Use of discarded corneo-scleral rims to create cornea-like tissue.

BACKGROUND: Corneal disease is a major cause of blindness. Transplantation of cadaver-derived corneas (keratoplasty) is still the current therapy of choice; however, the global shortage of donor corneas continues to drive a search for alternatives. To this end, biosynthetic corneal substitutes have recently begun to gain importance. Here, we present a novel method for the generation of a cornea-like tissue (CLT), using corneo-scleral rims discarded after keratoplasty. METHODS AND RESULTS: Type I collagen was polymerized within the corneo-scleral rim, which functioned as a 'host' mould, directing the 'guest' collagen to polymerize into disc-shaped cornea-like material (CLM), displaying the shape, curvature, thickness, and transparency of normal cornea. This polymerization of collagen appears to derive from some morphogenetic influence exerted by the corneo-scleral rim. Once the CLM had formed naturally, we used collagen crosslinking to fortify it, and then introduced cells to generate a stratified epithelial layer to create cornea-like tissue (CLT) displaying characteristics of native cornea. Through the excision and reuse of rims, each rim turned out to be useful for the generation of multiple cornea-shaped CLTs. CONCLUSIONS: The approach effectively helps to shorten the gap between demand and supply of CLMs/CLTs for transplantation. We are exploring the surgical transplantation of this CLT into animal eyes, as keratoprostheses, as a precursor to future applications involving human eyes. It is possible to use either the CLM or CLT, for patients with varying corneal blinding diseases.

Effects of metformin on clinical, hormonal and relevant gene expression parameters in patients with acne: an observational study.

BACKGROUND: Acne vulgaris is associated with insulin resistance and elevated insulin-like growth factor-1 (IGF-1). Metformin is commonly used for treatment of acne in patients with polycystic ovarian syndrome (PCOS). However, the benefits of metformin in patients with acne in general are not well established. AIM: To study the effectiveness of metformin treatment in patients with acne but who do not have PCOS and to understand the mechanisms of action of metformin in acne not related to PCOS. METHOD: In this observational study, 30 patients with clinically confirmed acne vulgaris were treated with metformin (1000 mg daily) for 3 months without any other topical or systemic active intervention for their acne. The effect of metformin at the clinical, hormonal and genetic level was assessed. RESULTS: Metformin monotherapy significantly (P < 0.001) decreased the global acne grading score for acne followed by a marginal increase in insulin; with a significant (P = 0.03) increase in insulin-like growth factor-1 (IGF-1). A significant (P < 0.001) decrease in free androgen index resulting from a significant (P < 0.001) increase in sex hormone-binding globulin (SHBG) with decrease in testosterone was observed. Homeostasis model assessment insulin resistance (HOMA-IR) was not significantly changed. Forkhead box protein O1 (FOXO1) expression was significantly (P = 0.006) downregulated with metformin treatment at the mRNA level without any significant changes at protein level. Expression of lipogenic genes, namely HMGCR, SQLE and ACSL5 (P = 0.001, P = 0.03, P = 0.03, respectively) were also downregulated. CONCLUSION: Metformin monotherapy led to significant clinical improvement in acne, possibly by reducing testosterone, inhibiting FOXO1 and reducing lipid synthesis by decreasing the expression of lipogenic genes.

An artificial neural network for the prediction of the risk of malignancy in category III Bethesda thyroid lesions.

BACKGROUND: The diagnosis of cases of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) by fine needle aspiration cytology (FNAC) is challenging for both cytopathologists and clinicians. It is extremely difficult to predict the risk of malignancy based on cytological features alone. AIMS AND OBJECTIVES: In this study, we attempted to construct an artificial neural network (ANN) model to predict the risk of malignancy in FNAC cases of AUS/FLUS in thyroid lesions based on cytological features. MATERIALS AND METHODS: We included two groups of AUS/FLUS cases: (1) 29 cases of histopathologically proven malignancy, and (2) 32 cases that had either been histopathologically proven to be benign, or for which no progress of malignancy on follow-up had been observed in the last 2 years. Cytological characteristics were analysed semi-quantitatively by two independent observers (TS and PD). Based on these data, we tried to generate an artificial neural network (ANN) model to differentiate between malignant and benign cases. The performance of the ANN was assessed using the confusion matrix and receiving operator curve. RESULTS: There were 29 malignant cases of AUS/FLUS (histopathologically proven) and 32 benign/follow-up cases in this study. There were 41 cases in the training set, 9 cases in the validation set and 11 cases in the test set. In the test group, the ANN model successfully distinguished between all benign (5/5) and malignant cases (6/6). The area under the receiver operating curve was 1. CONCLUSION: The present ANN model is well structured and coherent to distinguish malignant from benign outcomes in AUS/FLUS cases on cytology smears with no error. This is an open-ended ANN model, and additional parameters and more cases could be included to make the model more robust.

