Presence Of Mitoses Research Articles

Cytomorphology of gastrointestinal stromal tumors and extra-gastrointestinal stromal tumors: A comprehensive morphologic study

Background:The term gastrointestinal stromal tumors (GIST) is used to refer to those mesenchymal neoplasms of the gastrointestinal tract (GIT) which express CD117, a c-kit proto-oncogene protein.Aims:To study the cytological features of GIST and extra-gastrointestinal stromal tumors (EGIST), to correlate them with histology and to determine cytological indicators of malignancy.Materials and Methods:Cytological smears from patients diagnosed as GIST/EGIST on histology were retrieved. From Jan 2000 to July 2010, 26 GIST (13 primary, 12 metastatic, one recurrent) and seven EGIST (5 primary, one metastatic, one recurrent) cytologic samples from 27 patients were identified.Results:The patients included 20 males and 7 females with a mean age of 50.6 years. Tumor sites included stomach (5), duodenum (5), ileum (2), ileocecal (1), rectum (1), liver (9), retroperitoneum (5), mesentery (1), subcutaneous nodule (1), supra-penile lump (1), ascitic (1) and pleural fluids (1). The smears were cellular with cohesive to loosely cohesive thinly spread irregularly outlined cell clusters held together by thin calibre vessels. The tumor cells were mild to moderately pleomorphic, spindle to epithelioid with variable chromatin pattern and variable cytoplasm. Cellular dyscohesion, nuclear pleomorphism, intranuclear pseudoinclusions, prominent nucleoli, mitosis and necrosis were more prominent in malignant, metastatic and recurrent tumors.Conclusions:GISTs show a wide spectrum of cytological features and the presence of mitosis, necrosis and nuclear pleomorphism can help in prediction of malignant behavior. Further, cytology is a very useful screening modality in patients of GIST and EGIST to detect early recurrence and metastasis at follow-up.

Extragnathic odontogenic sinonasal myxoma with mitotic features.

We present the first-ever documented evidence of mitotic figures in a case of sinonasal myxoma diagnosed in a 37 year-old gentleman. A 37 year-old gentleman was referred to the Otolaryngology clinic with left nasal discharge for six months. Preoperative images demonstrated obstruction of the left nasal airway with complete opacification of the left maxillary sinus, obscuration of the osteomeatal complex, as well as expansion and thinning of the medial wall of the maxillary antrum. The patient underwent diagnostic Funtional Endoscopic Sinus Surgery (FESS), therapeutic left Caldwell-Luc antrostomy, and revision FESS following recurrence. The patient was symptom-free at routine follow-up post-op. There has been much debate as to whether the absence of mitotic features in a specimen is absolutely necessary in order to confirm the diagnosis. We postulate that the presence of mitoses is an unusual diagnostic feature in extensive sinonasal myxoma.

Current advances and perspectives in the treatment of advanced melanoma

Melanoma has long been considered as an extremely therapy-resistant tumour. Recent developments in the area of immunotherapy as well as targeted therapy showed rapid development and excellent results. The anti-CTLA-4 antibody ipilimumab, which was approved in the USA and Europe in 2011, was the first substance in melanoma therapy to demonstrate an overall survival benefit. Another approval is expected in Europe for the specific BRAF-inhibitor vemurafenib, which has shown a significant impact on progression-free survival and overall survival in patients with the BRAF(V600E) mutation. In this review the relevant agents in the substance classes of immunomodulatory drugs and small molecules are presented and discussed, and future prospects for combination therapies and developments in melanoma treatment are outlined.

