Alka Bhatia

Malignant atypical cell in urine cytology: a diagnostic dilemma

Aims The aim of this study was to find out the characteristic morphology of malignant atypical cells which were missed on routine cytology of urine. Materials and methods In this retrospective study, we examined detailed cytomorphology of 18 cases of atypical urinary cytology which were missed on routine examination and were further proved on histopathology as transitional cell carcinoma (TCC) of bladder. The cytological features of these cases were compared with 10 cases of benign urine samples. Results There were 11 cases of high grade TCC and 7 cases of low grade TCC on histopathology of the atypical urine samples. Necrosis in the background and necrosed papillae were mostly seen in malignant atypical cells. The comet cells and cells with India ink nuclei (single cells with deep black structure-less nuclei) were only observed in malignant atypical cells. The most consistent features in malignant atypical cells were: i) high nuclear and cytoplasmic (N/C) ratio ii) nuclear pleomorphism iii) nuclear margin irregularity iv) hyperchromasia and v) chromatin abnormalities Conclusion The present study emphasizes that nuclear features such as high N/C ratio, hyperchromasia and chromatin abnormalities are particularly useful for assessing the malignant atypical cells. Other cytological features such as comet cells and cells with India ink nuclei are also helpful for diagnosis but have limited value because they are less frequently seen.

Cellular and molecular mechanisms in cancer immune escape: a comprehensive review

Immune escape is the final phase of cancer immunoediting process wherein cancer modulates our immune system to escape from being destroyed by it. Many cellular and molecular events govern the cancer’s evasion of host immune response. The tumor undergoes continuous remodeling at the genetic, epigenetic and metabolic level to acquire resistance to apoptosis. At the same time, it effectively modifies all the components of the host’s immunome so as to escape from its antitumor effects. Moreover, it induces accumulation of suppressive cells like Treg and myeloid derived suppressor cells and factors which also enable it to elude the immune system. Recent research in this area helps in defining the role of newer players like miRNAs and exosomes in immune escape. The immunotherapeutic approaches developed to target the escape phase appear quite promising; however, the quest for a perfect therapeutic agent that can achieve maximum cure with minimal toxicity continues.

Cancer cell micronucleus: an update on clinical and diagnostic applications

Micronucleus (MN) is the small nucleus that forms whenever a chromosome or its fragment is not incorporated into one of the daughter nuclei during cell division. Any form of genotoxic stress due to extraneous or internal factors leads to formation of a MN, which serves as an indicator of chromosomal instability. Chromosomal damage and formation of MN are believed to play a significant role in the pathogenesis of many malignancies. Studies have shown that MN assay can be used as a tool for risk prediction, screening, diagnosis, prognosis and as a treatment‐response indicator in cancers. With the advancements in technology, greater details are becoming available regarding the molecular events in carcinogenesis. The micronuclei (MNi) in the cancer cells are now being used as tools to understand the pathogenetics of the malignancies. However, despite large number of studies on MNi in lymphocytes or exfoliated cells of cancer patients, the data regarding a cancer cell MN remain scarce. This review article tries to unleash some of the mysteries related to the formation of MN inside the cancer cell. Also, it discusses the possible effects and the events post MN formation in the cancer cell.

Papillary glioneuronal tumor: a new entity awaiting inclusion in WHO classification

Papillary glioneuronal tumor (PGNT) is a recently described lesion of the brain, which is still not included as a separate entity in WHO classification. To date 32 cases of PGNT have been reported in the world literature. We report the 33rd case, a 41-year-old male who presented with pain in the nape of the neck. MRI showed a large, predominantly solid mass involving the cerebral parenchyma of the left temporal and parieto-occipital lobes with extension across the midline. Histologically, it was a mixture of glial and neuronal components. Architecturally, the tumor was notable for its pseudopapillary pattern with hyalinized vessels. PGNT is considered as a low grade neoplasm and surgical excision has been curative in most of the cases. More cases of PGNT need to be reported as they may add further knowledge about its biologic behavior and allow its recognition and classification.

Renal cell carcinoma metastasizing to duodenum: a rare occurrence

BackgroundDuodenal metastasis is rare in renal cell carcinoma (RCC) and early detection, especially in case of a solitary mass, helps in planning further therapy.Case presentationWe present the case report of a 55 year old male with duodenal metastasis of RCC. This patient presented with jaundice and abdominal lump one year after nephrectomy. On upper gastrointestinal endoscopy a submucosal mass lesion was noted in the duodenum, the biopsy of which revealed metastasis.ConclusionIn a nephrectomized patient presenting with jaundice and an abdominal mass, the possibility of metastasis should be suspected and a complete evaluation, especially endoscopic examination followed by biopsy, should be carried out.

Cancer-Immune Equilibrium: Questions Unanswered

Cancer-immune (CI) equilibrium constitutes an important component of the cancer immunoediting theory. It is defined as a period during which our immune system and cancer live in harmony in the body. The immune system, though not able to completely eliminate the cancer, doesn’t allow it to progress or metastasize further. Mechanisms of this phase are poorly understood because this phase is difficult to identify even by the most modern detection methods. Till now, the work done on the equilibrium phase of cancer, suggests promising improvements in cancer therapy if the disease could be withheld in this phase. However, there are many queries which remain to be addressed about this interesting yet unresolved phase of cancer immunity.

