Osteochondroma versus Chondrosarcoma a Diagnostic Dilemma - a Case Report.

Introduction: Osteochondroma is a benign bone tumor, commonly seen as a bony outgrowth from the metaphysis of long bones, having a stalk and cartilage cap. They may be sessile or multiple and usually arise before 20 years of age with no growth beyond puberty. Malignant transformation is a rare complication seen in 1% of solitary cases and 3-5% in the hereditary multiple enchondromatosis variety. Here, we report a rare case of atypical benign osteochondroma with clinical and radiological features suggestive of a malignant transformation. Case Report: A 17-year-old boy presented to us with a complaint of swelling in his right thigh for 12 years. Radiological features were suggestive of malignant transformation, with bony outgrowth exhibiting heterogeneous calcification, local invasion, and a cartilage cap of size 2.5 cm. Bilateral lung nodules were detected on high-resolution computed tomography. Positron emission tomography scan showed no evidence of metastasis. The patient underwent a wide excision of the tumor and the histopathology revealed it to be a benign osteochondroma. It is an atypical presentation of osteochondroma in which we had a discrepancy in radio-histopathological correlation. Conclusion: In instances of diagnostic uncertainty concerning atypical osteochondroma, opting for an excisional biopsy serves as a prudent next step for the planning of subsequent management. The patient needs to be followed up regularly to look for recurrence or any other signs of metastasis.

Real-World Utilization of Radiation Therapy in Multiple Myeloma: An Analysis of the Connect MM Registry.

PURPOSE: Radiation therapy (RT) is an important treatment modality for patients with multiple myeloma (MM). Although patients are living longer with MM, they are more likely to have comorbidities related to treatment, such as bone pain; however, RT can provide symptom relief. To date, the characterization of patients who have received RT in the real-world setting has been limited. METHODS AND MATERIALS: The Connect® MM Registry is a large, US multicenter, prospective observational cohort study of adult patients with newly diagnosed MM from mostly community sites. RT utilization and outcomes were analyzed quarterly throughout treatment. Factors associated with RT use were identified via multivariable analysis. RESULTS: A total of 3011 patients were enrolled in the Connect MM Registry with 903 patients (30%) having received RT at any time. There was a significant difference (P < .05) in overall RT use among patients with an Eastern Cooperative Oncology Group performance status of 0 to 1 versus ≥2, International Staging System disease stage I/II versus III, a history of plasmacytoma or a novel agent in their first regimen, and any number of bone lesions or severe osteoporosis/fracture. RT use was associated with having bone lesions or severe osteoporosis (vs not having bone lesions). Additionally, RT use was associated with ethnicity (Hispanic vs not) and Connect MM Registry cohort (cohort 1 [enrolled 2009-2011] vs 2 [enrolled 2012-2016]). In the 6 months before death, increased RT use was associated with increasing number of treatment lines (P < .0001) and high- versus standard-risk disease (per International Myeloma Working Group criteria; P = .0028). CONCLUSIONS: Real-world results from the Connect MM Registry show RT is frequently used and is associated with clinical factors, including performance status and disease stage. Earlier in MM diagnosis, RT may be used as an adjunct to palliate symptoms or delay systemic therapy. Toward the end of life, RT is more frequently used for palliation when treatment options are often limited.

MASC Gets UNMASKED: Visiting a Rare Tumor with Emphasis on Cytomorphological Features.

Background: Secretory carcinoma (SC) is a newly described entity which has been often misdiagnosed earlier as acinic cell carcinoma on cytology. Diagnosing SC was initially based upon identifying the ETV6:NTRK3 fusion gene with the help of fluorescence in situ hybridization (FISH). Lately, with more knowledge of the reliable histomorphology, cytology, and immunohistochemistry features, definitive diagnosis can be confidently made without the help of FISH in almost every case. Materials and Methods: Six histologically confirmed cases of SC were studied. The cytology slides of all the six cases were retrieved and reviewed to identify the characteristic features which could have helped in raising the possibility of SC on fine needle aspiration cytology itself. Cell blocks were also studied, wherever available. Results: Patients were all male with average age of 35.2 years. The six cases in the current study demonstrated at least focal cytoplasmic vacuolization of varying sizes, papillae formations, and bland nuclear features on fine needle aspirate smears. It was also seen that S-100 and mammaglobin immunohistochemistry (IHC) are very helpful in confirming the diagnosis. Conclusions: The results of the current study highlight the cytomorphological features which may help in clinching the diagnosis SC on cytology itself. They also highlight certain cytological features which help to rule out the other differential diagnoses.