Fine needle aspiration cytology of metastatic tumours to the thyroid.

BACKGROUND: Metastasis to the thyroid gland from non-thyroid sites is relatively rare and often poses a diagnostic difficulty on fine-needle aspiration cytology, as it often mimics primary thyroid neoplasms. METHODS: All cases of fine needle aspiration cytology (FNAC) of metastasis to the thyroid gland (2014-2022) were selected from the pathology database. The detailed cytopathological features and histopathology of the cases were studied. RESULTS: There was a total of 18 cases of secondary tumours of the thyroid. All cases had confirmed histopathological data. The most common primary tumours in our study were squamous cell carcinoma of the oesophagus (nine cases) followed by infiltrating ductal carcinoma of the breast (four cases), and one case each of renal cell carcinoma, neuroendocrine carcinoma of the lung, adenocarcinoma stomach and malignant melanoma and squamous cell carcinoma from vallecula. CONCLUSION: Metastasis to thyroid carcinoma is relatively uncommon. A history of malignancy, the presence of malignant cells amid benign thyroid follicular cells, unusual malignancy in a FNAC smear and immunocytochemistry are helpful in diagnosing such cases.

Fine needle aspiration cytology of a space-occupying lesion in the liver.

The fine needle aspiration cytology and histopathology of a space-occupying lesion in the liver.

Enzymatic vitreolysis using reengineered Vibrio mimicus-derived collagenase.

Purpose: Collagen is a key player contributing to vitreoelasticity and vitreoretinal adhesions. Molecular reorganization causes spontaneous weakening of these adhesions with age, resulting in the separation of the posterior hyaloid membrane (PHM) from the retina in what is called complete posterior vitreous detachment (PVD). Incomplete separation of the posterior hyaloid or tight adherence or both can lead to retinal detachment, vitreomacular traction syndrome, or epiretinal membrane formation, which requires surgical intervention. Pharmacological vitrectomy has the potential of avoiding surgical vitrectomy; it is also useful as an adjunct during retinal surgery to induce PVD. Previously studied enzymatic reagents, such as collagenase derived from Clostridium histolyticum, are nonspecific and potentially toxic. We studied a novel collagenase from Vibrio mimicus (VMC) which remains active (VMA), even after deletion of 51 C-terminal amino acids. To limit the activity of VMA to the vitreous cavity, a fusion construct (inhibitor of hyaluronic acid-VMA [iHA-VMA]) was made in which a 12-mer peptide (iHA, which binds to HA) was fused to the N-terminus of VMA. The construct was evaluated in the context of PVD. Methods: VMA and iHA-VMA were expressed in Escherichia coli, purified, and characterized with gelatin zymography, collagen degradation assay, fluorescamine-based assay, and cell-based assays. Two sets of experiments were performed in New Zealand albino rabbits. Group A (n = 10) received iHA-VMA, while group B (n = 5) received the equivalent dose of VMA. In both groups, saline was injected as a control in the contralateral eyes. Animals were monitored with indirect ophthalmoscopy, optical coherence tomography (OCT), and B-scan ultrasonography. Retinal toxicity was assessed with hematoxylin and eosin (H&E) staining of retinal tissue. Results: The activity of iHA-VMA and VMA was comparable and 65-fold lower than that of C. histolyticum collagenase Type IV. In the iHA-VMA group, all the rabbits (n = 10) developed PVD, with complete PVD seen in six animals. No statistically significant histomorphological changes were seen. In the VMA group, four of the five rabbits developed complete PVD; however, retinal morphological changes were seen in two animals. Conclusions: iHA-VMA displays targeted action confined to the vitreous and shows potential for safe pharmacologic vitreolysis.

Clericuzio-type poikiloderma with neutropenia in a patient from India.

