Electrochemical Oxidative Dearomatization Strategy for Accessing Spiro[4.5]dienones and Derivatives.

Electrochemical dearomatization has been recognized as an attractive tool for the rapid construction of structurally diverse molecules. The designed methodology encompasses an eco-friendly and efficient electrochemical approach to synthesizing spiro[4.5]dienones under mild reaction conditions. Furthermore, detailed mechanistic studies strongly bolster our hypothesis and emphasize the role of HFIP in the mechanism. The protocol is scalable and showcases a broad substrate scope with tolerance toward numerous functional groups. Henceforth, this strategy can be deployed as an alternative and sustainable tool for accessing spiro[4.5]dienones.

Xanthogranulomatous Endometritis with calculus formation in setting of prolapsed uterus.

Xanthogranulomatous inflammation is a rare benign inflammatory lesion characterized by sheets of lipid-laden foamy histiocytes. It has been reported in various organs, mainly the kidney and gall bladder. Xanthogranulomatous endometritis (XGE) is sporadic, with only a few cases reported in the English medical literature. Herein, we report a case of xanthogranulomatous endometritis with the formation of stones in a 50-year-old female patient with a prolapsed uterus. Grossly the endometrium was irregular, and the uterine cavity was filled with a yellow friable material, a polypoid growth, and yellowish stones. The microscopy showed sheets of histiocytes with few preserved endometrial glands. In this case, the xanthogranulomatous inflammation may mimic a clear cell carcinoma involving the endometrium and myometrium. One of the important differential diagnoses is malakoplakia. Immunohistochemistry and special stains are helpful in diagnosis.

Xanthogranulomatous Endometritis with calculus formation in setting of prolapsed uterus

ABSTRACT Xanthogranulomatous inflammation is a rare benign inflammatory lesion characterized by sheets of lipid-laden foamy histiocytes. It has been reported in various organs, mainly the kidney and gall bladder. Xanthogranulomatous endometritis (XGE) is sporadic, with only a few cases reported in the English medical literature. Herein, we report a case of xanthogranulomatous endometritis with the formation of stones in a 50-year-old female patient with a prolapsed uterus. Grossly the endometrium was irregular, and the uterine cavity was filled with a yellow friable material, a polypoid growth, and yellowish stones. The microscopy showed sheets of histiocytes with few preserved endometrial glands. In this case, the xanthogranulomatous inflammation may mimic a clear cell carcinoma involving the endometrium and myometrium. One of the important differential diagnoses is malakoplakia. Immunohistochemistry and special stains are helpful in diagnosis.

Electricity mediated [3+2]-cycloaddition of N-sulfonylcyclopropanes with olefins via N-centered radical intermediates: access to cyclopentane analogs.

An external oxidant free electrochemical strategy is designed towards the ß-scission of strained C-C bonds in cyclopropylamine. Moreover, the mechanistic studies ascertained that the methodology encompasses the N-center radical (NCRs) route and provides access to di- or tri-substituted cyclopentane analogs.

Direct Synthesis of Paracetamol via Site-Selective Electrochemical Ritter-type C-H Amination of Phenol.

The synthesis of paracetamol still relies on multistep protocols involving the utilization of a stoichiometric amount of oxidizing/reducing or other corrosive agents. Herein we report a regioselective electrochemical Ritter-type reaction at the C(sp2)-H of unprotected phenol toward the environmentally benign and direct synthesis of paracetamol. The reaction proceeds under exogenous oxidant- and catalyst-free conditions. The protocol is scalable, can be deployed to a variety of phenols, and offers a sustainable alternative for the synthesis of paracetamol.

Aza-Oxyallyl Cation Driven 3-Amido Oxetane Rearrangement to 2-Oxazolines: Access to Oxazoline Amide Ethers.

Herein, we report a highly facile and unprecedented activation of 3-amido oxetanes to synthesize 2-oxazoline amide ethers using a transient electrophilic aza-oxyallyl cation as an activating as well as an alkylating agent under mild reaction conditions. The aza-oxyallyl cation driven intramolecular rearrangement of 3-amido oxetanes to 2-oxazolines is the hallmark of this transformation and is a new addition to the reactivity profile of aza-oxyallyl cations.

