von Meyenburg complexes are more frequently associated with cholangiocarcinoma.

AIM: There is some evidence that von Meyenburg complexes (VMCs) can progress to cholangiocarcinoma (CC). This study aimed to evaluate the prevalence of VMCs in CC cases. METHODS: All hepatic resections and explants with intra-hepatic CC (I-CC) and hilar-CC (H-CC) from 1985 to 2020 were studied. Hepatic resections (n=68) for benign lesions or metastatic colonic carcinoma and 15 cases with cirrhosis without any cancer were used as controls. RESULTS: A total of 118 cases of CC (88 I-CC, 30 H-CC) were identified. Of these, 61 (52%) patients had no known background liver disease, and 20 (17%) had cirrhosis. Associated liver disorders included metabolic dysfunction-associated steatohepatitis (23), chronic viral hepatitis B or C (13), biliary disease (primary or secondary sclerosing cholangitis) (8), polycystic kidney disease (6), cryptogenic cirrhosis (5) and others miscellaneous disorders (7). VMCs were present in 34 (39%) of 88 I-CC cases and 7 (23%) of 30 H-CC cases. VMCs were present within the tumour (20 cases), outside the cancer (21 cases) or at both locations (10 cases). VMCs with dysplasia/carcinoma in situ were seen in 19 of 41 (46%) cases with CC and VMCs. In addition, bile duct adenomas were identified in 6 (5%) of CC. 7% of controls showed the presence of VMCs compared with 35% of CC cases (p<0.05). CONCLUSIONS: VMCs are seen far more frequently in patients with CC than in the control group. The findings support the hypothesis that VMCs could represent a precursor of CC or a marker for a higher risk of developing CC.

Histopathology and its clinical correlation of liver biopsy in patients with treated autoimmune hepatitis.

The diagnosis of autoimmune hepatitis (AIH) relies on well-established criteria encompassing histological, serological, and clinical features. Diagnosing AIH may become challenging when encountering patients who have undergone steroid therapy for other co-existing diseases. Thirty-nine liver biopsies from 25 patients with treated and untreated AIH were classified into three groups: 1) Newly diagnosed untreated biopsies (n = 16); 2) Newly diagnosed partially treated biopsies from patients already on steroid treatment for other co-existing diseases (n = 9); 3) Previously diagnosed biopsies from patients who had undergone complete treatment (n = 14). In the untreated AIH group, at least 50 % of the cases exhibited the following features: at least moderate portal inflammation (81 %), at least moderate lobular inflammation (56 %), ductular reaction (94 %), inflammation gradient from bile duct to interface (88 %), unequivocal interface hepatitis (100 %), emperipolesis (56 %), plasma cell cluster (88 %), apoptosis or necrosis (63 %), pericentral inflammation (63 %), and periportal fibrosis (88 %). Although all these diagnostically sensitive histologic features were present in significantly fewer cases after treatment (p < 0.05), the features of ductular reaction, inflammation gradient from bile duct to interface, pericentral inflammation, and periportal fibrosis were likely to persist after treatment, especially in partially treated cases; these features did not show a significant association with higher transaminase levels (P > 0.05) and were considered as indirect features of hepatocytic injury. Our data suggest categorizing AIH histological features into direct and indirect hepatocytic injuries. Direct hepatocytic injury features significantly correlate with transaminase levels and respond well to treatment, while indirect ones show weaker transaminase correlation and relative treatment resistance.

Immune checkpoint inhibitor therapy associated enteritis mimicking celiac disease.

A 68-year-old man with a previous history of lung cancer presented with deteriorating appetite and weight loss. Imaging revealed significant retroperitoneal lymphadenopathy, as well as liver and bone lesions consistent with widespread metastatic carcinoma. Biopsy results from the liver lesions confirmed the diagnosis of metastatic non-small cell lung carcinoma. A PDL-1 immunostain, performed on the initial lung resection specimen, showed a combined positive score (CPS) of 15 and pembrolizumab treatment was initiated. The patient presented with diarrhea three weeks after starting therapy and duodenal biopsies obtained at this time displayed intact villous architecture with an increase in intraepithelial lymphocytes (IELs). The colon biopsies exhibited lymphocytic colitis, characterized by significant thinning of the surface epithelium, a higher mixed inflammatory infiltrate within the lamina propria, and diffuse increase of IELs (greater than 30 per 100 epithelial cells). These findings collectively raised the differential diagnosis of celiac disease with lymphocytic colitis or immunotherapy-associated enterocolitis. Further serological testing for celiac disease, including anti-tissue transglutaminase antibodies, yielded negative results. Consequently, a final diagnosis of immune adverse event associated with immunotherapy was established. Cases reported in literature as celiac disease occurring soon after immunotherapy are likely misdiagnosed cases of immunotherapy enteritis.