A 9-year-old boy presented for evaluation of variegated skin pigmentation. Palms and soles revealed honeycombed hyperpigmented hyperkeratosis. Irregular, firm, skin coloured nodules suggestive of cutaneous calcification were present on both elbows. Total leucocyte count and absolute neutrophil count were 3720/mm3 and 420/mm3 respectively. The neutropenia was not cyclical. Systematic analysis of the whole exome data revealed a homozygous mutation in USB1 gene; chr16:g.58043892TA>-[1/1]. A final diagnosis of poikiloderma with neutropenia- Clericuzio type (PNC) was made. Naegeli Franceschetti Jadassohn, dermatopathia pigmentosa reticularis, PNC and dyskeratosis congenita, all can present with overlapping cutaneous manifestations. Subtle clinical details like thickened nails, hyperextensible joints, calcinosis cutis, characteristic facies and a preceding erythematopapular rash strongly favor the diagnosis of PNC. The index case highlights two novel findings: obliterated dermatoglyphics and mucin deposition (features not described hitherto in PNC).

Parathyroid Carcinoma: An Experience from the Indian Primary Hyperparathyroidism Registry.

OBJECTIVE: To describe the details of widely invasive parathyroid carcinoma (WIPC) patients admitted in the Endocrinology department of our institute during the last 22 years and to compare their clinical, biochemical, and hormonal profile with minimally invasive parathyroid carcinoma (MIPC) and sporadic parathyroid adenoma patients. METHODS: This is a retrospective analysis of data from the Indian primary hyperparathyroidism registry. RESULTS: Of the 547 primary hyperparathyroidism patients in the registry, 5 (2 men and 3 women) had WIPC (0.9%) and 7 (1 man and 6 women) had MIPC (1.3%), with median ages of 45 (interquartile range, 41-51) years and 47 (interquartile range, 28-48) years, respectively. Among the patients with WIPC, renal manifestations were present in 5 patients, skeletal manifestations in 4 patients, and palpable neck masses in 4 patients. Three patients had distant metastases and 2 had cervical lymph node involvement. All 5 patients had surgical resection of their cancers, with persistent disease in 4 patients, but all patients died within 2 years after surgery. One patient with MIPC had a palpable parathyroid nodule; none had lymph nodal or distant metastases. None of the patients with MIPC died during the median follow-up of 18 (interquartile range, 12-18) months. Patients with WIPC had significantly higher serum calcium level compared with sporadic parathyroid adenoma patients with skeletal and renal manifestations. CONCLUSION: Accurate histopathologic classification of parathyroid carcinoma is important as WIPC is associated with a more aggressive clinical course and a higher risk of mortality than MIPC.

Cystic Parathyroid Adenomas: An Enigmatic Entity and Role of Tc-99 m Sestamibi Scintigraphy.

OBJECTIVE: Functional cystic lesion of the parathyroid gland is a rare cause of primary hyperparathyroidism (PHPT). They have been postulated to arise from the hemorrhage and cystic degeneration in the parathyroid adenoma (PA). We intended to analyze their scintigraphic and histopathological findings since available literature is sparse. METHODS: Dual-phase 99 mTc-sestamibi planar and SPECT/CT scans performed from January 2014 to January 2020 in patients presenting with PHPT were retrospectively analyzed. The clinical, biochemical, and ultrasound features were collected. Planar and SPECT/CT imaging parameters were analyzed. Detailed histopathological analysis, along with post-surgical clinical and biochemical features of the patients who underwent surgery, was reviewed with a mean follow-up of 21.8 ± 20.1 months. RESULTS: Of the 979 scans analyzed, 10 showed cystic parathyroid lesions (M:F- 3:7, mean age 45.6 ± 15 years, range: 23-66). The predominant presenting features in patients were abdominal pain and renal stone disease, present in 60% of the patients. On planar scintigraphy, 90% of the patients had tracer avid distinct lesions, whereas tracer activity was seen in the solid part of the cystic lesions in all 10 patients on SPECT/CT, with cystic areas showing an attenuation of 23.1 ± 7.6 HU. Eight of these patients underwent surgery, with all showing PA with cystic changes on histopathology. Two of these patients also showed hemorrhage within the cystic spaces. CONCLUSION: Hemorrhage within a PA may give rise to cystic parathyroid lesions with PHPT. 99 mTc-sestamibi scintigraphy with dual-phase imaging and SPECT/CT may help in detecting this rare entity.