Single versus multiple primary melanomas

In patients with multiple primary melanomas (MPM), mean tumor thickness tends to decrease from the first melanoma to the second melanoma, and prognosis may be improved compared with the prognosis for patients who have a single primary melanoma (SPM). In this study, the authors compared the clinicopathologic features of patients with MPM and SPM to better characterize the differences between these 2 groups and to determine whether or not there is an inherent difference in tumor aggression. In total, 788 patients with melanoma who were enrolled prospectively in the Interdisciplinary Melanoma Cooperative Group database from 2002 to 2008 were studied. Patients with SPM and with MPM were compared with regard to clinical and primary melanoma characteristics. Of 788 patients with melanoma, 61 patients (7.7%) had 2 or more primary melanomas. The incidence of developing a second primary melanoma 1 year and 5 years after initial melanoma diagnosis was 4.1% and 8.7%, respectively, and most of the risk accumulated within the first year. The incidence of MPM was greater in patients aged ≥60 years than in those aged ≤60 years. The absence or presence of mitosis and other tumor characteristics did not differ significantly between patients with SPM and patients with MPM (P = .61). No difference was observed in the presence or absence of mitoses, a marker of tumor proliferation, in SPM and MPM. Because it has been demonstrated that the presence of mitosis is a powerful prognostic marker, the current findings suggested that the tumors behave similarly in patients with SPM and patients with MPM. The authors concluded that differences in tumor thickness and prognosis between SPM and MPM more likely are caused by factors other than tumor biology, such as increased surveillance.

Dural Metastasis of Atypical Extraventricular Neurocytoma with the Codeletion of Chromosomes 1p/19q

Extraventricular neurocytoma (EVN) is a rare neoplasm described in the 2007 World Health Organization classification of tumours of the nervous system. Due to the rarity of the tumour, there is limited literature available. The clinical characteristics, pathological features, biological behaviour and outcome of EVN remain unclear, and there are challenges regarding its diagnosis and management. The present case was a 75-year-old man who had been experiencing slow responses to stimuli for 1 month prior to hospital admission. A diagnosis of atypical EVN was made on the basis of pathology and immunohistochemistry results. Atypical pathological features included vascular proliferation, the presence of mitosis and a high MIB-1 (an antibody against Ki-67) labelling index. The disease recurred 7 months after the initial complete resection and radiation treatment, presenting with dural metastasis and codeletion of chromosomes 1p/19q. The present case history and treatment course are discussed with respect to the literature.

Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma

To assess the frequency and type of oncogenic BRAF mutations in metastatic melanoma and correlate BRAF status with clinicopathologic features and outcome. Consecutive BRAF-tested Australian patients with metastatic melanoma (n = 197) were observed prospectively. A comprehensive range of clinicopathologic variables were correlated with BRAF mutation status, and a survival analysis was conducted. Forty-eight percent of patients had a BRAF mutation; 70 patients (74%) had V600E, 19 (20%) had V600K, and six (6%) had other genotypes. Other than age at diagnosis of distant metastasis (median age, 56 v 63 years for BRAF-mutant v BRAF wild-type patients, respectively; P < .001), there was no significant difference in clinical features of patients with metastatic melanoma by mutation status. Features of the antecedent primary melanoma significantly associated with a BRAF mutation (P < .05) were histopathologic subtype, presence of mitoses, single or occult primary melanoma, truncal location, and age at diagnosis of primary tumor ≤ 50 years. The interval from diagnosis of first-ever melanoma to distant metastasis was not significantly different between BRAF-mutant and BRAF wild-type patients; however, the median survival of patients with newly diagnosed metastatic melanoma was 5.7 months for BRAF-mutant patients not treated with a BRAF inhibitor, 8.5 months for BRAF wild-type patients, and not reached for BRAF-mutant patients treated with a BRAF inhibitor. V600K mutations comprised 20% of BRAF mutations. Characteristics of the antecedent primary melanoma and age at diagnosis differed in BRAF-mutant and BRAF wild-type patients. The presence of mutant BRAF had no impact on the disease-free interval from diagnosis of first-ever melanoma to first distant metastasis; however, it may have impacted survival thereafter.