Arylcyclopropane yet in its infancy: the challenges and recent advances in its functionalization.

Electronically unbiased arylcyclopropane functionalization has always been a challenge to organic chemists, and the emergence of donor-acceptor cyclopropanes (DACs) has not only vehemently overshadowed them but still dominates the cyclopropane chemistry. Unlike DACs, the absence of pre-installed functional groups makes it harder for them to activate and participate in a reaction. The field has witnessed considerably slow progress since its inception due to the inherent challenges. There are only a few strategies available to open arylcyclopropanes. Therefore, this work is still in its infancy stage in spite of these materials being one of the earliest known type of cyclopropanes. This review manifests the history, endeavors, and achievements alongside the associated challenges, opportunities, and the need for concerted efforts to accomplish the long-awaited golden age of arylcyclopropanes.

Electrochemical rearrangement protocols towards the construction of diverse molecular frameworks.

Rearrangement reactions constitute a critical facet of synthetic organic chemistry and demonstrate an attractive way to take advantage of existing structures to access various important molecular frameworks. Electroorganic chemistry has emerged as an environmentally benign approach to carry out organic transformations by directly employing an electric current and avoids the use of stoichiometric chemical oxidants. The last few years have witnessed a resurgence of electroorganic chemistry that has promoted a renaissance of interest in the development of novel redox electroorganic transformations. This review manifests the evolution of electrosynthesis in the area of rearrangement chemistry and covers the achievements in the field of migration, ring expansion, and rearrangements along with the mechanisms involved.

Electrochemical access to benzimidazolone and quinazolinone derivatives via in situ generation of isocyanates.

Isocyanates are the key intermediates for several organic transformations towards the synthesis of diverse pharmaceutical targets. Herein, we report the development of an oxidant-free protocol for electrochemical in situ generation of isocyanates. This strategy highlights expedient access to benzimidazolones and quinazolinones and eliminates the need for exogenous oxidants. Furthermore, detailed mechanistic studies provide strong support towards our hypothesis of in situ isocyanate generation.

Palladium-catalyzed regio- and stereoselective access to allyl ureas/carbamates: facile synthesis of imidazolidinones and oxazepinones.

Typically, transition metal catalysis enforces the stereodefined outcome of a reaction. Here we disclose the palladium-catalyzed regio- and stereoselective access to allylic ureas/carbamates and their further exploitation to diverse cyclic structures under operationally simple reaction conditions. This protocol features palladium-catalyzed decarboxylative amidation of highly modular VECs with good to excellent yield, minimal waste production, wide substrate scope, and low catalyst loading. In follow-up chemistry, we demonstrated the debenzylation of vinylic imidazolidinones to N-hydroxycyclic ureas and regioselective derivatization towards the facile synthesis of halohydrins and oxiranes under mild reaction conditions in good to excellent yields.

Lymphoepithelial Sialadenitis Involving HIV-Infected and Sjogren Syndrome Patients: A Cytologic Study.

Lymphoepithelial salivary gland cysts are rarely seen in autoimmune diseases particularly Sjogren syndrome as well as in HIV for which medical management is advocated. To study the morphology of these cysts, correlate with the disease process and assess the final outcome. Case series. Fine needle aspiration clinic. HIV-infected and autoimmune disease patients with lymphoepithelial cysts. Antiretroviral therapy for HIV-patients and anti-inflammatory drugs for Sjogren syndrome. Three HIV-infected patients (two children and one adult) and three middle aged female patients presented with parotid and submandibular cysts, two of which were bilateral along with submandibular (one each in the HIV and the autoimmune group). In the adult HIV-patient, the cyst was found at the inception of the disease while the other pediatric HIV-patients just crossed a decade. Of the other three cases of Sjogren syndrome, two were primary and one, secondary to rheumatoid arthritis. All the cysts regressed completely with treatment of the respective diseases which was confirmed by ultrasonograms. Lymphoepithelial cysts are produced by release of serous secretion by the acinar and ductal cells within the epithelial islands in the process of their destruction. Possibly, antibody mediated increased secretion in the initial stages also plays a role. Lymphoepithelial cysts of HIV patients may occur in the course of treatment, not necessarily in the beginning, though it resolves spontaneously. Lymphoepithelial cysts of primary or secondary Sjogren syndrome may be repressed sufficiently by anti-inflammatory/immunosuppressant treatment.