Etiology-, Sex-, and Tumor Size-Based Differences in Adrenocorticotropin-Dependent Cushing Syndrome.

OBJECTIVE: To examine demographic, clinical, and biochemical differences in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) based on etiology, sex, and tumor size. METHODS: This was a single-center study of 211 patients with ACTH-dependent CS followed for 35 years. Patients were stratified into 3 groups based on etiology: Cushing disease (CD)/transsphenoidal surgery, Cushing disease/total bilateral adrenalectomy (CD/TBA), and ectopic ACTH secretion (EAS). Patients were also stratified based on sex and tumor size (nonvisualized, microadenoma, and macroadenoma). RESULTS: CD was the commonest cause of ACTH-dependent CS (190; 90%). Most patients presented in the third decade (median age, 29 years). Clinical features, cortisol, and ACTH were significantly greater in the EAS group. The CD/TBA group had more nonvisualized tumors (22% vs 8%; P = .000) and smaller tumor size (4 vs 6 mm; P = .001) compared with the CD/transsphenoidal surgery group. There was female predominance in CD (2.06:1) and male predominance in EAS (2:1). Men had shorter duration of symptoms (2 years; P = .014), were younger (23 years; P = .001), had lower body mass index (25.1 kg/m2; P = .000), and had more severe disease (low bone mineral density, hypokalemia). Macroadenomas were frequent (46; 24.2%), and ACTH correlated with tumor size in CD (r = 0.226; P = .005). CONCLUSION: Our cohort presented at an earlier age than the Western population with a distinct, but slightly lower, female predilection. Patients with CD undergoing TBA had frequent negative imaging. Men had a clinical profile suggesting aggressive disease. Microadenoma and macroadenoma were difficult to distinguish on a clinicobiochemical basis.

Immunological response and clinical profile in patients with recurrent dermatophytosis.

BACKGROUND: An alarming increase in the number of patients with chronic and recurrent dermatophytosis has invoked the need to study the immunological parameters of the host. OBJECTIVES: To evaluate delayed type of hypersensitivity (DTH) response and immediate hypersensitivity (IH) response by flow cytometry evaluation of immune cells from peripheral blood and intradermal trichophyton skin test in patients with recurrent dermatophytosis. METHODS: A hundred patients with recurrent dermatophytosis and 50 controls (healthy controls and acute dermatophytosis controls) were included. Relevant risk factors for recurrence were analysed, and serum IgE levels were estimated. Flow cytometry evaluation of immune cells in peripheral blood and intradermal trichophyton skin test was done. Dermatophyte pathogens were isolated, and antifungal susceptibility was performed. RESULTS: Trichophyton mentagrophytes complex (95.84%) and T. rubrum (4.16%) were isolated in culture. Serum IgE was elevated in 83.15% cases (p = .01). IFN-γ+ cells (p = .0501, p = .0001, p = .0014), Th1 cells (p = .1197, p = .0024, p = .0169), IL-17+ cells (p = .0127, p = .0006, p = .0007) and Th17 cells (p = .0634, p = .0001, p = .0054) were reduced, and IL-4+ cells (p = .0108, p = .0175, p = .0018) were increased in cases. Intradermal test demonstrated negative DTH response in all cases (p < .001, p < .001, p < .001), strongly positive IH response in 6%, and borderline positive IH response in 85% cases (p = .018, p < .001, p < .001). Topical corticosteroids application, undergarment types (tight fit), poor frequency of washing clothes, family history of tinea, sharing of towels were significant risk factors for recurrent dermatophytosis. CONCLUSIONS: Reduced IFN-γ+ , Th1, IL-17+ and Th17 cells population along with impaired DTH response by the intradermal test was observed in patients with recurrent dermatophytosis.

Diagnostic Dilemma of Cutaneous Tuberculosis: Opening of the Pandora's Box.