31. Prognostic importance of the extent of ulceration of clinically localised cutaneous melanoma

Background The presence of ulceration is an adverse prognostic factor in clinically-localised cutaneous primary melanoma (PM). However, whether the extent of ulceration has any prognostic importance remains unclear. We sought to determine the prognostic value of the extent of ulceration categorised as diameter of ulceration and as percentage of invasive melanoma. Methods Clinico-pathological data on patients with PM were collected from the Melanoma Institute Australia database. In patients with ulcerated melanomas, diameter and percentage ulceration (ratio of diameter of ulceration to diameter of invasive melanoma) were identified from the database or measured if slides were available for review. Ulceration was defined as full-thickness loss of epidermis overlying melanoma. The impact of clinico-pathologic parameters and extent of ulceration on survival was analysed. Results Male sex, head/neck anatomical location, increasing Breslow thickness and presence of mitoses were independent predictors of poorer melanoma-specific survival (MSS). Presence of ulceration was an independent predictor of poorer MSS (HR=1.55, 95%CI 1.21-2.00). Patients with tumours ulcerated ≤70% and ≤5 mm had significantly poorer MSS than non-ulcerated melanoma [HR = 1.53, 95%CI 1.07-2.21 and HR=1.39, 95%CI 1.04-1.87, respectively). Compared with all patients with ulcerated melanoma (HR = 1.55) patients with tumours ulcerated >70% or >5 mm had a significantly higher risk of death (HR = 2.20, 95%CI 1.26-3.82 and HR = 2.03, 95%CI 1.37-3.03, respectively). Conclusions Extent of ulceration provides more prognostic information than the mere presence of ulceration, and this has important implications for melanoma patients with regard to prognosis, staging, management and eligibility for clinical trials. We recommend that extent of ulceration be recorded in pathology reports for all ulcerated PMs.

CSF cytology—the ongoing dilemma to distinguish neoplastic and inflammatory lymphocytes

To evaluate different morphological criteria for the distinction between inflammatory and neoplastic lymphocytes in the cerebrospinal fluid (CSF). Forty-two cytospin preparations of CSF from patients with confirmed CSF involvement by aggressive B-cell lymphoma or acute leukemia were compared with 26 samples of inflammatory diseases. CSF cytology was analyzed morphologically for preselected parameters of cell, cytoplasm and nucleic appearance, and the presence of mitoses or apoptoses. None of the evaluated parameters sharply discerns neoplastic and inflammatory changes. However, neoplastic cells were significantly larger. Moreover, irregular shape and pointed borders of the cytoplasm, and deep notches in the nucleus were significantly more frequent in neoplastic than in inflammatory lymphocytes. No single parameter is sufficient to detect neoplastic lymphocytes. Considering a combination of cell size and irregular shape of cell and nucleus, however, may improve the diagnostic accuracy of CSF dissemination by aggressive hematological malignancies.

Clinical outcome and pathologic features associated with NRAS mutation in cutaneous melanoma.

8500 Background: Mutations in NRAS and BRAF are common in cutaneous melanoma leading to constitutive activation of the MAPK pathway controlling cell proliferation. We examined the effect of NRAS mutations on the pathologic features and clinical outcomes in patients with cutaneous melanoma when compared to tumors containing BRAF mutations and those wild-type (WT) for both. Methods: Clinical outcome data was obtained from a prospective cohort study of 251 patients with cutaneous melanoma from Australian melanoma centers. Mutations in exon 2 of NRAS (N61R) and exon 15 of BRAF were detected by high resolution melting and sequence verified. Cox proportional hazards regression was performed to examine the significance of NRAS and BRAF mutations on pathologic features, overall survival (OS), melanoma specific survival (MSS) and disease free survival. Results: 249 patients with a median follow-up of 47 months were available. NRAS mutations were found in 36 (14%) patients, BRAF mutations in 112 (45%) and 101 (41%) were WT. 39 deaths occurred, 28 due to melanoma. Overall survival was similar in the three groups. Compared to WT in univariate analysis, there was shorter MSS in patients with NRAS mutations (HR 2.51; p = 0.05) but no difference in those with mutations in BRAF (HR 0.98; p = 0.96). NRAS mutations were associated with thicker tumors with 75% of tumors > 1 mm thick having mutations in NRAS compared to 40% for BRAF and 34% for WT. NRAS mutations were also associated with increased proliferation rates with 75% of tumors having > 1 mitosis/mm2 containing mutations in NRAS (BRAF 40% WT 55%). Multivariate analysis of MSS identified NRAS mutations as an independent adverse prognostic factor (HR 3.22; p = 0.03) along with site, Breslow thickness and presence of mitosis (p < 0.03). BRAF mutations had no effect on MSS (HR 1.68; p = 0.26). Conclusions: NRAS mutation in cutaneous melanoma is associated with higher rates of tumour proliferation when compared to BRAF and WT melanoma and independently of this, associated with shorter melanoma specific survival. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Novartis, Pfizer