Mantle Cell Lymphoma of the Palatine Tonsil: A Rare Case Report.

INTRODUCTION: Primary mantle cell lymphoma (MCL) of the palatine tonsil without involvement of the regional lymph nodes is rarely reported. CASE REPORT: A 52-year-old male presented with complaints of a change in his voice over 3 months, with neither sore throat nor fever. Physical examination revealed right-sided grade IV and left-sided grade III tonsillar enlargement with prominent vessels. The patient underwent bilateral tonsillectomy. An initial histopathological report revealed chronic tonsillitis on the left side and suspicion of atypical lymphoproliferative disorder on the right. Immunohistochemically, the neoplastic cells were positive for Bcl2, CD20, CD5 and Cyclin D1 and negative for CD10, Bcl6 and CD3; thus a diagnosis of MCL was confirmed. CONCLUSION: MCL of the tonsil is rare. The microscopic diagnosis is challenging as the picture is very similar compared with other types of small cell lymphomas. A detailed immunohistochemistry panel is required for an accurate diagnosis.

The Role of Crush Cytology in the Diagnosis of Large-Intestine Lesions with Correlation on Histopathology.

OBJECTIVE: To study the efficacy of colonoscopic crush cytology as a convenient and near-accurate method to evaluate colonic neoplasms. STUDY DESIGN: Retrospective and cross-sectional. The original cytologic diagnoses were correlated with a histology report on 100 cases sent to the cytology laboratory over 2 years. RESULTS: Of the 100 cases, 25 were nonmalignant. Of the 75 malignant lesions, 72 could be identified as positive for malignancy on cytology. The false-positives consisted of 6 adenomas and 1 case of ulcerative colitis. Thus, sensitivity and specificity of cytology are 96 and 63.2%, respectively. Of the 6 adenomas diagnosed as malignant, 4 showed high-grade dysplasia, and the other 2 showed superficial ulceration with low-grade dysplasia on histopathology. The ulcerative colitis case showed widespread ulcers and regenerative/reparative features on biopsy. The 3 adenocarcinomas diagnosed s benign on cytology showed an occasional malignant cell with thickened nuclear borders and prominent central nucleoli. CONCLUSIONS: With careful attention to the cytomorphology, coupled with good clinical and endoscopic correlation, crush cytology of the large intestine is a reliable diagnostic tool. It categorizes lesions as malignant and benign with a high sensitivity, positive predictive value, and negative predictive value. Adenomas and reparative/regenerative changes seen in inflammatory bowel disease are major pitfalls in the cytology diagnosis of malignancy that may be averted by informing the endoscopic findings and clinical history. Cytology diagnosis saves time and gives proper feedback to the gastroenterologist.

Histomorphologic Spectrum in Hyaline Vascular Variant of Castleman Disease.

INTRODUCTION: Castleman Disease (CD) is a rare lymphopro-liferative disorder with heterogenous clinical and pathological features. It is a rare disease with mention in the rare disease data of the orphanet. It can present as unicentric or multicentric disease. Hyaline vascular variant and plasma cell variant are the two pathological subtypes. Hyaline vascular variant accounts for nearly 80% to 90% of unicentric cases. Hyaline vascular subtype variant has follicular and stroma rich subtype. AIM: To study the histomorphologic spectrum of hyaline vascular variant of CD. MATERIALS AND METHODS: Retrospective cross-sectional, observational study was undertaken from the archival data between January 2009 and April 2015. Only ten cases of hyaline vascular CD were identified after studying the histomorphological characteristics. Both follicular and interfollicular changes were studied in detail. RESULTS: The age of presentation ranged from 17 years to 59 years. Seven out of 10 cases were female. Site of presentation included cervical, inguinal, retroperitoneal, intra-abdominal and axillary. Six cases showed predominant follicular change. Two cases were sclerotic subtype. Two cases showed both follicular and interfollicular changes in equal proportion. Distribution of follicles throughout the lymphnode was seen in eight cases. Uniform sized follicles seen in seven out of ten cases. Small germinal centre with lymphocyte depletion was one of the uniform features seen in all 10 cases. Numerous high endothelial vessels were seen in nine cases. Twinning of germinal centre was seen in two cases. All ten cases showed concentric rings of small lymphocytes. Lollipop pattern was relatively rare feature seen in only two cases. CONCLUSION: Hyaline vascular variant of CD has considerable morphologic variation with few consistent features seen in most of the cases.

