Nodular Hyperplasia Research Articles

Hepatic and perihepatic PEComas: A study describing a series of five rare cases.

Perivascular epithelioid cell tumors (PEComas) encompass a group of rare mesenchymal neoplasms, with dual melanocytic and muscular differentiation. Hepatic PEComas are rare and difficult to diagnose, and their behavior is still unclear. Herein, we report a total of five cases of hepatic and perihepatic PEComas over a period of the last 5 years from our and collaborating center's archive. A detailed histological evaluation was done. A comprehensive panel of immunohistochemical stains was used and fluorescence in-situ hybridization analysis was performed for the TFE3 gene using break-apart probes. All these patients were women, with an average age of presentation of 44 years. The lesions were in the right hepatic lobe: three cases, the left hepatic lobe: one case, and gastrohepatic ligament: one case. The preoperative clinicoradiological diagnoses were hepatocellular carcinoma (HCC), focal nodular hyperplasia, hemangioma, metastasis, and gastrointestinal stromal tumor, respectively. Surgical excision was performed in four cases with no further adjuvant therapy. Histopathological examination and subsequent immunophenotyping revealed a diagnosis of PEComa. Fluorescence in-situ hybridization analysis was performed for TFE3 gene rearrangement in four cases. This series highlights the fact that accurate histological diagnosis of hepatic or perihepatic PEComas is important to prevent unnecessary aggressive treatment, unlike primary hepatocellular carcinomas or hepatoid/epithelioid metastatic tumors.

The Role of P4HB and SOX4 in Prostatic Carcinoma and Their Clinical Significance.

Prostatic adenocarcinoma (PAC) is the second most prevalent cancer and the fifth leading cause of cancer death in men worldwide. Additionally, pathologists may face problems diagnosing it reliably and may need more than one marker. Thus, the search for new immunohistochemical biomarkers becomes mandatory. This study aims to investigate P4HB and SOX4 expression in prostatic carcinoma, their possible roles, and clinical significance. This retrospective study included fifty-six cases of PAC and an equal number of nodular prostatic hyperplasia (NPH) that were immunohistochemically stained by P4HB and SOX4. The results of expression were compared between PAC and NPH cases, followed by correlations with available clinicopathological parameters. There was a highly significant difference between PAC and NPH regarding P4HB and SOX4 expressions in favor of PAC (both P<0.001). ROC curve analysis of the diagnostic power of P4HB showed 79% sensitivity, 76% specificity, and an area under the ROC curve of 0.845, while SOX4 showed (89%, 100%, and 0.946, respectively). P4HB and SOX4 expression showed a direct correlation (P<0.001). Moreover, the H-score of SOX4 expression showed a significant inverse relation with ERG expression (P=0.047). There was a significant correlation between P4HB and SOX4 and Gleason score (P<0.001). Moreover, P4HB expression was significantly associated with lymphovascular invasion (P=0.013), while SOX4 expression showed a significant association with perineural invasion (P=0.05). SOX4 and P4HB seem to have diagnostic and prognostic value in PAC. While there was a direct correlation between SOX4 and P4HB, an inverse relationship between SOX4 and ERG was detected.

A comparison of the performance of 68Ga-Pentixafor PET/CT versus adrenal vein sampling for subtype diagnosis in primary aldosteronism.

