Evaluation of the follicular patterned thyroid lesions based on the WHO 2022 criteria with an emphasis on the grey-zone lesions.

Follicular-patterned thyroid nodules (FPTN) are classified byWHO-2022 into benign, borderline and malignant categories. There are however, grey-zone lesions that pose a diagnostic challenge due to ambiguity in defining criteria and inter-observer variability. WHO-2022 has enumerated specific diagnostic criteria for these lesions. Accurate categorization of morphologically similar TNs is vital to reduce overtreatment of indolent lesions. In this study, we have reclassified FPTNs according to WHO-2022 criteria, emphasizing on grey-zone lesions. We studied the utility of immunohistochemistry (IHC)-CD56, HBME-1 and CK19 in distinguishing benign from malignant nodules and BRAFV600E IHC to better distinguish the (widely-invasive) encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) from infiltrative FVPTC. Only those cases with dominant nodule having follicular pattern histology were included and re-evaluated for following histopathological features-focality, encapsulation, circumscription, nuclear PTC features, capsular-invasion, angio-invasion, papillae and necrosis. IHC findings for above-mentioned markers were noted. Seventy-nine cases met the inclusion criteria. Amendment of original diagnosis was done in 19 % cases. BRAFV600E IHC was positive in the two cases of infiltrative FVPTC while it was negative in all nine IE (invasive encapsulated) FVPTCs. Diffuse HBME1 was noted in most malignant nodules (61 %) while CD56 was expressed more often in benign lesions (70 %). CK19 was positive in lesions displaying nuclear PTC features (86 %). Using WHO 2022 criteria, we were able to re-classify follicular thyroid lesions with greater confidence. Appropriate IHC panel in adjunct to histology aids in categorizing challenging cases.

Alveolar soft part sarcoma: A case report and review of the literature.

Alveolar soft part sarcoma (ASPS) is a rarely diagnosed tumour of deep soft tissue origin. This tumour is more common in adolescents and young adults and has a slowly progressive clinical course, which often leads to delayed diagnosis and treatment. It is highly vascular, can be confused with other entities like haemangiomas and arteriovenous malformations clinically and radiologically and is thus challenging to report on fine needle aspiration cytology (FNAC). Diagnosing the tumour is difficult on cytology, so knowledge of this entity and the differentials with its morphological mimics on cytology is required for timely diagnosis and early management of the patient. We report a case of ASPS in a young female who presented with a large, painless swelling in the thigh, diagnosed on cytology combined with ancillary testing with immunohistochemical markers.

Differentiating Biliary Atresia From Idiopathic Neonatal Hepatitis: A Novel Keratin 7 Based Mathematical Approach on Liver Biopsies.

BACKGROUND AND AIMS: Differentiating biliary atresia (BA) from idiopathic neonatal hepatitis (INH) is vital in routine pediatric practice. However, on liver biopsy, few cases offer a diagnostic challenge to discriminate these entities with certainty. Bile ductular reaction (DR), intermediate hepatobiliary cells (IHBC) and extra-portal ductules (EPD) indicate progenitor cell activation, as a response to various hepatic insults. The present study aims to quantify DR, IHBC and EPD by Keratin 7 (CK7) immunohistochemistry (IHC) in BA and INH and to devise a mathematical approach to better differentiate the two, especially in histologically equivocal cases. METHODS: A total of 98 cases were categorized on biopsy as BA, INH or equivocal histology, favoring BA or INH. CK7 DR mean, IHBC mean and EPD mean values were compared between BA and INH. A formula was derived to help distinguish these two entities, the cut-off value, sensitivity and specificity of which were determined by receiver operating characteristic (ROC) curve. This formula was applied and validated on histologically equivocal cases. RESULTS: Univariate logistic regression revealed significant difference between BA and INH with respect to CK7 DR and CK7 EPD mean (p < 0.001 in both); however, CK7 IHBC mean was not significant (p = 0.08). On multivariate logistic regression, only CK7 DR had significant impact on diagnosis (p < 0.001). A formula: (CK7 DR)2 + (CK7 EPD)/(CK7 IHBC) was derived to help distinguish BA from INH. Cut off value of 10.5 and above, determined by ROC curve, favored a diagnosis of BA (sensitivity= 93.4%, specificity= 94.6%). Histologically equivocal and discrepant cases could be correctly categorized using this formula. CONCLUSIONS: Formula using CK7 IHC parameters may aid pathologists better distinguish BA from INH, especially in histologically equivocal cases.