Histology and clinical correlations in autoimmune hepatitis, primary biliary cholangitis, and autoimmune hepatitis-primary biliary cholangitis overlap syndrome.

OBJECTIVES: The diagnosis of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and AIH-PBC overlap syndrome (OS) relies on their histologic features and clinical findings. In this study, we aimed to identify specific morphologic features of these diseases and evaluate their clinical correlation. METHODS: We included initial biopsies from untreated patients with AIH (n = 14), PBC (n = 10), and OS (n = 7). Histologic features of the portal tract, portal-lobular interface, and hepatic lobule, fibrosis, as well as clinical data including serology, autoantibodies, treatment, and prognosis were reviewed and analyzed. RESULTS: Our results showed that several histologic features differed significantly between AIH and PBC (p < 0.05). Among these features, OS cases were more likely to present with bile duct-centered processes (presence of bile duct damage while absence of inflammation gradient from bile duct to interface, plasma cell cluster and pericentral inflammation) unlike those seen in AIH (p < 0.05), and interface-centered processes (unequivocal interface hepatitis, ductular reaction, and periportal fibrosis) which were not seen in PBC (p < 0.05). We observed a significant correlation between transaminase levels and lobular inflammation, including numbers of lymphocyte, plasma cell and eosinophil. Our study also found that anti-smooth muscle antibody positivity was associated with interface hepatitis (p < 0.01), while antimitochondrial antibody positivity was associated with duct damage (including ductopenia) and granulomas (p < 0.05). CONCLUSION: Our results highlight distinctive morphological features between AIH and PBC. The possibility of overlap syndrome should be considered when encountering AIH with bile duct-centered processes or PBC with interface-centered processes in morphology and correlation with autoantibodies.

Lymphoepithelioma-like neoplasm of the biliary tract with 'probable low malignant potential'.

AIMS: Lymphoepithelioma-like carcinomas (LELCs) are uncommon epithelial cancers characteristically showing two distinct components consisting of malignant epithelial cells and prominent dense lymphoid infiltrate. Hepatic LELCs consist of two types, the lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like cholangiocarcinoma (LEL-CCA), with the latter being strongly associated with Epstein-Barr virus (EBV). METHODS AND RESULTS: We present a series of three cases of intrahepatic biliary EBV-associated LEL tumours in which the biliary epithelial component showed a distinctly benign appearance, instead of the usual malignant epithelial features of a typical CCA or EBV-associated LEL-CCA. In the lesions, the biliary epithelium showed interconnecting glands or cords of cells. All had a very low proliferation (Ki-67) index. Immunohistochemistry for IDH1 and TP53 performed on two cases was negative and molecular tests for EGFR and KRAS gene mutations performed on one were negative. Prognosis was very good in all three cases, with patients alive with no evidence of disease 24-62 months after surgery. Intriguingly, all three cases had co-infection of HBV and EBV. These cases are also discussed in the context of the 63 cases of LEL-CCA available in the literature, with a focus on epidemiology, clinicopathological features and potential research interests. CONCLUSIONS: Based on the distinct clinicopathological features and unique survival benefits, we believe these tumours represent the benign end of the spectrum of EBV-associated lymphoepithelial biliary carcinomas. Whether these tumours require a revision of the current nomenclature to 'lymphoepithelioma-like neoplasm of the biliary tract with probable low malignant potential' will require more detailed analysis with larger case-series.

Recurrent Adult Sacrococcygeal Teratoma Developing Adenocarcinoma: A Case Report and Review of Literatures.