To investigate the diagnostic efficiency and prognostic value of 68Ga-Pentixafor PET/CT in comparison with adrenal vein sampling (AVS) for functional lateralization in primary aldosteronism (PA). Histology and long-term clinical follow-up normally serve as the gold standard for such diagnosis. We prospectively recruited 26 patients diagnosed with PA. All patients underwent 68Ga-Pentixafor PET/CT and AVS. Postsurgical biochemical and clinical outcomes of patients with unilateral primary aldosteronism (UPA), as diagnosed by PET/CT or AVS, were assessed by applying standardized Primary Aldosteronism Surgical Outcome (PASO) criteria. Immunohistochemistry (IHC) was performed to detect the expression of aldosterone synthase (CYP11B2) and CXCR4. On total, 19 patients were diagnosed with UPA; of these, 13 patients were lateralized by both PET/CT and AVS, four patients were lateralized by PET-only, and two by AVS-only. Seven subjects with no lateralization on AVS and PET received medical therapy. All patients achieved complete biochemical success except one with nodular hyperplasia lateralized by AVS alone. The consistency between PET/CT and AVS outcomes was 77% (20/26). Moreover, CYP11B2-positive nodules were all CXCR4-positive and showed positive findings on PET. Patients who achieved complete biochemical and clinical success had a higher uptake on PET as well as stronger expression levels of CXCR4 and CYP11B2. Our analysis showed that 68Ga-Pentixafor PET/CT could enable non-invasive diagnosis in most patients with PA and identify additional cases of unilateral and surgically curable PA which could not be classified by AVS. 68Ga-Pentixafor PET/CT should be considered as a first-line test for the future classification of PA.

Efficient Topical Treatment of Canine Nodular Sebaceous Hyperplasia with a Nitric Acid and Zinc Complex Solution.

Nodular sebaceous gland hyperplasia in the often middle-aged to old dog is a common, benign proliferation that results in exophytic, pink to yellow, alopecic, and often multilobulated nodules. Removal is usually carried out by surgical excision. As many old dogs have comorbidities that increase the risk of anesthesia, a topical treatment is warranted. We hypothesized that the application of a solution containing nitric acid, zinc, copper, and organic acids (Verrutop®), would be a safe and efficient way to treat these nodules. Eleven dogs with a total of 29 nodules, grossly compatible with nodular sebaceous gland hyperplasia, were included in the study. Eighteen of the nodules were treated; 11 were left untreated. No anesthesia or sedation was needed. Four weeks after one application, 17/18 treated nodules had decreased by 100% in volume. There was a statistically significant difference in percentual volume change between the treated and untreated nodules from day 0 to day 28 (p < 0.0001). No serious side effects were noted. Sebaceous hyperplasia cannot always be distinguished grossly from sebaceous tumors. Cytological evaluation can be helpful, and in cases of deviant macroscopic features, local recurrence, or more aggressive behavior, the appropriate intervention would be to biopsy or excise the nodule for histopathology. Topical application of Verrutop® is an easy, low-cost, and efficient way to remove canine sebaceous gland hyperplasia with minimal side effects in cases where surgery and anesthesia are not desired.

Histopathological features of idiopathic portal hypertension: A systematic review and meta-analysis.

Portal hypertension (PH) is a clinically significant entity that could present with life-threatening gastrointestinal bleeding. Cirrhosis is the most common cause of PH, with well-documented histopathology and etiology. However, in idiopathic portal hypertension (IPH), no single histopathologic finding is associated with PH. Our systematic review aims to identify and summarize the prevalence of the common histological findings of IPH. We systematically searched PubMed, Cochrane CENTRAL, Web of Science, and Scopus till 1ST March 2022 for studies describing the histopathological features of IPH. Data were extracted from eligible studies and pooled as events rate and 95% confidence interval (CI) using binary random-effects model by open meta-analyst software. We included 23 retrospective studies with a total sample size of 813 patients. The overall incidence of nodular regenerative hyperplasia was 38.6%, 59.8% for portal fibrosis, 51.3% for periportal fibrosis, 39.3% for perisinusoidal fibrosis, 89.8% for portal vein sclerosis, 42.2% for portal inflammation, 53.3% for mega-sinusoids, 39.5% for thickening of portal vein branches, 93.8% for narrowing of portal veins, 53.3% for hepatic veins/venous outflow obstruction, 51.4% for aberrant portal/periportal vessels, 42.4% for shunt vessel, 50.9% for ductular proliferation, and 16.3% for steatosis. Due to the relatively non-pathognomonic and non-specific nature of IPH, a combination of different histological features such as the portal and periportal fibrosis, portal vein sclerosis, mega-sinusoids, narrowing of portal veins, hepatic venous outflow obstruction, aberrant portal or periportal vessels, and ductular proliferation may be of value in diagnosing IPH as the incidence rate of these features was at approximately 50%.