Characterization of Toll-like receptor transcriptome in squamous cell carcinoma of cervix: A case-control study.

OBJECTIVE: Human papillomavirus (HPV) is a proven etiological agent for cervical cancer However, not all HPV infections result in cervical cancer. The mechanisms of host immune system to prevent/control HPV infection remain poorly understood. Toll-like receptors (TLRs) are a system of innate immune defense. HPV has been demonstrated to modulate TLR expression and interfere in TLR signaling pathways, leading to persistent viral infection and carcinogenesis. The aim was to study the relative gene expression of TLRs in cervical squamous cell carcinoma (SCC). METHODS: Gene expression profile of TLRs 1 to 9 was examined in 30 cervical SCCs and an equal number of normal cervical tissue samples using a PCR array platform. Gene expression studies for TLRs 3 and 7 were validated by western blotting. RESULTS: HPV was detected in all cases and in none of the controls (p<0.0001). HPV16 was the preponderant (83.3%) subtype. A significant downregulation in the relative gene expression of TLR3 (p<0.0001), TLR4 (p<0.0005) and TLR5 (p<0.0001) was observed in cases. A significant upregulation for TLR1 was observed (p=0.006). Although TLRs 2, 7, 8 and 9 were upregulated and TLR6 was downregulated, it was not significant. The western blot performed with antibodies against TLRs 3 and 7 confirmed the findings of the gene expression studies. CONCLUSIONS: A significant downregulation in the gene expression of TLRs 3, 4 and 5 and upregulation of TLR1 was observed in cervical SCC as compared to controls. Study results evoke the proposition for investigating TLRs 3, 4 and 5 agonists for therapeutic exploration.

Plasma cell myeloma with double M bands on Serum protein electrophoresis: A diagnostic conundrum?

ABSTRACT: Plasma cell myeloma (PCM) is a monoclonal gammopathy (MGM) characterized by proliferation of abnormal clone of plasma cells infiltrating the bone marrow with consequent end organ damage. The clonal plasma cells secrete a single clone of immunoglobulins (Ig) leading to presence of M-protein in the serum and/or urine. The M-protein is appreciated as a discrete band on serum protein electrophoresis (SPE) in the gamma globulin region, also called the M-band. Biclonal gammopathy (BGM) occurs due to neoplastic transformation of a plasma cell clone undergoing Ig class switching or due to an independent neoplastic transformation event yielding proliferation of unrelated plasma cell clones, therefore resulting in two distinct M-bands on SPE. It is, however, vital to distinguish a true BGM from an apparent one (MGM presenting with two distinct bands on SPE) so as to make an accurate diagnosis. Hereby, we report a case of a 61-year-old man, diagnosed with PCM and presenting with two discrete bands on SPE (simulating a BGM) which turned out to be monoclonal in nature.

Primary leiomyosarcoma with osteosarcomatous differentiation of the breast.

Primary leiomyosarcoma with osteosarcomatous differentiation of the breast is an uncommon entity. We present the case of a 37-year-old female who presented with a lump in the breast and pulmonary lesions on PET-CT, for which she underwent a toilet mastectomy. Histopathological examination revealed a tumor with cells arranged in sheets. These tumor cells had moderate eosinophilic cytoplasm, highly pleomorphic, irregular hyperchromatic nuclei, coarse chromatin, and prominent nucleoli. Areas with spindle-cell morphology were noted. Osteoid was seen intermingling with the tumor along with numerous osteoclast-like multinucleate giant cells. A wide panel of Immunohistochemistry was applied, and Desmin, h-Caldesmon, SMA, and Vimentin were positive. The patient died 3 months post-surgery and had a recurrence at the surgical site.

Gastric outlet obstruction as an unusual presentation of metastatic breast carcinoma.

Gastrointestinal (GI) metastasis from breast carcinoma is a rare occurrence. If metastasis occurs to the stomach/duodenum, it can present with symptoms of gastric outlet obstruction (GOO). Hence, it clinically mimics a variety of benign as well as malignant causes of GOO, including primary malignancy. GI metastasis from breast carcinoma occurs several years after the primary diagnosis and sometimes may be the first presenting symptom. If clinical records are not available, it may be misdiagnosed as poorly differentiated adenocarcinoma on biopsy. A high index of suspicion, subtle histologic clues, and appropriate immunohistochemistry helps in clinching the right diagnosis. Hereby, we report the case of a 55-year-old female who presented with metastasis to the duodenum 8 years post mastectomy which mimicked a primary ampullary/periampullary tumor.