A Comprehensive Review on Chemistry and Biology of Tafamidis in Transthyretin Amyloidosis.

Transthyretin amyloid cardiomyopathy and Transthyretin amyloid peripheral neuropathy are progressive disease conditions caused by Transthyretin amyloidosis (ATTR) fibril infiltration in the tissue. Transthyretin (TTR) protein misfolding and amyloid fibril deposits are pathological biomarkers of ATTR-related disorders. There are various treatment strategies targeting different stages in pathophysiology. One such strategy is TTR tetramer stabilization. Recently, a new TTR tetramer stabilizer, tafamidis, has been introduced that reduces the protein misfolding and amyloidosis and, consequently, disease progression in ATTR cardiomyopathy and peripheral neuropathy. This review will provide a comprehensive overview of the literature on tafamidis discovery, development, synthetic methods, pharmacokinetics, analytical methods and clinical trials. Overall, 7 synthetic methods, 5 analytical methods and 23 clinical trials have been summarized from the literature.

Treatment Patterns, Survival, Quality of Life, and Healthcare Resource Use Among Patients With Triple-Class Refractory Multiple Myeloma in US Clinical Practice: Findings From the Connect MM Disease Registry.

BACKGROUND: Adults with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognosis, but the burden of TCR MM has not been well characterized. This study evaluated treatment patterns, overall survival (OS), health-related quality of life (HRQoL), and healthcare resource use (HCRU) among patients with TCR MM in US clinical practice. PATIENTS AND METHODS: Patients with TCR MM in the Connect MM Registry (NCT01081028; a large, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM) were included. Patient characteristics, treatment patterns, HRQoL, and HCRU were analyzed using descriptive statistics. OS was calculated using Kaplan-Meier methodology for the overall cohort and for patients with/without ≥1 post-TCR line of therapy (LOT). RESULTS: A total of 232 patients with TCR MM were included; 155 (67%) had ≥1 post-TCR LOT (post-TCR-Treated subgroup; median 9.9 months of follow-up). Most common post-TCR treatments were carfilzomib (47%), pomalidomide (40%), and daratumumab (26%); median treatment duration was 3.3 months. Median OS was 9.9 months in the overall population, 10.8 months in post-TCR-Treated patients, and 2.6 months for those with no new post-TCR LOT. HRQoL deteriorated and pain increased over 1 year of follow-up, with clinically meaningfully changes in EQ-5D (mean, -0.06 points) and FACT-G (mean, -9.9 points). 124 (53%) patients had ≥1 all-cause hospitalization and 58 (25%) had ≥1 MM-related hospitalization; median annualized length of stay was 35.3 and 42.9 days, respectively. CONCLUSION: The burden of TCR MM is substantial, emphasizing the need for more effective treatment options in the TCR setting.

Polyploidy on islands - concerted evolution and gene loss amid chromosomal stasis.

BACKGROUND AND AIMS: Polyploidy is an important process that often generates genomic diversity within lineages, but it can also cause changes that result in loss of genomic material. Island lineages, while often polyploid, typically show chromosomal stasis but have not been investigated in detail regarding smaller-scale gene loss. Our aim was to investigate post-polyploidization genome dynamics in a chromosomally stable lineage of Malvaceae endemic to New Zealand. METHODS: We determined chromosome numbers and used fluorescence in situ hybridization to localize 18S and 5S rDNA. Gene sequencing of 18S rDNA, the internal transcribed spacers (ITS) with intervening 5.8S rDNA, and a low-copy nuclear gene, GBSSI-1, was undertaken to determine if gene loss occurred in the New Zealand lineage following polyploidy. KEY RESULTS: The chromosome number for all species investigated was 2n = 42, with the first published report for the monotypic Australian genus Asterotrichion. The five species investigated all had two 5S rDNA signals localized interstitially on the long arm of one of the largest chromosome pairs. All species, except Plagianthus regius, had two 18S rDNA signals localized proximally on the short arm of one of the smallest chromosome pairs. Plagianthus regius had two additional 18S rDNA signals on a separate chromosome, giving a total of four. Sequencing of nuclear ribosomal 18S rDNA and the ITS cistron indicated loss of historical ribosomal repeats. Phylogenetic analysis of a low-copy nuclear gene, GBSSI-1, indicated that some lineages maintained three copies of the locus, while others have lost one or two copies. CONCLUSIONS: Although island endemic lineages show chromosomal stasis, with no additional changes in chromosome number, they may undergo smaller-scale processes of gene loss and concerted evolution ultimately leading to further genome restructuring and downsizing.