A rare case of liver regenerative and non-neoplastic lesion resembling a well-differentiated hepatocellular carcinoma

BackgroundNodular regenerative hyperplasia (NRH) is a rare disease that presents pathologically as diffuse hepatic nodules without fibrous septa. It is believed to be caused by vasculopathy against a background of various systemic diseases, such as hematologic, autoimmune, and drug-induced diseases, with various symptoms. In spite of the recent imaging advances, various atypical cases of nodular lesions are observed in daily clinical practice. Cases that do not completely meet these criteria are referred to as -like or -similar lesions in clinical situations, making it difficult to understand their pathogenesis. We present a case in which two hepatic nodular lesions were noted and difficult to differentiate from malignancy preoperatively. The lesions were laparoscopically resected and a pathological diagnosis with non-neoplastic liver regenerative nodules resembling NRH was made.Case presentationA 49-year-old man with no alcohol or drug intake and no past medical history was identified as having liver tumors on screening examination without any symptoms. Contrast-enhanced computed tomography (CT) showed two hepatic tumors; approximately 2-cm tumors at S7 and S8. Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed fat inclusions in their contents. Ethoxybenzyl (EOB) uptake was also observed during the hepatobiliary phase. Based on preoperative examinations, we suspected well-differentiated hepatocellular carcinoma (HCC) and performed laparoscopic S7/8 partial resection for these lesions. Macroscopically, the resected specimens showed a non-cirrhotic yellowish-cut surface containing brownish, ill-defined lesions with irregular borders. Microscopically, these lesions showed zonal necrosis, congestion, and aggregation of hemosiderin-laden macrophages around the central vein. In these areas, the fatty deposition of hepatocytes was lower than that in the surrounding background hepatocytes. Histopathologically, neither neoplastic nor hyperplastic lesions were observed, and he was diagnosed as regenerative hepatic change with centrilobular necrosis.ConclusionsConsidering the pathological results, these lesions were thought to be a type of NRH-like lesion with possible hepatic vessel disorder. However, the lesion’s cause and classification was difficult to determine. The accumulation of these regenerative changes accompanying fatty liver is needed to clarify the mechanism and its clinical significance.

Pulmonary arterial hypertension associated with type II Abernethy malformation in an adolescent: a case report

The article provides a case of pulmonary arterial hypertension (PAH) associated with congenital extrahepatic portocaval shunt (CEPS), or Abernethy malformation, in a 17-year-old female patient. CEPS, which remained undiagnosed for a long time, manifested with severe encephalopathy at an early age. By the age of 6 years, it was complicated by PAH, and by the age of 9 years — by hepatic focal nodular hyperplasia. In the absence of timely surgical treatment and adequate therapy of CEPS, PAH progressed. Combined dual therapy for PAH, prescribed only at age 14, was ineffective. Despite the potential for clinical and functional improvement documented with combination triple therapy at 17 years of age, the patient continued to meet criteria for a high risk of adverse events, including mortality. Two months after the initiation of triple therapy for PAH, not achieving the target hemodynamic characteristics that would reduce operative and perioperative risks lead to an attempt of surgical treatment of CEPS, which led to the patient death in the early postoperative period. The description of this case report shows the difficulties of diagnosing a rare form of portopulmonary hypertension, the modern possibilities of drug therapy for a severe, potentially curable PAH in the early stages.

ACG Clinical Guideline: Focal Liver Lesions.

Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.