Invasive cystic hypersecretory carcinoma of the breast.

Cystic hypersecretory carcinoma (CHC) of the breast is a rare variant of ductal carcinoma, characterized by variably sized cysts lined by micropapillary fronds to proliferative pseudostratified columnar epithelium. It includes a spectrum of morphological features ranging from clearly benign cystic hypersecretory hyperplasia (CHH), CHH with atypia to invasive CHC. Only 20 cases of invasive CHC have been reported to date. We report a case of a 49-year-old female who presented with a palpable breast lump and nipple discharge. Gross examination showed variable-sized cysts lined by solid grey white tumors. On microscopic examination, cysts were lined by micropapillary fronds with eosinophilic colloid-like secretion with a focus of invasion. A diagnosis of invasive CHC was made. Since there are limited case reports, our understanding of its biological behavior, prognostic factors, and genetic basis is limited.

Intussusception in a child with Acute Lymphoblastic Leukemia: a remarkable presentation with literature review - a case report.

BACKGROUND: Gastrointestinal complications are not uncommon in patients of Acute Leukemia. Intussusception as a complication in leukemia, although described, is exceedingly rare. Also, it is usually seen after chemotherapy and not as a part of the native disease process. This case report aims to highlight such a rare association which warrants clinical and pathological attention. CASE PRESENTATION: A 14 year old male presented with an acute abdomen. Initial routine investigations revealed a deranged blood picture. On further examination of bone marrow aspirate, biopsy and detailed immunohistochemical studies a diagnosis of B-Acute Lymphoblastic Leukemia (B-ALL) was made. Concurrent ultrasound of the abdomen to find a cause for severe abdominal pain revealed an Ileo-colic intussusception. The patient was started on steroids; however he succumbed to his illness after two days, before surgery could be attempted. CONCLUSION: Rare presentations of relatively common diseases are a hurdle for timely and effective medical intervention. Although a rare condition in itself in leukemic patients, the occurrence of Intussusception in this particular patient, especially when no chemotherapy was initiated, is a very rare event. This case report was made to add to the relatively scarce literature available on this particular association. As it is a surgically treatable condition and since delay in diagnosis may lead to poorer prognosis, possibility of co-existence of ALL and intussusception should be borne in mind by all treating physicians and hematopathologists for effective patient care.

Atypical Presentation of Pseudoxanthoma Elasticum in Two Siblings from North India.

Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder occurring due to metabolic defect in the liver and manifesting predominantly in the skin, eyes and arteries. It shows characteristic yellowish papules on the skin around the nape of neck along with looseness of skin over flexural surfaces. PXE shows marked phenotypic heterogeneity. Complications related to arterial wall and retinal Bruchs' membrane calcification occur later in life; early diagnosis therefore helps keep patient on follow up for development of the same. In Indian patients, classic skin changes may be missed clinically making histopathology pivotal in diagnosis and patient management.

Solitary adult xanthogranuloma in external auditory canal: Cyto-histopathological correlation of an uncommon entity at an uncommon site.

Juvenile xanthogranulomas (JXG) are the most common type of self-limiting non-Langerhans cell histiocytosis (LCH) usually presenting in infancy and early childhood. Clinically, they present as solitary to multiple rounded cutaneous nodules which resolve over time. Adult type xanthogranulomas (AXG), though histologically similar to JXG, are usually single and do not regress spontaneously. AXG arising in the external auditory canal (EAC) is a rare occurrence with very few cases reported in literature. We present a case of AXG in a 48-year-old man, arising from the right EAC. This case is unique as it is the only case to be described with both cytology and histology correlation. On cytology, smears showed scattered foamy histiocytes, inflammatory cells and thick stromal fragments. Cytology differential diagnoses of xanthomatous lesion, benign fibrous histiocytoma (BFH) and ceruminous adenoma were given; final diagnosis was deferred to histopathology which confirmed it to be an AXG. Thus, it is important to keep the diagnosis of AXG in mind while dealing with solitary polypoidal lesions in EAC showing prominent foam cell component. Lipidised BFH forms a close differential diagnosis, however can be excluded by subtle points on cytology and on histopathology.