Evaluation of Inverted Papilloma and Squamous Cell Carcinoma by Nasal Contact Endoscopy

Contact endoscopy (CE) was initially described as a method used in the analysis of uterine and vocal folds histology. The first nasal cavity CE studies achieved promising results regarding its use for the differentiation between benign and malignant lesions, considering that biopsy might cause some complications, especially bleeding. This study described and compared the findings of CE on inverted papilloma and nasosinusal squamous cell carcinoma (SCC) and tested the effectiveness of this exam as a noninvasive method for in vivo differentiation between these tumors. The patients included in this study were divided into group A, patients diagnosed with inverted papilloma, and group B, patients diagnosed with SCC. CE results were compared among themselves. CE images were presented to examiners not experienced with the method. Twenty-two patients were examined, 13 in group A and 9 in group B. The main relevant differences in CE findings between those two groups were corkscrew vessels, presence of mitoses, keratinization and nuclear pleomorphism in carcinoma, and vacuolated cells in papilloma. The examiners were capable of defining the diagnosis of these nasal tumors only based on CE images. CE may be a useful noninvasive exam to be used in the in vivo diagnosis of inverted papilloma and nasosinusal SCC, which may enable better preoperative planning.

Melanocytic Tumors of Uncertain Malignant Potential

Several reports demonstrated the difficulties and lack of agreement in the histopathologic diagnosis of particular melanocytic tumors (atypical Spitz tumors, atypical blue nevi, deep penetrating nevi). These lesions are often referred to as "melanocytic tumors of uncertain malignant potential" (MELTUMP). We studied a large number of such tumors to find out whether repeatable histopathologic criteria for distinction of benign from malignant cases exist. Fifty-seven cases of MELTUMP were classified within 3 groups according to behavior as follows: (a) favorable (no evidence of metastatic disease after a follow-up of > or = 5 y), (b) unfavorable (tumor-related death and/or large metastatic deposits in the lymph nodes and/or visceral metastases), (c) borderline (small nodal deposits of tumor cells < or = 0.2 mm). There were no significant differences in tumor thickness and presence or absence of ulceration between the different groups. The only 3 histopathologic criteria that were statistically different between the groups of favorable and unfavorable cases were presence of mitoses, mitoses near the base, and an inflammatory reaction, all of them found more frequently in cases with unfavorable behavior. The major outcome of this study of a series of "MELTUMPs" suggests as a preliminary observation that these lesions as a group exist and that they may be biologically different from conventional melanoma and benign melanocytic nevi. The terminology remains highly controversial, reflecting the uncertainty in classification and interpretation of these atypical melanocytic tumors.

Clear cell adenocarcinoma of the bladder and urethra: cases diffusely mimicking nephrogenic adenoma

Although clear cell adenocarcinoma have been described focally mimicking nephrogenic adenoma, we have identified a subset of clear cell adenocarcinoma that diffusely resembles nephrogenic adenoma (nephrogenic adenoma-like clear cell adenocarcinoma). Twelve classic clear cell adenocarcinomas of the bladder and urethra and 7 nephrogenic adenoma-like clear cell adenocarcinomas were compared to 10 nephrogenic adenomas. Classic clear cell adenocarcinomas and nephrogenic adenoma-like clear cell adenocarcinomas comprised 4 men and 15 women. The following features were seen in classic clear cell adenocarcinomas: nephrogenic adenoma-like clear cell adenocarcinomas: predominantly solid pattern (7/12:0/7), marked nuclear pleomorphism (7/12:1/7), prominent nucleoli (5/12:1/7), clear cytoplasm in 50% or greater of tumor (7/12:0/7), and necrosis (8/12:3/7), although the necrosis in nephrogenic adenoma-like clear cell adenocarcinomas was often focal and intraluminal. Both patterns of clear cell adenocarcinomas showed prominent hobnail features, although more pronounced in nephrogenic adenoma-like clear cell adenocarcinomas. Muscularis propria invasion was seen in 5 of 9 classic clear cell adenocarcinomas and 6 of 6 nephrogenic adenoma-like clear cell adenocarcinomas, where evaluable. Classic clear cell adenocarcinoma was associated with urothelial carcinoma (n = 2) and endometriosis (n = 1). The Ki-67 rate in clear cell adenocarcinomas ranged from 10% to 80% compared with 0% to 5% in nephrogenic adenoma. The following antibodies were not helpful in distinguishing nephrogenic adenoma-like clear cell adenocarcinoma from nephrogenic adenoma: CD10, estrogen receptor, p63, high-molecular-weight cytokeratin, and alpha-methylacyl coenzyme-A racemase. PAX2 expression was more frequent in nephrogenic adenoma (89%) compared to both patterns of clear cell adenocarcinoma (29%-32%). The key features discriminating between nephrogenic adenoma-like clear cell adenocarcinoma and nephrogenic adenoma include occasional clear cells, more prominent pleomorphism especially hyperchromatic enlarged nuclei, and extensive muscular invasion. Presence of mitoses and a high rate of Ki-67 expression in lesions resembling nephrogenic adenoma require clinical correlation, close follow-up, and repeat biopsy with more extensive sampling.