Highly cellular leiomyoma - A great histopathological masquerader of endometrial stromal sarcoma.

ABSTRACT: Leiomyoma is the most common benign uterine tumor, whereas endometrial stromal tumors are rare uterine tumors with limited clinical experience. The distinction between highly cellular leiomyoma and endometrial stromal sarcoma can pose a diagnostic challenge to the pathologists as both these tumors have considerable overlapping features on histology.

Is Atrophic Nonunion a Misnomer - A Hospital-based Prospective Cross-Sectional Study / Pseudoartrose atrófica é um termo incorreto? - Um estudo hospitalar transversal prospectivo

Abstract Objective The present study was conducted to estimate histologically the proportion of avascularity of fracture ends in case of nonunion of long bones. Methods A total of 15 cases of established quiescent nonunion were operated according to the standard protocol and the fracture ends were evaluated histologically. The biopsied tissue was briefly fixed with formalin, embedded with paraffin (FFPE), and 5-micron sections were stained with hematoxylin and eosin according to standard protocols. Immunohistochemistry with anti-CD31 antibody (JC70A clone, DBS) was performed manually using standard protocols. Results All cases of quiescent nonunion were included; radiologically, 2 cases were oligotrophic, and 13 cases were of atrophic nonunion. A total of 20% of the patients were females, 40% were in the age group between 31and 40 years old, and, radiologically, all cases were of atrophic nonunion. All cases showed positivity for CD-31 on immunohistochemistry. The blood vessel density was category I in 13.33% of the cases and category II in 86.67% of the cases. Four cases presented with mild inflammation and two presented with moderate inflammation. The average vessel count was 10 per high power field in the age groups between 20 and 30, 31 and 40, and 41and 50 years old. The age group between 61 and 70 years old showed an average vessel count of 4 per high power field. The difference in the vessel counts of oligotrophic and atrophic nonunion was not significant. No correlation was observed in the density of vessel count and duration of nonunion Conclusion The nomenclature for the classification of nonunion into atrophic, oligotrophic, and hypertrophic needs revision. Our findings do not support that atrophic and oligotrophic nonunion are histologically different.

Resumo Objetivo O presente estudo estimou a proporção de avascularidade histológica das extremidades das fraturas em caso de pseudoartrose de ossos longos. Métodos No total, 15 casos de pseudoartrose quiescente estabelecida foram operados de acordo com o protocolo padrão e as extremidades da fratura foram avaliadas histologicamente. Em resumo, o tecido biopsiado foi fixado em formalina e embebido em parafina (FFPE); secções de 5 mícrons foram coradas com hematoxilina e eosina de acordo com os protocolos padrões. A imunohistoquímica com anticorpo anti-CD31 (clone JC70A, DBS) foi realizada manualmente segundo protocolos padrões. Resultados Todos os casos de pseudoartrose quiescente foram incluídos; 2 eram de pseudoartrose oligotrófica e 13 eram de pseudoartrose atrófica à radiologia. Destes, 20% eram de pacientes do sexo feminino, 40% de indivíduos entre 31 e 40 anos de idade e todos os casos eram de pseudoartrose atrófica à radiologia. Todos os casos eram positivos para CD-31 à imunohistoquímica. A densidade dos vasos sanguíneos era de categoria I em 13,33% dos casos e de categoria II em 86,67%. Quatro casos apresentavam inflamação branda e dois apresentavam inflamação moderada. O número médio de vasos era de 10 por campo de alta potência na faixa etária de 20 a 30, de 31 a 40 e de 41 a 50 anos. A faixa etária de 61 a 70 anos apresentava, em média, 4 vasos por campo de alta potência. A diferença nos números de vasos em pseudoarthroses oligotróficas e atróficas não foi significativa. Não houve correlação entre a densidade de vasos e a duração da pseudoartrose. Conclusão A nomenclatura de classificação da pseudoartrose em atrófica, oligotrófica e hipertrófica precisa ser revista. Nossos achados não indicam que a pseudoartrose atrófica e oligotrófica sejam histologicamente diferentes.