Sacrococcygeal teratomas (SCT) are most commonly seen in infants and children but are rare in adults. Most adult SCT are benign and mature with a minority of tumors having immature components or overt malignancy. Here, we report a 65-year-old female with a SCT developing adenocarcinoma. The patient was diagnosed with benign sacrococcygeal cystic teratoma on her initial hospital visit and was treated with surgical resection. She was followed up postoperatively and was noted to have a markedly elevated CA 19-9 level 13 months after the surgery. Radiological and clinical examination revealed thickening of the perirectal soft tissues, located near the inferior portion of her previous incision site. Histological evaluation of the lesion showed invasive, moderately differentiated adenocarcinoma. Immunohistochemical staining results were suggestive, but not diagnostic, of anal gland adenocarcinoma. This case report expands the knowledge regarding an adenocarcinoma arising from a previously benign, adult SCT.

Ultrasound-guided fine needle aspiration cytology of angiosarcoma of head and neck: a review of cytomorphologic features and discussion of diagnostic pitfall of aspiration cytology of vascular lesions.

Angiosarcoma is a rare malignant tumor of vascular origin (<2% of sarcomas). It represents <1% of all head-neck malignancies. A cytological diagnosis on fine needle aspiration (FNA) is extremely difficult. Most tumors yield a predominantly hemorrhagic aspirate with only rare neoplastic cells, a diagnostic pitfall of aspiration cytology of vascular lesions. An 81-year-old male, 2 years status post resection of a nasal tip angiosarcoma and adjuvant radiation therapy, presented to another institution with an enlarging left neck mass of 2 months duration. Outside FNA diagnosis of cyst was made. Patient was referred to our institution for a pathologist-performed ultrasound-guided FNA. Ultrasound examination revealed a hypoechoic cystic left neck mass. Direct smears showed blood with occassional single malignant spindled to epithelioid cells, with some cells showing "spider-leg" like cytoplasmic processes/projections and "tadpole/fiber" like morphology. Immunohistochemistry performed on cell block sections revealed the tumor cells to be positive for D2-40, CD31 and CD34, supported a diagnosis of regional recurrent angiosarcoma. Left neck dissection showed recurrent high-grade angiosarcoma infiltrating periparotid soft tissues and metastatic angiosarcoma involving multiple lymph nodes. A diagnosis of angiosarcoma on FNA samples can be challenging, as the aspirate may contain only rare tumor cells hidden in a background of abundant blood. Such cases require careful screening to avoid an incorrect diagnosis of inadequate or cyst contents. This short review highlights key cytomorphologic features of angiosarcoma, includes novel cytologic features of angiosarcoma which has not been described previously and also discusses challenges and diagnostic pitfalls of FNA of vascular lesions.

A Case of Sudden Death: Subarachnoid Hemorrhage, Pheochromocytoma, Berry Aneurysm.

Subarachnoid hemorrhage is a medical emergency. Berry aneurysm rupture is the second most common cause following trauma. Diagnosis is often challenging. Neurogenic heart syndrome often complicates subarachnoid hemorrhage. A concomitant pheochromocytoma can be deadly causing sudden cardiac arrhythmia. Here, we describe a case of subarachnoid hemorrhage with concomitant incidental pheochromocytoma in a relatively young female who died suddenly, diagnosed during autopsy. A 57-year-old Hispanic woman with past medical history of asthma, prediabetes, and uncontrolled hypertension collapsed unexpectedly. She initially had ventricular tachycardia, followed by pulseless electrical activity and finally asystole without response to resuscitation. In the emergency department she was on epinephrine, calcium, naloxone, and tPA with suspected thrombotic stroke. Despite measures, she was pronounced dead. Autopsy revealed subarachnoid hemorrhage due to a ruptured berry aneurysm. Additionally, pheochromocytoma was detected in the right adrenal gland. Subarachnoid hemorrhage has a grave prognosis by itself. This case describes the uncommon detection of pheochromocytoma in the setting of subarachnoid hemorrhage.

Cutaneous Angiomyolipoma of the Ear: A Case Report and Literature Review.

