Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Chondromyxoid Fibroma (CMF) is an uncommon non malignant cartilage tumour with a greater predilection for the legs, with about a quarter of cases involving the metatarsals. It accounts for less than 0.5% of all bone tumours and mostly occurs in patients aged 10 to 30 years old. Patients typically present with complaints of pain and swelling in the affected region. Radiologically, a lytic lesion with well-defined margins is observed in the metaphysis. The present case is about an 11-year-old male who presented to the Orthopaedic Outpatient Department (OPD) with a history of pain and swelling over his left foot. Upon examination, a discrete swelling was noted over the lateral aspect of the foot, extending from the head to the shaft of the 4th metatarsal. Upon palpation, the swelling was found to be tender and firm in consistency, accompanied by restricted foot movement. Initially, a giant cell tumour of the 4th metatarsal bone in the left foot was suspected based on radiography. However, histopathological examination led to the diagnosis of CMF. The lesion was curetted, and a below-knee Plaster of Paris (POP) was applied for one month. No recurrence of the lesion has been observed after five months of follow-up.

Gynandroblastoma is a rare mixed sex cord stromal tumor of ovary. These tumors contain both granulosa cell component and Sertoli-leydig cell component. Very few cases of Gynandroblastomas are reported in literature. Reported cases are accompanied by estrogenic, androgenic or no harmone effects. This is a case of Gynandroblastoma reported in 18 year old female with history of pain abdomen, spotting per vaginum, significant weight loss since 3 months. The tumor diagnosis is based on histopathological features.

Immunoproliferative small intestinal disease (IPSID) is a rare type of indolent B-cell lymphoma. It is a variant of extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue. It is commonly seen in older children and young adults in the age group of 10-35 years. It is more common in males with Male: Female ratio of 2.4:1. Duodenum and jejunum are the commonly involved areas in small intestine. Colicky abdominal pain and intermittent diarrhoea are the common symptoms. Here by, we report a rare case in a 74-year-old male patient presented with chief complaints of abdominal pain, diarrhea and weight loss for 3 months. CT scan findings revealed thickening of small intestinal wall and mesenteric lymphadenopathy. Upper gastrointestinal endoscopy findings revealed nodular and ulcerative mucosa in the duodenum. Histopathological examination revealed flattening of mucosa with villous atrophy, destruction of crypts and intraepithelial lymphocytic infiltrate is noted. Interstitium shows dense and diffuse collection of lymphoplasmacytic infiltrate. Immunohistochemistry was done and it showed CD20 positive lymphoid cells. Based on the above findings the case was reported as Immunoproliferative small intestinal disease. Clinicians should suspect IPSID in cases presenting with chronic diarrhea and abdominal pain refractory to treatment. Immunoproliferative small intestinal disease has indolent clinical course and it can be cured with antibiotics in early stages. Late stages have high mortality rate and has poor prognosis. Keywords: IPSID, Alphachain disease, B cell lymphoma, duodenum, villous atrophy, lymphoplasmacytic infiltrate

Multilocular cystic renal cell carcinoma or multilocular clear cell renal cell carcinoma is a rare type of cystic neoplasms of kidney. MCRCC comprises 1-2% of all renal tumors. MCRCC has well defined diagnostic criteria, has low stage The term MCRCC was renamed as MCRNLMP by ISUP in 2013.Only few cases of MCRCC are reported in literature till now We report a rare case of MCRCC / MCRNLMP in 52 years female presented with chief complaints of pain and dragging sensation in the right side of abdomen for 1 year. Keywords: Multilocular, cystic, renal cell carcinoma, nephrectomy, low malignant potential

The clinical significance of the tumor‐immune interaction in breast cancer is now established, and tumor‐infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple‐negative (estrogen receptor, progesterone receptor, and HER2‐negative) breast cancer and HER2‐positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state‐of‐the‐art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false‐positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in‐depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple‐negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector‐based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well‐described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.