Intracystic papillary carcinoma of the breast in a 21-year old premenopausal Nigerian woman: a case report

We report the case of a 21-year-old Nigerian woman who presented to us with features of intracystic papillary carcinoma, a rare form of breast cancer usually seen in postmenopausal women in their sixth to eighth decades of life. To the best of our knowledge, there has been only one other case report of this lesion occurring in women in their second decade of life.Physical examination showed a well-defined mass, 54 mm in diameter, in the upper proximal quadrant of the right breast close to the areola, histologically composed of monotypic epithelial cells disposed in solid, cystic, and papillary patterns. A diagnosis of intracystic papillary carcinoma was made because of the presence of intracystic arborization of the fibrovascular stroma, a monotonous cell population, the presence of mitoses, and the lack of myoepithelial cells determined by immunohistochemistry using calponin and p63 stains. Estrogen receptor status was positive while progesterone status and HER-2-neu receptor status were negative.The patient has survived for 12 months without any sign of recurrence after the last surgical resection of the tumor.

“Lymphomatous and Leukemic Meningitis – Patterns of Cytomorphology and Value of MRI and Protein Analysis”.

Abstract 5011 IntroductionLymphomatous and leukemic meningitis (LM), although a well known and relatively frequent complication of aggressive lymphoma and leukemia, are still difficult to detect. With cytomorphology, neoplastic lyphocytes are difficult to distinguish from inflammatory lymphocytes. We evaluated here if specific morphological criteria can improve this differentiation. Moreover, we assessed the sensitivity of MRI and protein analysis for the detection of LM in comparison with CSF-cytology. Patients and MethodsTo establish cytomorphological criteria, 42 cytospin preparations of CSF from patients with confirmed CSF involvement by aggressive lymphoma or acute leukemia were compared with 26 samples of inflammatory diseases. CSF cytology was analyzed morphologically for pre-selected parameters of cell, cytoplasm and nucleic appearance and the presence of mitoses or apoptoses. For the comparison of cytology and MRI, 38 patients with leukemic or lymphomatous meningitis were evaluated retrospectively for MRI-signs of neoplastic meningitis and for CSF-protein abnormalities (total protein, oligoclonal bands, lactate, ferritine). Resultsas expected, none of the cytomorphological parameters sharply discerns neoplastic and inflammatory transformation. However, neoplastic cells were significantly larger than inflammatory lymphocytes with a mean of 3.0 as opposed to 1.8 times the size of normal small lymphocytes (p=0.0001). Moreover, irregular shape, pointed borders of the cytoplasm, and deep notches in the nucleus were significantly more often found with neoplastic than with inflammatory lymphocytes.The total cell count was elevated in 68% of cases of lymphomatous meningitis. While cytomorphology could achieve approx. 90% sensitivity for the detection of LM, spinal and/or cranial MRI only detected 71% of cases with normal and 52% with elevated cell counts. Total protein was elevated in 77% of cases, lactate in 55% and ferritine in 48%. Oligoclonal IgG was found in 11% isolated in the CSF and in 18% in CSF and serum identically. Only 3/38 patients (8%) had completely normal CSF cell count and proteins. ConclusionsCSF cytology is more sensitive than MRI for the detection of LM, but application of both methods clearly enhances the sensitivity by approx. 10%. No single cytomorphological parameter is sufficient to detect neoplastic lymphocytes. Considering a combination of cell size and irregular shape of cell and nucleus may improve the diagnostic accuracy of CSF dissemination by aggressive hematological malignancies. DisclosuresStrik:Mundipharma : Consultancy, Honoraria, Research Funding, Speakers Bureau; Essex/Shering-Plough/Merck: Consultancy, Honoraria, Speakers Bureau; Medac: Research Funding.