ABSTRACT: Tuberculosis in all forms, that is, pulmonary (PTB) or extrapulmonary (EPTB), is a universal health problem. Cutaneous tuberculosis (CTb) remains one of the least studied and often under-reported variants of EPTB because of its wide and protean clinical presentation. The diagnosis of CTb remains challenging because of lack of sensitive and specific investigations for its diagnosis. The sensitivity of some of the traditional tests is low because of low concentration of mycobacteria in paucibacillary lesions. Besides it is difficult to distinguish between M. tuberculosis (MTb) and other mycobacterial species in skin biopsies morphologically. Molecular methods may target either MTb DNA or RNA, and serve as promising tools in the diagnosis of various forms of CTb, with high sensitivity and rapidity. This review is focused on diagnostic challenges of CTb and to discuss various methods and newer technologies for diagnosing CTb. This will help the dermatologists and dermatopathologists to elucidate and accurately diagnose CTb from other infectious granulomatous dermatitis for appropriate timely treatment of the patient.

Diagnostic Utility of Biplex/Multiplex Polymerase Chain Reaction in Infectious Granulomatous Dermatitis in North Indian Population.

BACKGROUND: A definite diagnosis of infectious granulomatous dermatitis (IGD) is difficult for both practicing dermatologists and dermatopathologists due to overlapping clinical and histomorphological features. We aimed to explore the role of multiplex polymerase chain reaction (PCR) for identifying a definite etiological agent for diagnosis and appropriate treatment in IGD in formalin-fixed paraffin-embedded tissue. MATERIALS AND METHODS: Sixty-two cases of IGD were included, excluding leprosy. The histochemical stains including Ziehl-Neelsen, periodic acid-Schiff, and Giemsa were performed in all cases. A multiplex PCR was designed for detection of tuberculosis (TB) (IS6110 and mpt64), fungal infections (ITS1, ITS2; ZM1, and ZM3), and leishmaniasis (kDNA). The results of histomorphology, histochemical stains, and multiplex PCR were compared. RESULTS: Among 62 cases, the sensitivity rate of PCR detection for organisms was 16.7%, 0%, 100%, 72%, 75%, and 66.7% in patients with TB, suggestive of TB, leishmaniasis, fungal infections, and granulomatous dermatitis not otherwise specified and granulomatous dermatitis suggestive of fungus, respectively. The TB PCR using IS6110 primers was negative in all cases; however, PCR using mpt64 primers was positive in 33.33% cases of scrofuloderma. The histochemical stains including Ziehl-Neelsen for acid-fast bacilli, periodic acid-Schiff for fungus, and Giemsa for Leishman-Donovan bodies showed positivity in 11.3%, 43.5%, and 3.2%, respectively. CONCLUSION: A multiplex PCR (Mycobacterium tuberculosis, Leishmania, and panfungal) is highly recommended in all cases of IGD where an etiological agent is difficult to establish by skin biopsy and histochemical stains along with a clinicopathological correlation. This will augment in appropriate treatment and will reduce empirical treatment and morbidity in such patients.

Clinical, morphological and immunohistochemical analysis of 13 cases of phosphaturic mesenchymal tumor - A holistic diagnostic approach.

BACKGROUND: Phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT) is a rare tumor characterized clinically by presence of tumor-induced osteomalacia (TIO), subsequent to elevated fibroblastic growth factor 23 (FGF23) levels. This study aims to analyse the morphological spectrum of PMT along with clinico-pathological correlation and immunophenotype profile of this rare tumor. MATERIALS AND METHODS: Detailed histological analysis of all tumors presenting with TIO over past 7 years was done retrospectively. Immunohistochemistry was performed in all cases for SATB2, STAT6, CD34, FGF23, ERG, S100 and smooth muscle actin (SMA). RESULTS: A total of 13 cases were analysed (8 female and 5 male) with mean age of 39.8 years. Five cases were arising from bone while 4 each from soft tissue and nasal cavity/paranasal sinus. All presented with hypophosphatemia, hyperphosphaturia, elevated serum FGF23 and features suggestive of osteomalacia. Histological examination revealed basophilic 'grungy' calcification seen in 7 (53.8%), osteoid formation in 8 (61.5%), chondroid matrix in 4 (30.8%), adipose tissue in 6 (46.2%), osteoclast-like giant cells in 9 (69.2%) and hemangiopericytomatous (HPC like) blood vessels in 7 cases (53.8%). HPC like vessels and adipose tissue were more common in nasal tumors while calcification was more common in tumors arising from bone. All cases showed immunoreactivity for SATB2 and clinical improvement following resection except one case with residual tumor. CONCLUSION: PMT shows varied histological pattern with various matrix components depending on the site of the tumor. Serum FGF-23 is a useful adjunctive marker for diagnosis.

