxygenase expression has been identified in inflammatory condition, such as pancreatitis, diabetes, nephritis, and atherosclerosis. Since chronic periodontitis is one such inflammatory condition, we assessed the expression of heme oxygenase-1, in smokers and periodontitis group using immunohistochemistry technique. AIMS: The aim of this study is to compare the expression of heme oxygenase-1 in patients with healthy periodontium, periodontitis and smokers. MATERIALS AND METHODS: Gingival tissue samples were taken from 30 patients, who were divided into three groups healthy controls (n = 10), chronic periodontitis (n = 10), and smokers with chronic periodontitis (n = 10). All the samples were subjected to immunohistochemical staining using the antiheme oxygenase-1 antibody and were tested for efficiency by staining a positive control (prostate cancer tissue sections) and a negative control. The results were tabulated and analyzed. RESULTS: Our results showed increased expression of heme oxygenase-1 in the gingival tissue samples taken from smokers compared with periodontitis and healthy tissue. CONCLUSION: The results of our study is an increasing evidence of involvement of antioxidant enzymes like heme oxygenase-1 in periodontal inflammation and their implication for treatment of chronic periodontitis.

Malignant melanoma of the external auditory canal.

Primary malignant melanoma of the external auditory canal is rarely reported. Malignant melanoma of the ear is estimated to occur in 1-4% of all skin melanomas and about 7-20% of melanomas of the head and neck region. The pathophysiology of these tumours is different from other skin lesions because of their anatomical and functional characteristics. The case presented is of a 11 year old female child with malignant melanoma of the external auditory canal confined to the right side, who initially presented with right ear pain, bleeding, post auricular swelling and also a mass in the external auditory canal which was thought to be an aural polyp in the right ear. Excision of the tumour was accomplished by a radical mastoidectomy. It was confirmed to be malignant melanoma after histopathological examination and Immunohistochemistry. Despite all efforts, the patient succumbed to the disease after receiving three cycles of chemotherapy. Even though this malignancy is rarely found in the external auditory canal, it should be expanded into the differential diagnosis of an aural polyp and a post aural abscess. The incidence, symptoms, investigations, treatment and prognosis of malignant melanoma of the external auditory canal is discussed in this article.