Tracing, Tracking and Treating COVID-19 Associated Rhino-Orbito Cerebral Mucormycosis (ROCM).

Surge in the number of mucormycosis cases following second wave of coronavirus disease-19 (COVID-19) infection posed several diagnostic and prognostic challenges. This study was aimed to describe clinical, diagnostic features and survival outcomes among patients of mucormycosis in post COVID-19 context. Retrospective chart review. This study included 44 COVID-19 positive screened cases who presented with clinical features suggestive of mucormycosis. Demography, clinical profile, diagnostic findings, and the treatment outcome are studied. Medical and surgical outcomes are summarised as frequencies and percentages. The reliability of microbiological, and radiological findings against the pathological findings was analyzed using Kappa statistics (k). Based on constellation of microbiological, pathological and radiological findings 28 cases (63%) confirmed with mucormycosis infection. The mean (SD) age was 54.9 (12.9) years and two-third were males. The majority (90%) of cases presented with the feature of facial swelling, headache nasal blockade. Inpatient care for treatment of COVID-19 was recorded in 33 (75%). Diabetes mellitus was the commonest comorbidity in 27 (61.4%), 38 (86.4%) cases were treated by steroids and 30 (68.2%) were given oxygen therapy. There is a strong agreement (k = 0.83) between pathological and microbiological investigations. In thirty-eight cases (86.3%) remission was achieved when assessed after 8 weeks. Of the 44 cases, four patients died. The results of the current study suggest that the disease residues and/or recurrences in critical areas are frequent in mucormycosis. However, using the strategy of screening at risk patients, diagnosing, treating them with combination of antifungals, surgical debridement, and timely follow up may help in improving outcomes as compared to pre COVID-19 era.

Acute non-puerperal uterine inversion ascribed to malignant mixed Mullerian tumor of uterus: a rare presentation.

Non-puerperal uterine inversion is an extremely uncommon condition, and its occurrence due to malignant mixed Mullerian tumor (MMMT) of the uterus is quite exceptional. We report one such case of acute non-puerperal uterine inversion ascribed to MMMT in a 77-year-old postmenopausal woman. Such a case poses a diagnostic and management dilemma, and prior knowledge may result in a successful outcome.

Primary pleural liposarcoma: a rare differential for an opaque hemithorax.

Primary pleural liposarcoma (PPL) is a rare primary malignant pleural tumour originating from primitive mesenchymal tissue. We report the case of a 25-year-old man with a 6-week history of shortness of breath, cough, chest pain and hoarseness of voice. Chest X-ray showed a left opacified hemithorax, and thoracic CT scan revealed a large, heterogeneous, hypodense mass in the left hemithorax. The patient was taken up for ultrasound-guided core biopsy of the mass lesion, and histopathological examination revealed the diagnosis as a pleomorphic variant of PPL. We highlight the importance of considering PPL as a differential diagnosis in cases of large hemithoracic masses.

Evaluation of Histomorphological Parameters to Predict Occult Nodal Metastasis in Early-Stage Oral Squamous Cell Carcinoma.