Introduction: Pancreatic mixed neuroendocrine non-neuroendocrine neoplasms are extremely rare tumours accounting for 0.5% of all the pancreatic malignancies and 5% of all pancreatic neuroendocrine neoplasms. These tumors are rarely diagnosed preoperatively and they have a poor prognosis. Pancreatic MiNEN is characterized by 2 malignant lesions adenocarcinoma and Neuroendocrine tumour with each constituent involving more than 30% of the tumour. We report a case of 57yr old male with dullaching abdominal pain radiating to back. CA 19-9 was mildly elevated. Other laboratory tests are within normal limits. CECT abdomen revealed bulky pancreas with specks of calcification in the head of the pancreas and few tiny non enhancing hypodense areas and a well defined isodense lesion measuring 1.2x1.4cm in the second part of duodenum with enhancement in post contrast images associated with thickness of duodenal wall. The patient underwent Whipple’s pancreaticoduodenectomy with regional lymphadenectomy. Histopathological examination of specimen revealed an infiltrating acinar adenocarcinoma of the pancreas interspersed with a well differentiated neuroendocrine tumour component which made up of more than 45% of the tumour. The features were consistent with Mixed Neuroendocrine Non Neuroendocrine Neoplasm of the pancreas. Keywords: MiNEN, Pancreas, Neuroendocrine, Non neuroendocrine, Adenocarcinoma

Primary thyroid lymphoma accounts for 5% of all the malignancies of the thyroid gland. The thyroid is very rare and unusual site for lymphoma, only few cases have been described in the literature. It is associated with chronic inflammatory lesions such as chronic lymphocytic thyroiditis. We report a rare case of Marginal Zone lymphoma in a 44 year old male patient presented with complaint of swelling in the right side of neck since 3 months. The definitive diagnosis was confirmed by histopathological examination and immunohistochemistry.

Chondrosarcomas and Chordomas account for the majority of primary skull base tumors, which are slow growing and locally aggressive. These tumors cause severe cranial nerve neuropathies. Both these tumors have similar clinical, radiological, and histological resemblances. Histopathology, along with immunohistochemistry, helps to differentiate these tumors. We are presenting a case of 39year old female who came with double vision, squint, headache, and tingling sensation over the right side of the face. Examination and investigations concluded a skull base tumor near the cavernous sinus. Surgical resection of the lesion was done and sent for histopathology. Microscopy showed hyaline cartilaginous islands, myxoid matrix, and individual cells with vacuolated cytoplasm and ovoid nucleus. Immunohistochemistry showed positive for S100. Final diagnosis of low-grade Chondrosarcoma was made. Keywords: Chondrosarcoma, Skull base tumors, Chordoma, S100

Expression of Her2/neu in Urothelial Neoplasms and its Association with Histopathological Prognostic Parameters

Giant condyloma is a rare and sexually transmitted disease which is characterized by solitary pink or red raised lesions affecting mucosal surface of anogenital regions. Condylomas may also develop in extragenital sites. Diagnosis of genital condyloma is simple whereas extragenital condyloma is challenging. Here we present a case in a 64year old man with history of psoriasis, presenting with extragenital giant condyloma in the gluteal region.

Rosai-Dorfman disease is a rare, idiopathic, benign, histiocytic proliferation, usually seen in children and younger adults. Most common site of involvement is cervical lymph node. However, extra nodal manifestations are seen in significant proportion of cases.This case report discusses the unusual presentation of Rosai-Dorfman disease as mass lesion involving bilateral nasal cavities, paranasal sinuses and orbit along with multiple deposits in dura and cervical lymph node.

Congenital cystic adenomatoid malformation (CCAM) is a rare entity with unexplained cause that effects the distal bronchi. It accounts for 25% of congenital pulmonary malformations with surgical excision as the treatment of choice. The mortality rate of patients with CCAM ranges from 9 to 49% if diagnosed prenatally. The outcome of a patient mainly depends on the presence of hydrops foetalis, microscopic type of CCAM, and the size of the lesions. The mainstay treatment of CCAM is surgical excision of the lesion which prevents complications of repeated infections, pneumothorax, and malignancy. We present 2 cases one is 5-month-old male child and other 8-month female child admitted to hospital with shortness of breath and poor suckling who was evaluated for respiratory distress. Clinically diagnosed as pneumonia, CT chest showed a cystic malformation in right lower lobe of lung and excision was done. Specimens were sent for histopathological examination and was diagnosed as congenital cystic adenomatoid malformation. Keywords: congenital cystic adenomatoid malformation, infant, lobectomy

Tuberculosis is an infectious disease primarily affecting lungs and also involves any body organ. Intracranial tuberculosis constitutes about 0.15-5% of all intracranial space-occupying lesions. Pituitary gland as primary site for tuberculosis is very rare. Delayed diagnosis and treatment can result in permanent endocrine dysfunction. Here we present a case in a 44-year-old female presented to the hospital with complaints of progressive worsening headache, left eye pain, and blurred vision for 6 months. Patient was evaluated and radiological workup was done. MRI brain with contrast showed enhancing mass lesion of 1.7x1.4 cm arising from Sella with mass effect on optic chiasma and it was radiologically diagnosed as pituitary adenoma. A biopsy from the pituitary region was obtained and histopathological examination was done. Microscopic examination revealed pituitary gland parenchyma showing well-formed epithelioid granulomas consisting of epithelioid cells, Langhans type of giant cells, and chronic inflammatory cells along with foci of caseous necrosis. The case was finally diagnosed as pituitary tuberculoma. Keywords: Tuberculosis, granuloma, space-occupying lesion, pituitary gland.