Incidental findings during donor liver assessment: Single center experience

Intraoperative consultation of donor liver is an important part of transplant evaluation and determination of liver eligibility. In this study, we describe incidental pathologic findings discovered during the pretransplant evaluation of liver donors in our Institution from 1/2010 to 12/2022. During this 13-year period 369 intraoperative consultations from 262 liver donors were performed. Of those cases, incidental findings were identified in 22 cases (5.9 %) from 19 donors (7.3 %); two donors had more than one lesion. The median age of this subset of patients was 53 years (range: 18–70) and females predominated (63 %). Sixteen of the donors had abnormal findings in the liver: 6 bile duct hamartoma (BDH), 5 hyalinized nodule with Histoplasma capsulatum, 5 focal nodular hyperplasia (FNH), 2 bile duct adenomas (BDA), 1 biliary cyst and 1 hemangioma. One donor had both FNH and a BDH. One BDH and 1 BDA case was misdiagnosed as malignancy during the frozen section evaluation. Three donors had extrahepatic pathologies: a pancreatic tail schwannoma, a low-grade appendiceal mucinous neoplasm, and a lymph node with metastatic endometrial endometrioid adenocarcinoma. Of the 19 livers, the final organ disposition was available for 9: 6 were transplanted (67 %) and 3 were discarded (33 %). Two of the 3 discarded organs were misdiagnosed BDH and BDA cases, and one was incorrectly reported as having 90 % microvesicular steatosis during the frozen assessment. We present the clinicopathologic characteristics of liver donors with incidental findings during the pre-transplant evaluation which could lead to unwarranted graft dismissal if misdiagnosed. Additionally, incidental fungal infections can have implications for immunosuppressive therapy and the decision to use or reject the graft.

Dissociation in hepatic vein pressure gradient, liver stiffness measurement and complications in histological subtypes of porto-sinusoidal vascular disease

Background and aimsPortosinusoidal vascular disease (PSVD) is a broad term encompassing varied histological patterns with changes in portal tracts and sinusoids without cirrhosis. We aimed to assess whether there is...

P-61 From Cushing to Nelson Syndrome: Diagnostic challenges and Surgical Dilemma

Abstract Introduction Diagnosis of the origin of ACTH-dependent Cushing's syndrome (CS) can be difficult in some cases, especially when MRI of the pituitary gland does not reveal an adenoma. Inferior petrosal (IPSS) or cavernous sinus sampling (CSS) with CRH stimulation helps confirm the central origin in most cases. CSS also helps lateralize the tumor within the pituitary gland with a sensitivity of 80%. Because transsphenoidal pituitary surgery is successful in the majority of MRI-negative cases, bilateral adrenalectomy is performed less frequently. Even with advanced radiologic studies, the origin may not be detected. Adrenalectomy may be an option in these cases. However, loss of feedback inhibition of the hypothalamic-pituitary-adrenal axis; can lead to aggressive transformation of an existing ACTH-secreting pituitary adenoma into Nelson's syndrome within 1-5 years. Clinical Case A 46-year-old female patient complaining of hot flashes and unable to lose weight was evaluated for CS and referred to the Department of Neurosurgery for a pituitary adenoma (Table 1). Since the adenoma was &amp;lt;6mm CSS with CRH stimulation was performed. The results did not support central origin (Table 2). Ectopic ACTH secretion was considered, but without finding the origin of the tumor on radiological examination, and treatment with ketoconazole and metyrapone was started for CS. However the patient then discontinued outpatient follow-up. The patient presented to our clinic 6 years later with a new pituitary MRI showing tumor growth (Fig.1b). She complained of fatigue and obesity. She was depressed and anxious. The skin on her face, hands and hump was dark and patchy (Fig.1c). During these years, she consulted several endocrinologists. MRI was performed annually. Brain MRI had showed a fronto-basal extraaxial mass lesion. The patient underwent microsurgical resection and pathology revealed a microcystic meningioma (WHO grade I). 3 months later bilateral nodular hyperplasia of adrenal gland was detected; she underwent bilateral laparoscopic adrenalectomy (no neoplasia). ACTH gradually increased up to 418pg/ml; the diagnosis of Nelson's syndrome was established. The patient underwent endoscopic transsphenoidal adenomectomy. The ACTH level was found to be 12pg/ml on the 2nd postoperative day. Pathological examination revealed a ACTH secreting pituitary adenoma (Ki-67:7%). CS patients suffer from emotional lability due to the effects of elevated cortisol and to the physical changes of their body. Proximal muscle weakness and obesity causes fatigue symptoms. The diagnosis is often delayed until complications occur. Differential diagnosis could be difficult and challenging. Patient's emotional lability could adversely affect treatment/follow-up compliance. The presented case had meningioma resection which could be delayed until remission from CD and bilateral adrenalectomy which could be avoided by endoscopic pituitary surgery. This case is a good example of the need for pituitary centers of excellence.Figure.Fig.1.a. MRI scan of the pituitary gland at first admission shows (a) a lesion extending posteriorly inferior to the right half of the pituitary gland, hyperintense at T2-weighted, iso-hypointense at T1-w, with heterogeneous contrast enhancement consistent with pituitary microadenoma (4mm*2mm) Fig.1.b. Progression in size of the adenoma (6mm*4mm) Fig.1.c. Darkening of the skin due to hypersecretion of ACTH. Table 1.Cavernous sinus sampling with corticotropin-releasing hormone stimulation Table 2.Laboratory tests in different times