Lacrimal Sac Actinomycosis: A Masquerade of Lacrimal Sac Malignancy.

A 60-year-old woman had blood-stained discharge with intermittent hemolacria from the left eye, of 3 months duration. The ophthalmic examination showed a firm, nontender, and immobile mass in the left lacrimal sac region. The sac regurgitation test was positive with purulent blood-stained discharge. Lacrimal punctum and canaliculi of both sides were normal. CT scan of orbits showed a hyperdense lesion in the left lacrimal sac region without bone erosion. A complete dacryocystectomy was performed, and the histopathology revealed actinomycosis of the lacrimal sac. At 14 months of follow-up visit, the patient has no clinical evidence of recurrence.

ACTH increment post total bilateral adrenalectomy for Cushing's disease: a consistent biosignature for predicting Nelson's syndrome.

PURPOSE: Nelson's syndrome (NS) is regarded as an aggressive complication of total bilateral adrenalectomy (TBA) for Cushing's disease (CD). This challenge may be addressed by using clinical criteria to guide frequency of neuroimaging to enable timely management of NS and also avoid unnecessary frequent imaging. METHODS: All patients (n = 43) with CD subjected to TBA over 35 years at a tertiary care centre were included. NS was defined as a newly appearing or expanding (> 2 mm) pituitary adenoma with or without ACTH levels exceeding 500 pg/ml. Pre-and post-TBA parameters like clinical symptomatology, cortisol, ACTH and radiology were analysed for the prediction of NS. RESULTS: NS developed in 39.5% (n = 17) patients with a median follow-up of 7 years. Half of them had new appearance, while rest had an expansion of pre-existing pituitary tumour. Majority (90%) had ACTH above 500 pg/ml. On Cox proportional hazards analysis, frequent discriminatory features of protein catabolism (≥ 4) (HR 1.15, CI 0.18, 7.06), proximal myopathy (HR 8.82, CI 1.12, 69.58) and annual ACTH increment of 113 pg/ml (HR 12.56, CI 1.88, 88.76) predicted NS. First post-operative year ACTH indices predicting NS included ACTH rise of 116 pg/ml and absolute ACTH of 142 pg/ml (sensitivity, specificity exceeding 90%). Annual ACTH increment exceeding 113 pg/ml, ≥ 4 discriminatory features and uncontrolled hypertension had the best overall prediction. CONCLUSION: Patients who developed NS had higher rebound rise of ACTH following TBA and a more severe disease phenotype at baseline. Consistent ACTH increment can be used as a marker for predicting the development of NS.

Artificial neural network model to distinguish pleomorphic adenoma from adenoid cystic carcinoma on fine needle aspiration cytology.

BACKGROUND: To differentiate pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) on fine needle aspiration cytology (FNAC) is often challenging to cytologists. AIMS: In the present study, we tried to make an artificial neural network (ANN) model from the FNAC smears to differentiate PA from ACC. METHODS: The detailed cytomorphological features were analysed on the FNAC of histopathology proven cases of PA (n = 35) and ACC (n = 33) and enumerated semi-quantitatively by two independent observers. These data were used to make an ANN model to distinguish PA from ACC on FNAC material. We used neuro-intelligence software to build the ANN model. The network architecture was 10-2-1. The heuristic search engine was applied to have this model. We used backpropagation neural network to teach ANN. At least 500 iterations were done to train the model. The efficacy of this ANN model was assessed with the help of the confusion matrix and receiver operating characteristic curve. RESULT: The data were separated automatically by the software as a training set (n = 48), validation set (n = 10) and test set (n = 10). The ANN model was able to differentiate every case (10/10) of PA and ACC in the final test set. The area under the receiver operating characteristic curve was 1. CONCLUSION: The currently built ANN model is competent to identify PA and ACC cases on FNAC. Additional parameters and new cases can be incorporated into this open-ended ANN model to make it more robust.

Fine-needle aspiration cytology of extra-salivary adenoid cystic carcinoma.