Renal angiomyolipoma is a benign mesenchymal neoplasm of kidney and composed of varied proportions of adipose tissue, smooth muscle cells- spindled or epithelioid and dysmorphic thickened or hyalinised blood vessels. Epithelioid angiomyolipoma is one of the rare variants of angiomyolipoma with high degree of complications, recurrence and metastasis. Whereas classic angiomyolipoma does not show metastasis and recurrence. Giant epithelioid angiomyolipoma means tumor size measuring greater than10 cm, very few cases have been reported in literature. Epithelioid angiomyolipoma of size greater than 20 cm is extremely rare. Here we report a rare case of giant epithelioid renal angiomyolipoma of size greater than 20 cm in a 21-year-old female, presented with complaints of right flank pain and hematuria. The patient underwent nephrectomy with probability of malignancy given in ultrasonography and specimen was sent for histopathological examination. Gross examination revealed enlarged kidney of size 22×18×10 cm and cut section shows grey white to yellow lesion measuring 21×17×10 cm almost occupying entire kidney. Microscopic examination revealed interlacing fascicles of spindle cells, lobules of adipocytes and thickened blood vessels. Foci of pleomorphic epithelioid cells with illdefined cell borders, pleomorphic vesicular nucleus and prominent nucleoli are noted. Keywords: Epithelioid, angiomyolipoma, mesenchymal, giant, kidney

Introduction: Brain lesions can be caused by varied etiological factors like neoplastic, infectious, inflammatory and vascular diseases. Accurate diagnosis in very important for correct neurosurgical treatment. A retrospective histopathological study of brain lesions is of utmost importance because as it can demonstrate the changes in the spectrum of brain lesions,burden of disease in the community, can reveal the possible risk factors and can suggest probable treatment methods for various neoplastic and non neoplastic brain lesions. Aim: To evaluate the incidence, age distribution, gender distribution, and histopathological spectrum of neoplastic and non neoplastic lesions of brain. Materials and Methods: This retrospective study was conducted in the Department of Pathology at Narayana Medical College, Nellore, Andhra Pradesh, India, from January 2019 to December 2021. Total 216 cases were studied. The tumours were classified under World Health Organization (WHO) classification. To test the mean difference between the groups, Independent sample t-test was done. Results: Out of 216 cases, 180 (83%) were neoplastic and 36 (17%) were non neoplastic lesions. The male: female ratio was 1.03:1. Non neoplastic lesions were common in males (22, 61.11%), while neoplastic lesions were common in females (92, 51.11%). The most common age group affected was 41-50 years (55, 25.46%). Astrocytoma (41, 22.77%) followed by meningioma (40, 22.22%) were the common neoplastic tumours and haematoma(7, 19.44%) was the most common non neoplastic lesion in adults. Common tumour in children (<18 years) was diffuse fibrillary astrocytoma (3/11, 27.27%)and chronic inflammatory pathology was the common non neoplastic lesion (2/11, 18.18%). Conclusion: Majority of cases were seen in 41-50 years age group. Astrocytoma was the common neoplastic tumour and haematoma was the common non neoplastic lesion in adults. Diffuse fibrillary astrocytoma was the common tumour and chronic inflammatory pathology was the common non neoplastic lesion in children.