Epigenetic marks in melanoma

Melanoma is a highly heterogeneous cancer that comes in different flavors (lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma, acral lentiginous/mucosal melanoma and other less common subtypes including malignant cellular blue nevus, desmoplastic melanoma, nevoid melanoma, and animal-type melanoma) and colors (black/bluish or unpigmented). Pathologists have known for many years that melanoma displays notable changes in the nuclear architecture including thick chromatic rims, presence of mitosis, nuclear grooves, and more. It is now evident from other cancers that such changes reflect not only genomic alterations but also non-genomic changes in both the structure of DNA and the structure of chromatin to which the DNA is bound (nucleosomes). Although aberrant gene expression resulting from DNA methylation has been known for many years, genome alterations resulting from histone modifications became evident in the current decade. In prostate and other cancers, some histone marks have clinical diagnostic and/or prognostic value. Here, we review the current data on epigenetic research in melanoma skin cancers, discuss ways to modify the epigenetic landscape of melanoma for inhibiting its growth, and propose strategies for identifying novel melanoma markers.

Expression of c-Myc, neurofibromatosis Type 2, somatostatin receptor 2 and erb-B2 in human meningiomas: relation to grades or histotypes

Meningiomas, which originate from arachnoid cells, represent one of the largest subgroups of intracranial tumors. They are generally benign, but can progress to malignancy. The aim of our study was to determine the expression of 4 genes, c-Myc, neurofibromatosis Type 2 (NF2), somatostatin receptor isoform 2 (sst2) and erb-B2, that have been associated with tumorogenesis or, possibly, with aggressive behavior or recurrence of meningiomas. We measured levels of mRNAs coding for these genes by qRT-PCR in 51 cases and levels ofc-Myc protooncogene and sst2 protein by immunohistochemistry in 26 cases of meningiomas of various grades and histotypes. C-Myc mRNA and protein levels were not grade-related, but validated subdivision of the 36 benign meningiomas into two groups, Groups IA and IB, based on histological and clinical features (Ki-67-proliferative index, absence or presence of mitoses, rate of recurrence and incidence of perilesional edema). In addition to histopathological grading, c-Myc expression may be useful in predicting tumor recurrence in patients with low-grade meningiomas. NF2 mRNA levels and sst2 mRNA and receptor levels were not grade-related, but were histotype-related, with significantly higher levels in the meningothelial subtype than in the fibroblastic subtype. Erb-B2 mRNA levels were not grade- or histotype-related. Furthermore, the high expression of sst2 in meningothelial meningioma suggests the possibility of a different tumorigenesis process in this meningioma subtype and may open perspectives for the diagnosis and therapy of this subtype using somatostatin as an antiproliferative agent.

Indirect evaluation of estrogenic activity post heterotopic ovarian autograft in rats