Cutaneous angiomyolipoma is a rare mesenchymal tumor, distinct from its renal counterpart. Only few cases have been reported in English language literature to date. Here, we report a case in a 36-year-old man who presented with a painless swelling on his right ear. Microscopy revealed a well-circumscribed tumor, composed of an admixture of mature adipocytes, blood vessels, and bundles of smooth muscles. The tumor cells were positive for desmin and calponin but negative for HMB45, melan-A, SOX10, tyrosinase, and CD10. We present the case to emphasize the uniqueness of cutaneous angiomyolipoma from its renal counterpart. We also review the relevant literature on this topic.

The outlet patch: gastric heterotopia of the colorectum and anus.

AIMS: Gastric heterotopia (GH) has been described throughout the gastrointestinal tract. However, the colorectal region is an extremely rare location for it. We describe the clinicopathological features of GH of the colon, rectum and anus. METHODS AND RESULTS: We identified 33 cases in 20 males and 13 females (median age = 54 years; range = 4 months-73 years). Sites included the rectum (n = 26), anus (n = 4), ileocaecal junction (n = 1), ascending colon (n = 1) and descending colon (n = 1). Presenting symptoms (n = 27) included haematochezia (41%) and altered bowel habits (4%); 15 patients (55%) were asymptomatic. On colonoscopy (n = 31), all appeared as solitary lesions (median size = 6.5 mm, range = 2-55 mm), either as polyps (61%), raised erythematous patches (23%), an ulcer (10%), within a rectal diverticulum (3%) or a haemorrhoid (3%). Patients were managed by polypectomy. One with an associated carcinoma in the area of GH underwent resection. No morbidity related to GH itself was reported following excision. Histologically, heterotopic gastric mucosa was oxyntic (85%), mixed oxyntic and non-oxyntic (12%) and not specified (3%) types. In five patients a pyloric gland adenoma (PGA) arose from heterotopic gastric mucosa, two of which contained a focus of invasive adenocarcinoma. One case had associated surface foveolar-type low-grade dysplasia. Another had associated adenocarcinoma arising from the heterotopic mucosa. One example harboured Helicobacter pylori organisms. CONCLUSIONS: We highlight the features of GH in the distal GIT - the 'outlet patch'. Association with PGA, surface dysplasia and adenocarcinoma suggests that lower tract GH can undergo neoplastic transformation.

Spectrum of findings in orchiectomy specimens of persons undergoing gender confirmation surgery.

Gender confirmation surgery is increasingly common in persons with gender dysphoria. We describe changes seen in gonads from individuals seeking male-to-female physical adaptation. We studied 99 orchiectomies from 50 persons. The average age was 33 years (range, 21-63 years). Eighty-six (86.8%) of 99 testes were normal in size with an average size of 3.87 cm (range, 3.0-5.5 cm). Thirteen (13.1%) of 99 testes were hypotrophic and measured up to 2.5 cm. Seminiferous tubules were reduced in diameter compared with controls (0.137 mm versus 0.237 mm; P < .001) and showed peritubular fibrosis in 41 (82%) of 50 persons. In 40 (80%) of 50 persons, there was maturation arrest at the spermatogonia level. In 10 (20%) of 50 persons, the seminiferous tubules showed focal spermatids/spermatozoa up to 7 per 10 tubules mixed with partial maturation arrest at primary spermatocytes. Twenty-six (26%) of 99 testes showed seminiferous tubules with rare cells with large nuclei (3× size of Sertoli cells nuclei) and degenerative chromatin (cytomegaly). Leydig cells were absent in 50 (50%), markedly reduced in 30 (30%), and similar to controls (mean, 33/high-power field) in 20 (20%). A subset (20/99; 20%) of testes had epithelial hyperplasia of the proximal epididymis with stratification and micropapillae. There was no germ cell tumor, sex cord stromal tumors, or germ cell neoplasia in situ. In summary, the histologic changes include (1) decreased diameter of seminiferous tubules and expansion of the interstitium, (2) marked hypoplasia of germ cells, (3) rare cytomegaly, (4) hypoplasia or absence of Leydig cells, and (5) epididymal hyperplasia.

Primary Paediatric Renal Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature.