OBJECTIVE: The oral squamous cell carcinoma (OSCC) treatment protocol depends upon lymph node metastasis. Elective neck dissection for early-stage OSCC (pT1/T2) elective neck dissection reduces the morbidity rate. It also reduces the overall survival and thus it becomes important to detect lymph node metastasis in early-stage OSCC. MATERIAL AND METHOD: Various histomorphological parameters have been studied to predict nodal metastasis in early-stage OSCC. We aim to evaluate these parameters in the context of nodal metastasis. 78 cases of early-stage OSCC were included in the study with histopathologic parameters like tumor size, grade, tumor depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion (PNI), worst pattern of invasion (WPOI), and lymph node level. RESULTS: Out of the 78 patients, 32 patients had lymph node metastasis. T stage, DOI, LVI, and WPOI showed statistically significant deviance from the null model (P-values of 0.007, 0.01, 0.04 and 0.02 respectively). The Odds Ratio (OR) of T stage, DOI, LVI and WPOI were 4.45 (95% C.I =1.47-14.1), 4.4 (95% C.I =1.32-15.88), 8.12 (95% C.I =1.002-198.20), and 3.39 (95% C.I =1.24-9.74) respectively. On multivariate analysis (Firth logistic regression) using DOI, LVI, and WPOI as independent variables, only T-stage and WPOI retained statistical significance. CONCLUSION: The prognostic information supplied by evaluating DOI, LVI, and WPOI warrants the inclusion of these parameters in the standard reporting format for all cases of OSCC.

Primary Malignant Melanoma of the Oral Cavity: A Retrospective Study From a Tertiary Care Centre of North India.

BACKGROUND: Mucosal melanoma is a rare but aggressive tumor associated with a poor prognosis arising from pigmented cells called melanocytes. They are usually asymptomatic and present in an advanced stage. It has an aggressive clinical outcome and is proven to be of poor prognosis. MATERIALS AND METHODS: This is a retrospective review of the computer database and clinical records at the All India Institute of Medical Sciences, Rishikesh, India. The data between 2018-2022 were reviewed for all small biopsy or excision specimen-proven cases of oral mucosal melanoma. RESULTS: The most common site of involvement in the head and neck region is the nasal cavity and paranasal sinuses. In this retrospective study from our institute, all three cases presented involved oral cavities. The median age of presentation was 51 years. Some literature specifies male preponderance. Our patients presented clinically with a black nodule in the oral cavity, which was increasing in size and associated with bleeding. A biopsy performed confirmed the diagnosis of melanoma based on the morphology and immunohistochemical profile of the tumor cells. CONCLUSION: Surgical resection is the mainstay treatment, followed by radiation postoperatively to reduce local and regional recurrence. Mucosal melanoma has a poor prognosis, and the majority of patients develop incurable metastatic disease.

Comparison of Fluorometric and UV Spectrophotometric Findings for DNA Isolated From Formalin-Fixed Paraffin-Embedded Blocks, Fine Needle Aspiration Cytology Smears, and Blood.

INTRODUCTION: Fine needle aspiration cytology (FNAC) smear may serve as a convenient sample for DNA extraction for molecular pathology in addition to more commonly used formalin-fixed paraffin-embedded (FFPE) sections. DNA quantification done by fluorometer is more accurate than UV vis spectrophotometer regardless of the source. This study was conducted to compare DNA yield and quality from cytology smears, FFPE sections and peripheral blood using both fluorometer and spectrophotometer. Further, introspection was made to check for the adequacy of DNA extracted from cytology smears with respect to DNA extracted from core biopsies. METHOD: DNA was extracted from 10 fresh peripheral blood samples, core biopsies and FNAC smears. The DNA was quantified using a fluorimeter and UV vis spectrophotometer in all cases. RESULTS: Statistically significant difference was seen between the data obtained from UV vis spectrophotometry and flourometry. The quantity of DNA extracted from FNAC smears was higher than that of core biopsy as per fluorometry data (mean DNA of core biopsy = 1.9ng/µl, of FNAC = 3.3ng/µl). CONCLUSION: DNA estimation by fluorometry is more accurate and precise than spectrophotometry in FFPE, FNAC and whole blood samples. DNA yield from FNAC slides is comparable to that from core biopsies.

Epistaxis: the cause found beyond the nose.

Renal cell carcinoma (RCC) is a malignant disease that is often diagnosed at a metastatic stage. The head and neck represent up to 3% of the metastatic RCC, and the paranasal sinus area is one of the least involved sites. Here, we introduce the case of a 74-year-old female patient who presented with a history of traumatic nasal bleed. A cranial computed tomography scan and magnetic resonance imaging showed a fronto-ethmoidal mass with pachymeningeal involvement. A nasal biopsy from the paranasal sinuses was taken. On histopathological examination, metastatic clear cell carcinoma was the main hypothesis, which later was confirmed to be RCC on immunohistochemistry. On further radiological examination, an exophytic mass was depicted in the kidney's upper and middle pole. The patient had no renal complaints and was asymptomatic. Fronto-ethmoidal sinus is a rare site for metastatic RCC, especially in cases where the patient is asymptomatic. Early detection by keeping RCC metastasis as the differential diagnosis in such cases can lead to early treatment and improve the overall survival of the patient.