The role of discriminant functions in screening beta thalassemia trait and iron deficiency anemia among laboratory samples.

INTRODUCTION: Most important differential diagnosis for microcytosis and hypochromia is beta thalassemia trait (BTT) and iron deficiency anemia. AIM: To study the utility of discriminant functions (DFs) and red cell indices in distinguishing BTT and iron deficiency anemia. METHODS: The study is observational (cross sectional). A total of 350 patients, 43 BTT, and 307 iron-deficiency anemia reflecting actual disease prevalence were included. Their complete red blood cell parameters, hemoglobin A2, and serum ferritin level wherever required were obtained. Receiver operator characteristic curve was drawn for each DF and results compared with other studies. RESULTS: Among the six DFs, the highest sensitivity (97.7%) and specificity (98.6%) was shown, respectively, by Shine and Lal (S and L) and England and Fraser index (E and F) in identifying cases of BTT. Youden index of the Mentzer index (MI) was the highest (69.0) and S and L, the lowest (13.2) indicating MI to be the most efficient and the S and L, the least in differentiating the two entities. Red cell distribution width index (RDWI) showed the highest accuracy (91.6%), whereas S and L showed the least accuracy (29.6%). CONCLUSION: MI was the most efficient in discriminating BTT from iron deficiency anemia (IDA). RDWI stands to be the most accurate. S and L could at best be used as screening tool rather than DF. No study except one agreed with us because convenient sampling used in other studies generated bias in their results. Statistically, this study bears far more relevance than other studies because the sample distribution reflects the prevalence of IDA and BTT in the community.

The pitfalls in cytology diagnosis of poorly differentiated neuroendocrine carcinoma of lung and their treatment response.

CONTEXT: Lung is the most common site of small cell carcinoma (SCLC) - a poorly differentiated neuroendocrine carcinoma (PDNEC). SCLC comprises 15-20% of the invasive cancers of the lung. AIM: This study was conducted to appraise the accuracy and pitfalls of the diagnosis of PDNEC on cytology along with treatment responses if available. SETTINGS AND DESIGN: Retrospective study for 2 years yielded 21 cases on cytology. SUBJECTS AND METHODS: Slides of fine-needle aspiration of lymph nodes, the tumor, bronchial brush, and bronchoalveolar lavage specimens were used. The histological correlation was obtained as were treatment responses. RESULTS: Eighteen SCLCs were confirmed on review. Of these, 13 initial reports were concordant and five, discordant. The rest three cases which initially reported as SCLC were found to be negative (2) and combined SCLC (1). One SCLC with concordant initial and reviewed diagnoses failed to confirm on histopathology. The patients, all heavy smokers, were predominantly males in the seventh to eighth decade age group. The sensitivity and specificity of reviewed diagnoses were better than that of the original. The difference between histopathology and cytology diagnoses (reviewed and original) was statistically insignificant. All patients were categorized as "extensive stage" by positron emission tomography-computerized tomography, and five were treated with etoposide and cisplatin with/without radiotherapy. CONCLUSION: Age group (61-70) and gender (males) distribution were statistically significant. Intermediate variants of SCLC may be misdiagnosed as adenocarcinoma. Similarly, combined SCLC may be missed on cytology if the observer does not sustain a high index of suspicion. Unequivocal cytology diagnosis opposed to negative histopathology report demands repeat biopsy.

Evaluation of Fluorescent Staining for Diagnosis of Leprosy and its Impact on Grading of the Disease: Comparison with Conventional Staining.