INTRODUCTION: Adenoid cystic carcinoma (ACC) is a ubiquitous tumour which can occur in several sites of the human body. Commonly, it affects the salivary glands but also can rarely occur in various extra-salivary locations. AIM: To study the clinical and cytological features of extra-salivary ACC on fine needle aspiration cytology. METHODS: In this paper, we included 27 patients with extra-salivary ACC on fine needle aspiration cytology over a period of 5.5 years. The complete cytomorphological spectrum of extra-salivary ACC was studied. RESULTS: The mean age of the patients was 50.2 years, with age ranging between 14 and 80 years. Male to female ratio was 1:1.7 with 17 females and 10 males. The most frequent primary site was the orbit, and the most frequent sites of metastasis were liver and lung. CONCLUSION: Cytopathologists should be alert about the full range of location as well as the cytological spectrum of extra-salivary ACC for greater precision in diagnosis and prompt treatment.

Fine needle aspiration cytology of primary and metastatic gastrointestinal stromal tumour.

AIM: To explore the cytological spectrum of the gastrointestinal stromal tumour (GIST) including its metastatic sites. MATERIAL AND METHODS: A total of 42 patients (45 sites) diagnosed with GIST or its metastases on fine needle aspiration cytology were studied over a period of 5 years. May-Grünwald Giemsa- and haematoxylin and eosin-stained smears were reviewed and analysed for the cytomorphological spectrum of GIST. RESULTS: Primary GIST alone was seen in 24 cases, E-GIST in eight cases and metastasis in 11 cases (one patient showing metastasis at two distinct sites), whereas concurrent primary and metastatic lesions were noted in two cases. Amongst primary sites, the most commonly affected location was stomach (n = 22), followed by ileum (n = 2), duodenum (n = 1) and rectum (n = 1). Extra-GIST was seen in retroperitoneum and pelvis (n = 3 each), omentum and mediastinum (n = 1 each). Fine needle aspiration cytology was done from 11 metastatic sites of GIST which included liver, gall bladder fossa, chest wall, and thigh. The classic spindle cell arrangement was the predominant cytological pattern. About 8.8% cases showed predominant epithelioid cell morphology and 15.5% cases had a mixed cytomorphology comprising of both spindle cell and epithelioid cell patterns. Nuclear pseudoinclusions, perinuclear vacuoles and multinucleation were seen in four cases. Immunocytochemistry on cell-block sections for confirmation was performed in 18 cases and all these cases showed strong c-KIT positivity. CONCLUSION: In this largest case series of cytomorphological diagnosis of GIST, we describe the cytomorphology and immunocytochemistry of primary and metastatic GIST. GISTs with predominant epithelioid cell morphology may pose a diagnostic dilemma therefore in all suspected cases of GIST, immunocytochemistry for c-KIT and/or DOG1 should be employed on cell-block preparations to confirm the diagnosis of GIST.

Minimally invasive parathyroid carcinoma-A missing entity between parathyroid adenoma and carcinoma: Scintigraphic and histological features.

PURPOSE: Minimally invasive parathyroid carcinoma (MIPC) is clinically and biochemically comparable with parathyroid adenoma (PA) though histopathologically differ from PA. MIPC is an intermediate of PA and parathyroid carcinoma (PC). In literature, there is no definite criterion to diagnose MIPC. Our aim was to evaluate and characterize the imaging and biochemical parameters with histological characteristics of MIPC. METHODOLOGY: Ten patients with MIPC were recruited from (single centre) Indian PHPT registry (www.indianphptregistry.com) from January 2014 to July 2018. Clinical, biochemical, imaging and histological features of MIPC patients were reviewed. RESULTS: The mean age of MIPC patients (n = 10; 3 males) was 39.9 ± 11.3 years (range: 17-50). All patients had an elevated preoperative parathyroid hormone (iPTH) level ranging from 427 to 2138 pg/mL (median: 1328). MIBI scan showed intensely avid and enlarged parathyroid tumours in all patients; LIPT in 6, RIPT in 3 and ectopic mediastinal in 1 with mean size of the tumours was 2.8 ± 1.1 cm. The mean of maximum standardized uptake value (SUVmax) of MIPC in F-18 fluorocholine PET/CT was 6.7 ± 1.1 (range 6.0-8.3). The mean tumour weight was 12 ± 9.5 g (range: 1.09-28). All MIPC patients had identified capsular invasion in 80% and vascular invasion in 50% only but there was no local invasion, lymph nodal or distant metastasis. The mean Ki-67 labelling index was 3.2 ± 2.7 (range 1.1-10). CONCLUSION: The study concluded that MIPC patients are less aggressive (on the basis of imaging and histopathological findings) and should be differentiated from parathyroid adenoma and carcinoma.