Dabska tumor (Endovascular papillary angioendothelioma) of testis: a case report with brief review of literature

The Dabska tumor also known as Endovascular papillary angioendothelioma is a rare type of hemangioendothelioma characterized by intraluminal papillary endothelial structures. Most of these are superficial in location but occurrence in deeper tissues is also known. We describe case report of testicular Dabska tumor in a child presenting as inguinal hernia. To the best of our knowledge this is the first case report describing the occurrence of this rare entity in testis.

Liver pathology in collagen vascular disorders highlighting the vascular changes within portal tracts

BACKGROUND Collagen vascular disorders (CVDs) are autoimmune disorders with multisystem involvement. Clinical liver involvement is not a characteristic feature though histological involvement could be frequent. Liver disease in CVDs could be the consequence of various factors. AIM The aim was to analyze the histological spectrum of liver in collagen vascular disorders (CVDs) at autopsy. MATERIALS AND METHODS Thirty-six autopsy livers negative for hepatitis B or C virus were studied in CVD cases with no known association with chronic liver disease or vascular thrombosis or hematological disorder. Cirrhotic and normal livers were used as controls. The paired t-test, one-way ANOVA, and two-sided Dunnett t-test were used for comparison (< 0.05). None of the control cases showed any abnormal vessels. RESULTS There were 21 systemic lupus erythematosus (SLE), 7 rheumatoid arthritis (RA), 5 systemic sclerosis (SSc), and 3 polyarteritis nodosa (PAN) cases (M:F = 11:25, age range 23-60 years). HISTOLOGY Diffuse nodular regenerative hyperplasia of liver (NRHL) was seen in 10 cases, and 6 (5 SLE and 1 RA) had numerous abnormal thin-walled vessels in intermediate- and small-sized portal tracts with no vascular occlusion or inflammation. Moderate sized portal tracts showed more interface and lobular inflammation. The main portal vein and its major branches were normal. None of these six cases had increased transmainases (P>0.05). Most SLE cases had increased transaminases (P<0.05). No evidence of portal hypertension was seen in all except in one RA. Septicemia is known to be associated with raised transaminases. CONCLUSION A rare pathology of conglomerate of abnormal vessels in intermediate- and small-sized portal system was observed co-existing with NRHL in CVDs. Raised liver enzyme with interface hepatitis in CVD may not necessarily warrant an overlap, as a similar feature could be observed in septicemia.

Urinary-exosomal miR-2909: A novel pathognomonic trait of prostate cancer severity

The global occurrence of prostate cancer with a range of patient outcome has prompted various investigators to explore novel molecular biomarkers that can precisely detect and track this type of cancer severity. Several studies suggest that micro-RNAs have emerged to act as a new largely unexplored class of biomarkers because of their inherent stability, resilience and recruitment into exosomes present in various human body fluids. With this study, we aim to reveal the nature of urinary-exosomal miR-2909 & miR-615-3p recruitment in patients suffering from either prostate cancer (n=90) or bladder cancer (n=60) as compared to that in either prostate disease-control subjects having benign prostate hyperplasia (n=10) or healthy subjects (n=50). Unlike miR-615-3p, the urinary- exosomal miR-2909 recruitment was not only observed conspicuously in subjects having prostate cancer in comparison to bladder cancer but also the extent of urinary exosomal miR-2909 recruitment showed characteristic variation as a function of prostate cancer aggressiveness as compared to that of either urinary- exosomal miR-615-3p level or existing widely recognised serum prostate specifics antigen (PSA) biomarker of this cancer. In summary, we propose that the extent of urinary exosomal miR-2909 recruitment may provide a potential non-invasive candidate diagnostic marker for the detection of prostate cancer and its aggressiveness.

Spontaneously Occurring micronuclei in infiltrating ductal carcinoma of breast: A potential biomarker for aggressive phenotype detection?†

Chromosomal instabilities (CIN) manifesting as structural or numerical alterations in the chromosomes are common in malignancies like breast cancer. Assessment of CIN in breast cancer may help to understand its etiopathogenesis. Micronucleus (MN) scoring and aneuploidy have been used to assess the presence of CIN in lymphocytes of various malignancies in the past. In this study, spontaneously occurring MN were counted in epithelial cells on fine needle aspiration cytology (FNAC) smears from 50 patients with benign and malignant breast lesions. Further, the ploidy status and S‐phase fraction (SPF) of the samples was determined by flow cytometry. All these were then correlated with grades of breast cancer at cytology. Most IDC cases showed variable number of MN (n = 16, MN mean = 9.3), in contrast to the benign lesions (n = 26) where they were consistently absent. Aneuploidy and SPF analysis also showed a significant difference between benign (n = 10, mean DNA index [DI] = 0.96 ± 0.04, mean SPF= 8.07% ± 2.93) and malignant (n = 10, mean DI = 1.5 ± 0.41, mean SPF = 25.05% ± 10.35) lesions. On statistical analysis, a positive correlation was observed between the grades of IDC and presence of aneuploidy and high SPF (P‐values < 0.05); however, the difference between the MN scores of grade 2 and 3 cancers was not significant. The study suggests that MN scoring and aneuploidy may be used to assess the presence of underlying CIN in IDC on FNAC smears. Further, collectively they may be explored for their role as biomarkers for predicting the tumor behavior in the breast cancer patients. Diagn. Cytopathol. 2013;41:296–302.