Background: Histopathological examination of prostatic specimen is gold standard for the diagnosis of prostate cancer. Current study evaluates the expression of AMACR and p63 in the prostate lesions using AMACR and p63 cocktail. Materials and Method: Total of 180 cases were collected and Haematoxylin and Eosin staining performed followed by immunohistochemical analysis using AMACR and p63 antibody. Result: Out of 180 cases, Benign Prostatic Hyperplasia is the most common lesion noted in about 120 cases. In this study, the predominant population was in the 6th to 7th decade of age. Most of the patients presented with difficulty in micturition. Immunohistochemistry revealed that p63 expression is positive in all normal basal cells, 118 cases (98.33%) were negative for AMACR and only 2 cases were showing focal and weak AMACR immunoreactivity. AMACR was positive in all the 6 HGPIN cases with variable intensity. Out of 5 LGPIN cases AMACR was positive in 3 cases with low intensity, remaining 2 cases shows AMACR negative. p63 is positive in all 11 PIN cases (LGPIN & HGPIN) showing discontinuous staining pattern. All 22 cases of Prostatic adenocarcinomas were negative for p63 and all cases expressed positive immunostaining with AMACR. A diagnosis of adenocarcinoma was made in 48% of atypical cases. Cases which were negative for both AMACR and p63 were diagnosed as Atypical Small Acinar Proliferation, for which further follow-up is required. Conclusion: AMACR/p63 Cocktail antibody is very much useful as it saves time, tissue and is cost-effective.

Background: Synovial sarcoma is a translocation-associated mesenchymal neoplasm that represents around 10% of all soft tissue sarcomas. Diagnosing biphasic synovial sarcoma is generally straight forward, owing to distinctive histologic features. Transducer-like enhancer of split 1 (TLE1) is overexpressed in synovial sarcomas. Study aimed to evaluate sensitivity and specificity of TLE1 immunohistochemical expression in synovial sarcoma and its histological mimics. Methods: Conventional sections from 30 cases of synovial sarcoma, 24 cases of monophasic synovial sarcoma mimics and 6 cases of poorly differentiated sarcoma mimics were subjected to TLE1 IHC staining. TLE1 immunostaining was graded from 0, 1+, 2+, 3+, with 2+ or 3+ grades interpreted as positive staining. Results: Of the 60 tumours, majority are monophasic spindle cell type (56.6%), followed by biphasic (16.6%), monophasic epithelial (6.6%), poorly differentiated (13.3%) and calcifying type (6.6%). Upon expression of TLE1 in tumors, 20 cases showed Grade 3, 8 cases shown Grade 2, 2 cases shown Grade 1 TLE1 Expression in Synovial sarcoma. 2 cases shown Grade 3 and 2 cases shown Grade 2 TLE1 expression in Schwannoma. Whereas 1case shown grade 2 in Rhabdomyosarcoma. 1case shown grade 2 in Hemangiopericytoma. TLE1 sensitivity for diagnosis of synovial sarcomas was 93.3%, and specificity of 73.3% with positive predictive value of 77.77% and negative predictive value of 91.6%. Conclusion: Specificity can be increased with optimal IHC panel which includes BCL2, Pan Cytokeratin, EMA, CD99 and CD34. Molecular confirmation is the diagnostic gold standard for synovial sarcoma, TLE1, in view of its high sensitivity may be a useful marker within the optimal IHC panel for substantiating a diagnosis of synovial sarcoma. Awareness of TLE1 expression in other tumours and its correct interpretation are necessary.

Aims: Diagnosis of prostatic carcinoma is based on histomorphological features. However, sometimes this can be challenging. In such situations immunohistochemistry can be a useful adjunct. This study is aimed to evaluate such suspicious or atypical cases by using PIN4 cocktail antibody (AMACR+p63+CK5/14). Materials and methods: The present study was prospectively conducted at Upgraded Department of Pathology, Osmania general hospital, Hyderabad, Telangana state, India from August 2013 to July 2016. All hematoxylin and Eosin slides of prostatic specimens received during this period were routinely analyzed and cases with suspicious foci were subjected to immunohistochemistry. Immunohistochemistry was performed to look for expression of AMACR/p63/CK5/14 by using PIN4 Cocktail antibody. Observation and results: Out of 306 prostatic specimens, 210 cases were Benign, 36 were malignant, 16 were PIN and 44 cases showed suspicious foci and these cases subjected to PIN4 cocktail antibody. Cases with p63+/CK5/14+/AMACRwere considered as benign, cases with p63-/CK5/14-/AMACR+ were considered as malignant, cases with p63+/CK5+/CK14+/AMACR+ were considered as Prostatic intraepithelial neoplasia (PIN)/Atypical adenomatous hyperplasia(AAH),cases with p63-/CK5/14/AMACRwere considered as Atypical small acinar proliferation (ASAP). Conclusion: Immunohistochemistry can be useful adjunct to biopsy. It reduces the chance of overdiagnosis of benign lesions as malignant, and under diagnosis of malignancies as benign. Also reduces the chances of unnecessary re-biopsy.