Ewing sarcoma/primitive neuroectodermal tumor (PNET) is a high-grade malignant neoplasm commonly affecting bones of the thoracic region. Primary Ewing sarcoma/PNET of the kidney is exceptional; it commonly affects young adults and is rarely reported in children. Here we describe a case of renal PNET in a 10-year-old girl who presented at our institute with haematuria and abdominal lump. Computer tomography scan revealed a huge mass in the right kidney. Computer tomography-guided aspiration from the mass showed cytomorphological features of a small blue round cell tumor. The patient underwent right radical nephrectomy. Histopathology with supplementary immunohistochemistry confirmed the diagnosis of PNET. She has been receiving treatment with adjuvant chemotherapy post-surgery and is currently disease free. Primary renal PNET is a distinct and rare entity. This tumor is very aggressive with low survival rate, even with a multi-disciplinary approach. We reported the case because it is rare in children, poses diagnostic challenges, is aggressive in behaviour and responds poorly to treatment.

Preoperative Ultrasound Guided Fine Needle Aspiration Cytology of Ovarian Lesions- Is It a Rapid and Effective Diagnostic Modality?

INTRODUCTION: The deep seated ovarian lesions unapproachable by unguided aspiration cytology were easily done under ultrasound guidance. It gave a before hand cytological diagnosis of the lesion to the surgeon determining the modality of treatment for the patient. AIM: To find the diagnostic accuracy of the method of ultrasound guided cytological assessment of ovarian lesion. MATERIALS AND METHODS: The study was conducted as a prospective observational study over a period of one year, in hospital setting, where ultrasound guided fine needle aspiration had been used to aspirate ovarian lesions, giving a rapid cytological diagnosis. In 43 sample cases, aspiration of fluid done from ovarian lesions were followed by cyto-centrifugation and staining by May-Grunwald-Giemsa (MGG) and Papanicolaou (Pap) stain providing a cytological opinion regarding benign/malignant nature of the lesion and further categorization. Later the cytological diagnosis was compared with final histopathological diagnosis, taking it as a gold standard. RESULTS: The overall sensitivity, specificity, and diagnostic accuracy of ultrasound guided aspiration and cytological analysis were high, 96%, 76.92% and 89.47% respectively as calculated by comparing the cytological diagnosis with histological diagnosis, taking it as gold standard. CONCLUSION: This method has evolved as a highly sensitive, rapid, simple and effective modality for screening and as well as accurate preoperative diagnosis of ovarian lesions.

Ectopic Paratubal Adrenal Cell Rest Associated with Mucinous Cystadenoma of Ovary.

Ectopic adrenal cortex is a rare entity. Usually found in male children; commonly located around kidney, retroperitoneum, spermatic cord and para-testicular region. Rarely, adults with heterotopic adrenal glands are described. Incidence in females is very less; though sometimes detected accidentally in hysterectomy specimens. We describe a case of ectopic adrenal cortical cell in paratubal region in a patient with mucinous cyst adenoma of ovary. A 26-year-old female presented with complains of menstrual irregularities and abdominal discomfort for 6 months. Investigations suggested a right ovarian cyst. Right ovarian cystectomy with partial salpingectomy was performed; histopathology revealed mucinous cyst adenoma. Sections from tube showed presence of ectopic adrenal cortical rest in the paratubal region, incidentally discovered on microscopy. We present this case because of its rarity in females, interesting presentation with another unrelated gynaecological pathology, its potentiality for malignant transformation and possible complications.

Tumour morphology after neoadjuvant chemotherapy as a predictor of survival in serous ovarian cancer: an experience from a tertiary care centre in India.