INTRODUCTION: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae). Histopathological examination of skin lesion is the gold standard for diagnosis. We evaluated the possible role of fluorescent microscopy in this direction which is increasingly used for rapid screening. AIM: To compare the efficacy of auramine rhodamine stain with Ziehl-Neelsen and modified Fite-faraco staining in diagnosing M. leprae in tissue sections. STUDY DESIGN: Experimental, cross-sectional and retrospective study conducted for 4 years. METHODS AND MATERIALS: Skin biopsies of sixty clinically diagnosed leprosy patients were stained by Ziehl-Neelsen, Fite-Faraco and fluorescent stain. The presence of the bacilli and the bacillary index was scored for each case. The bacillary index by each staining methods were compared. STATISTICAL ANALYSIS: SPSS v 17 (IBM, New York) used for data analysis. Chi-Square test was used to calculate significance between differences. The p-value of <0.05 was considered as statistically significant. Pearson Correlation (r-value determined) was also used for comparison between groups. RESULTS: Sensitivity of fluorescent stain for indeterminate and borderline tuberculoid leprosies were 100% each. Positivity rates and mean bacteriological index with fluorescent stain was higher (43.3 and 11.5 respectively) as compared to that of Ziehl- Neelsen and Fite-faraco when the bacillary load was less (bacillary index < 3). There was significant correlation between the three staining types at higher bacillary load. There was a higher mean bacillary index with fluorescent stain as well as detection of an additional multibacillary case. CONCLUSION: Fluorescent method is more sensitive than modified fite-faraco method in detecting lepra bacilli in tissue sections especially in cases with bacillary index less than three. With its higher sensitivity, paucibacillary cases could be upgraded to multibacillary thus affecting treatement decisions.

Patterns of granulomatous responses in TB lymphadenitis and their correlation with treatment outcomes.

INTRODUCTION: Four patterns are noted in aspirates of TB lymphadenitis with or without concomitant HIV. They are granulomatous, necrotizing granulomatous, predominantly necrotizing and necrotizing suppurative designated pattern 1, 2, 3 and 4, respectively. The present study attempted to correlate granulomatous patterns, Acid Fast Bacilli (AFB) density with treatment outcomes. MATERIALS AND METHODS: The MGG and Papanicolaou stained slides of 56 lymphadenitis patients, 38 TB and 18 TB with seropositive HIV were studied for two years. The AFB were stratified into: 0 - nil (1 - ≤1 AFB, 2 - >1 but <10 AFB, 3 - ≥10 AFB)/10 fields. RESULTS: There were 35 males and 21 females. Eleven aspirates demonstrated AFB. TB+HIV lymphadenitis displayed a higher AFB score. TB+HIV lymphadenitis aspirates significantly showed higher grade granulomas and AFB. TB+HIV lymphadenitis required ≥8-month treatment. Granulomas (pattern 3 or 4) but not high AFB scores required longer treatment (>6 months). Treatment of AFB (≥1) often extended to >6 months. CONCLUSION: TB with seropositive HIV, possibly due to defective immune regulation exhibited granulomas (pattern 3 or 4) necessitating treatment for ≥8 months. Pattern 3 or 4 granulomas irrespective of HIV status demanded >6-month treatment.

Unusual lesions of the mediastinum.

OBJECTIVES: To study unusual lesions in the mediastinum, which do not originate from the thymus, lymph nodes, neural tissues or germ cells, and tissues that normally engender pathologic lesions in the mediastinum. MATERIALS AND METHODS: Of the 65 cases seen, 12 unusual lesion were encountered in a 5½ year period from 2006 to 2011. RESULTS: Two cases of nodular colloid goiter and one each of the mediastinal cyst, undifferentiated carcinoma, and Langerhans cell histiocytosis (LCH) affected the anterosuperior mediastinum. In the middle mediastinum, one case each of the mesothelioma, malignant gastrointestinal stromal tumor (GIST), squamous cell carcinoma (SCC), solitary fibrous tumor (SFT), and pleomorphic sarcoma (PS) was seen. One case of meningeal melanocytoma (Mme) and primary pleural liposarcoma (PL) involved the posterior mediastinum. Persistent disease was seen in LCH after 2 years. Of all the cases with malignant lesions, only the patient with SCC was alive after 1 year. CONCLUSION: The cases of primary and SCC, LCH, melanocytoma, liposarcoma and PS, and GIST are unexpected and very rarely have paradigms in the mediastinum. Radiologic impression and knowledge of the compartment where these lesions arose from hardly assisted in arriving at a definitive opinion as the lesions were not typical of this location. A high index of suspicion and the immunohistochemical profile facilitated the final diagnosis.