To morphologically evaluate the estrogenic effect on the uterus and vagina of rats submitted to ovarian autografts. Twenty Wistar EPM-1 adult rats were bilaterally ovariectomized, followed by ovarian transplants in retroperitoneal regions. The animals were divided in four groups of five animals, according to the day of euthanasia: G4, G7, G14 and G21, corresponding to the 4th, 7th, 14th and 21st day after surgery, respectively. Vaginal smears were collected from the first day of surgery until euthanasia day. After that, the vagina and uterus were removed, fixed in 10% formaldehyde and submitted to histological analysis and stained with hematoxiline and eosine. All animals showed estrous cycle changes during the experiment. In 4th day, the uterus showed low action of estrogen with small number of mitosis and eosinophils as well as poor development. On the 7th day, the endometrium was atrophic without mitotic signals and presented a small number of eosinophils. On the 14th and 21th days the histological findings were similar, with the presence of mitosis in the endometrial glands and intense leucocyte infiltration with a large number of eosinophils. Morphometric results showed that the endometrial and myometrial thickness as well as the number of eosinophils presented the highest values during the 14th and 21th days of the evaluation. The 7th day group also presented the lowest eosinophil numbers. Vaginal epithelium features were: 4th and 7th day groups presented non-keratinized stratified epithelium with 5 and 2 cell layers, respectively. The 14th and 21st day groups presented non-keratinized stratified epithelium with 14 and 15 cell layers. Experimental ovarian autografts in the evaluated organs presented maximum estrogen activity after the 21st day of surgery, according to morphological and morphometric data.

Cell Division and Maintenance of Epithelial Integrity in the Deafened Auditory Epithelium

Quiescence is among the hallmarks of the sensory epithelium of the cochlea. When auditory sensory cells (hair cells) degenerate they are not replaced, and therefore hearing loss is permanent. Cochlear hair cells are susceptible to several types of lesions, including aminoglycoside antibiotics. The application of the aminoglycoside neomycin in the inner ear mimics cases of severe hair cell loss and leads to collapse of the cochlear epithelium. We now report that in mature guinea pig cochleae injected with neomycin, the remaining non-sensory cells undergo a robust proliferative response. p27Kip1, an inhibitor of cell cycle in the cochlea, was present in non-dividing cells and absent during mitosis. Dividing cells retained their tight junction complexes and maintained the structural confluence of the auditory epithelium during cell division. The plane of mitosis was invariably parallel to the luminal surface. These results indicate that the flat epithelium of the cochlea can down-regulate p27Kip1 and divide after a severe lesion and suggest that the cell divisions assist in maintaining the epithelial confluence throughout the cochlea. Presence of mitosis in the tissue presents therapeutic opportunities for gene transfer and stem cells therapies.

Papillary glioneuronal tumour: a report of a rare case and review of literature

Amongst the mixed glioneuronal tumours, 'papillary glioneuronal tumour', a new variant, has been described recently. We report a case of papillary glioneuronal tumour in a 4-year-old boy who presented with fever, weakness of left upper and lower limbs and headache for the last 2.5 month. Radiologic examination showed a cystic space-occupying lesion with mural nodule in the right frontal lobe with extension into white matter. Surgical excision of a large cystic mass with small solid nodule was done. Pathological examination revealed a well-circumscribed tumour showing predominantly papillary architecture with focal aggregates of cells in sheets. The papillae were composed of hyalinised blood vessels lined by single to multi-layered cells. The tumour cells showed mild pleomorphism without any necrosis. The individual tumour cells had scant eosinophilic cytoplasm, round to oval hyperchromatic nucleus with occasional mitoses. The tumour cells were immunopositive for glial fibrillary acidic protein, synaptophysin, vimentin, and S-100 protein, but negative for neurofilament, epithelial membrane antigen, cytokeratin and CD34. MIB-1 labelling index was approximately 12% in the highest proliferating areas. In view of subtotal excision of the tumour and high MIB-1 labelling index (LI), the patient was given chemotherapy and he is doing well at 1-year follow-up. This report supports the existence of this rare tumour. Some of its rare clinicopathological features like young age, cyst with mural nodule, presence of mitoses and raised MIB-1 LI need to be documented.

Atypical primary carcinoid tumour of the skin

We present a new case of a primary carcinoid tumour of the skin. The mitotic index (4/10 HPF) warrants classification of this case as atypical. The patient was a 58-year-old woman with a 1-year history of a mass on the scalp. Literature review showed this to be only the seventh case of primary carcinoid tumour of the skin. Importantly, the evolution has been favourable in all seven tumours, with a mean follow-up of 2.5 years for the previous six cases. Although the number of cases is too small to draw definitive conclusions, information to date suggests that this type of tumour can be expected to have a benign behaviour, despite the presence in some cases of criteria suggestive of uncertainty, such as the presence of mitosis.