Serous ovarian cancer is the most common malignant ovarian tumour. Traditional management consists of surgical resection with postoperative chemotherapy. Currently neoadjuvant chemotherapy is offered to patients with advanced stage disease. The present study aims to analyse the histomorphological alterations in serous ovarian cancer following neoadjuvant chemotherapy. Correlation of these morphological alterations with survival is also presented here. Serous ovarian cancers from 100 advanced stage cases were included; 50 were treated with pre-surgery chemotherapy. Semi-quantitative scoring was used to grade the alterations in tumour morphology. Survival data was correlated with the final morphological score. Tumour morphology was significantly different in cases treated with neoadjuvant chemotherapy (CT group) as compared to cases with upfront surgery. The CT group cases showed more fibrosis, calcification, and infiltration by lymphocytes, plasma cells, foamy and hemosiderin-laden macrophages. The residual tumour cells had degenerative cytoplasmic changes with nuclear atypia. Patients with significant morphological response had a longer median survival, although it did not attain statistical significance in the current study. With the increasing use of neoadjuvant chemotherapy in management, the pathologist needs to be aware of the altered morphological appearance of tumour. Further studies are required to establish a grading system to assess the tissue response which can be helpful in predicting the overall therapeutic outcome and the prognosis of patients.

Giant Cell Tumour of Soft Tissue in Neck: An Uncommon Tumour in an Uncommon Location.

Giant cell tumour of soft tissue is an extremely rare tumour. It is thought to be the soft tissue counterpart of giant cell tumours of the bone due to its histological and immunohistochemical resemblances. Almost 80% of these tumours occur in upper and lower extremities; neck is a very rare location. Here we describe a case of primary soft tissue giant cell tumour in right submandibular region. A 35-year-old male patient presented with a swelling in right submandibular area. FNAC suggested a benign soft tissue neoplasm, comprising of spindle cells and multinucleated giant cells. Histopathology of resected specimen showed spindle cell tumour with intricately mixed giant cells, consistent with a primary giant cell tumour of soft tissue. Giant cells were CD 68 positive. Giant cell tumour of soft tissue is benign tumour, though very rarely can show features of malignancy. We present this case for its rarity and morphological overlap with other soft tissue neoplasms containing giant cells.

Retroperitoneal giant ancient schwannoma.

Ancient schwannoma is a rare variant of benign peripheral nerve sheath tumor, often morphologically mimicking malignancy. Retroperitoneum is an uncommon location. We describe one case of giant retroperitoneal ancient schwannoma. Literature concerning this variant is also reviewed. A 65 year old male presented with altered bowel habits. Imaging findings revealed a large heterogeneous mass in the retroperitoneum. The patient was treated with complete excision. Grossly, the tumor was predominantly solid with focal cystic degeneration. Histological examination showed an encapsulated spindle cell tumor with nuclear palisading, very focal nuclear atypia and widespread foam cell infiltration - findings consistent with ancient schwannoma. A diagnosis of ancient schwannoma can be considered for a solid-cystic encapsulated mass in the retroperitoneum. Malignant transformation is very rare. Local recurrence is uncommon following complete excision. The authors have nothing to disclose.

Primary renal synovial sarcoma: a rare tumor with an atypical presentation.

Primary renal synovial sarcoma (PRSS) is a very rare tumor, first described by Argani, et al. The exact incidence of PRSS is not yet known. Here we present a case of PRSS diagnosed by histopathology, supplemented with immunohistochemistry.

Tissue biomarkers in prognostication of serous ovarian cancer following neoadjuvant chemotherapy.

Serous ovarian cancer (SOC) is a significant cause of morbidity and mortality in females with poor prognosis because of advanced stage at presentation. Recently, neoadjuvant chemotherapy (NACT) is being used for management of advanced SOC, but role of tissue biomarkers in prognostication following NACT is not well established. The study was conducted on advanced stage SOC patients (n = 100) that were treated either conventionally (n = 50) or with NACT (n = 50), followed by surgery. In order to evaluate the expression of tissue biomarkers (p53, MIB1, estrogen and progesterone receptors, Her-2/neu, E-cadherin, and Bcl2), immunohistochemistry and semiquantitative scoring were done following morphological examination. Following NACT, significant differences in tumor histomorphology were observed as compared to the native neoplasms. MIB 1 was significantly lower in cases treated with NACT and survival outcome was significantly better in cases with low MIB 1. ER expression was associated with poor overall survival. No other marker displayed any significant difference in expression or correlation with survival between the two groups. Immunophenotype of SOC does not differ significantly in samples from cases treated with NACT, compared to upfront surgically treated cases. The proliferating capacity of the residual tumor cells is less, depicted by low mean MIB1 LI. MIB 1 and ER inversely correlate with survival.