Primary leiomyosarcoma with osteosarcomatous differentiation of the breast

ABSTRACT Primary leiomyosarcoma with osteosarcomatous differentiation of the breast is an uncommon entity. We present the case of a 37-year-old female who presented with a lump in the breast and pulmonary lesions on PET-CT, for which she underwent a toilet mastectomy. Histopathological examination revealed a tumor with cells arranged in sheets. These tumor cells had moderate eosinophilic cytoplasm, highly pleomorphic, irregular hyperchromatic nuclei, coarse chromatin, and prominent nucleoli. Areas with spindle-cell morphology were noted. Osteoid was seen intermingling with the tumor along with numerous osteoclast-like multinucleate giant cells. A wide panel of Immunohistochemistry was applied, and Desmin, h-Caldesmon, SMA, and Vimentin were positive. The patient died 3 months post-surgery and had a recurrence at the surgical site.

Utility of cytomorphology in distinguishing solid pseudopapillary neoplasm of pancreas from pancreatic neuroendocrine tumor with emphasis on nuclear folds and nuclear grooves.

BACKGROUND: Pancreatic solid pseudopapillary tumor (SPN) and pancreatic neuroendocrine tumors (Pan-NET) have close resemblance on imaging and cytomorphology, though they differ in their prognosis and treatment strategy. SPNs are low-grade indolent tumors while Pan-NETs harbor malignant potential with propensity to metastasize. We aim to differentiate SPN from Pan-NET based on cyto-morphology; to classify nuclear membrane (NM) irregularities or nuclear folds into four grades and see whether they bear any difference with respect to the two entities. METHODS: Eighteen and ten confirmed cases of SPN and Pan-NET were included in the study. Smears were assessed for architecture, background changes, cellular, and nuclear features, which were compared between the two study groups. Nuclear folds were classified into four grades. Nuclear folds and nuclear grooves were also compared between the two groups. RESULTS: All SPN patients were females; mean age of 28 years. Pan-NET patients had equal male to female ratio; mean age of 46 years. Both SPN (78%) and Pan-NET (71%) showed predilection for pancreatic head. Mean size of lesion was 4.8 cm and 3.1 cm in SPN and Pan-NET groups. Papillary pattern, branching capillaries, degenerative background were significantly more prominent in SPN; sudden anisonucleosis and cytoplasmic granularity in Pan-NET. Metachromatic matrix, hyaline globules, and nuclear grooves were noted exclusively in SPNs. Nuclear fold grades 2 and 3 were more characteristic of SPN than Pan-NET (P = 0.041 and 0.002, respectively). CONCLUSIONS: Cytomorphology is vital in differentiating SPN from Pan-NET with nuclear folds being an important nuclear feature.

Invasive cystic hypersecretory carcinoma of the breast

ABSTRACT Cystic hypersecretory carcinoma (CHC) of the breast is a rare variant of ductal carcinoma, characterized by variably sized cysts lined by micropapillary fronds to proliferative pseudostratified columnar epithelium. It includes a spectrum of morphological features ranging from clearly benign cystic hypersecretory hyperplasia (CHH), CHH with atypia to invasive CHC. Only 20 cases of invasive CHC have been reported to date. We report a case of a 49-year-old female who presented with a palpable breast lump and nipple discharge. Gross examination showed variable-sized cysts lined by solid grey white tumors. On microscopic examination, cysts were lined by micropapillary fronds with eosinophilic colloid-like secretion with a focus of invasion. A diagnosis of invasive CHC was made. Since there are limited case reports, our understanding of its biological behavior, prognostic factors, and genetic basis is limited.

Desmoplastic nested spindle cell tumours and nested stromal epithelial tumours of the liver.

Desmoplastic nested spindle cell tumour of liver (DNSTL), nested stromal-epithelial tumour (NSET) and calcifying nested stromal-epithelial tumour (CNSET) are recently described entities with similar morphology, immunohistochemistry and molecular genetics. These are rare entities with only three large case series described till date. These tumours commonly present in the paediatric age group. NSETs, in addition have been described to be associated with ectopic adrenocorticotropic hormone (ACTH) production and Cushingoid features. It is important to discuss this rare group of tumours with a low malignant potential as the most common radiological differential diagnosis is hepatoblastoma, which has a relatively poorer prognosis. Thus, a pathologist needs to keep this entity in mind, so as to offer a correct histological diagnosis.