Migraine-like headaches associated with nickel allergy requiring removal of atrial septal defect closure device.

There is a deficit of literature regarding the association between nickel allergy-induced symptoms and implanted devices. This report describes a case of nickel allergy causing debilitating migraine-like symptoms, failing to resolve with medical therapy, requiring surgical removal of the device and repair of the defect.

Accuracy of Breast Fine-Needle Aspiration Biopsy Using the International Academy of Cytology Yokohama System in Clinico-Radiologically Indeterminate Lesions: Initial Findings Demonstrating Value in Lesions of Low Suspicion of Malignancy.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) in breast lesions offers accurate results in differentiating benign and malignant lesions. However, its role is unclear when core-needle biopsy (CNB) is available, the latter providing additional information regarding tumor grade, invasion, and hormone receptor status in malignant lesions. In benign breast lesions, especially in BIRADS category 4a and 4b, FNAB, and CNB provide similar pathological information, whereby FNAB may serve as a more rapid and cost-effective investigation. The study was planned to reevaluate the diagnostic accuracy of FNAB in BIRADS category 4a, 4b, and 4c lesions. MATERIALS AND METHODS: FNAB and biopsy reports of all patients with breast lesions sent between September 1, 2018, and November 30, 2020, were collected and the International Academy of Cytology (IAC) Yokohama category and BIRADS score were recorded for each case. The rate of malignancy and the accuracy of FNAB in diagnosing malignancy were calculated for each BIRADS 4a, 4b, and 4c subgroup. RESULTS: A total of 249 cases of BIRADS 4 lesions had corresponding cytology and histopathology diagnoses. FNAB showed high diagnostic accuracy in all BIRADS groups. A benign categorization was associated with a very low number of false-negative diagnoses, especially in BIRADS 4a lesions. CONCLUSION: The study reconfirms the excellent accuracy of breast FNAB using the IAC Yokohama system in diagnosing breast malignancies. Furthermore, BIRADS 4a lesions found to be belonging to the cytological benign category may be excluded from CRB and kept on clinical follow-up.

Prospective evaluation of accuracy of fine-needle aspiration biopsy for breast lesions using the International Academy of Cytology Yokohama System for reporting breast cytopathology.

BACKGROUND: Classification of breast lesions into different cytological groups can accurately be done using the International Academy of Cytology (IAC) Yokohama System for reporting breast cytopathology. Fine needle aspiration biopsy (FNAB) of breast lesions has been considered to be the primary investigation in detecting breast cancers, especially in low-cost settings. The main objective of this study was to prospectively re-confirm the diagnostic accuracy of breast FNAB using the IAC Yokohama system. Additionally, separate secondary subgroup analysis was done to confirm the accuracy of breast FNAB excluding lymph-node positive and lymphadenopathy positive tumors. MATERIAL AND METHODS: A prospective study was done on patients undergoing biopsy of breast lesions between September 01, 2019 and November 30, 2020 (519 biopsies on 487 unique patients). Of these 519 histopathology biopsies, 505 had corresponding FNAB report of the same site. The FNAB was reported using the IAC Yokohama system and the most suitable category was allotted in every case. The rates of malignancy for each category and the accuracy of breast FNAB in diagnosing malignancy were calculated. RESULTS: Of the total 487 patients, 120 cases were benign on histology, while 367 were malignant. The rates of malignancy in benign, atypical, suspicious and malignant categories were 5%, 25%, 71%, and 99.7%, respectively. The diagnostic accuracy of atypical, suspicious and malignant categories was calculated as 90.1%, 95.2%, and 93.3%, respectively. CONCLUSION: The high diagnostic accuracy for each BIRADS category suggest excellent accuracy for Breast FNAB using the IAC Yokohama system.