To assess the quantitative features of focal liver lesions in gadoxetic acid enhanced MRI and to determine whether these features can accurately differentiate benign form malignant lesions

PurposeThe study aims at assessing the quantitative features which distinguish focal liver lesions (FLLs) in gadoxetic acid (GA) enhanced liver MRI and at determining whether these features can accurately differentiate benign from malignant lesions. Material and methods107 patients with 180 unequivocal FLLs in previous examinations were included in a single-center retrospective study. All patients underwent a MRI test of the liver with GA. 99 benign and 74 malignant lesions were included. The group of benign lesions consisted of 60 focal nodular hyperplasias (FNH), 22 hemangiomas (HMG), 6 hepatic adenomas (HA), and 11 other benign lesions (1 angiomyolipioma, 6 lesions histopathology diagnoses as benign without further specification, or ones lacking features of malignancy, and 4 lesions radiologically diagnosed as benign which remained stable in the follow-up studies). The group of malignant lesions consisted of primary 51 hepatocellular carcinomas, 12 metastases, and 11 metastases from melanoma malignum (MM meta). 7 FLLs were excluded (4 cases of uncertain histopathological diagnosis, 2 cholangiocarcinomas, and 1 regenerative nodule). For the included lesions ROI (region of interest) measurements were taken by two observers in the T2-w, ADC (apparent diffusion coefficient) and in the T1-w sequence in the hepatobiliary phase (HBP). The interobserver agreement was evaluated with the Wilcoxon test. The Kruskal – Wallis, Mann – Whitney U and post hoc Dunn’s tests were applied to assess if there were any significant differences in the ROI values between individual lesions.The variables with the p values of < 0.05 were considered statistically significant. ResultsWe found significant differences in the ROI values between lesions with p < 0.0001. Strikingly high ROI values in the T2-w sequence were found for HMG. The lowest ADC values were encountered for metastases and MM metastases. The highest ROI values in the HBP were found for FNH, and the lowest for metastases.We also found statistically significant differences in the ROI values between benign and malignant lesions with benign lesions presenting statistically higher ROI values compared to malignant lesions. ConclusionsThere were significant differences in the ROI values among different types of FLLs. The predominant quantitative feature in the T2-w sequence was a strikingly high ROI value for HMG. Benign lesions presented statistically higher ROI values in the T2-w, ADC, and HBP sequences compared to malignant lesions. This was true for all lesions except for HA.

Comorbidities in Angioedema Due to C1-Inhibitor Deficiency: An Italian Survey

BackgroundHereditary angioedema due to C1-inhibitor deficiency (HAE) is characterized by unpredictable recurrent episodes of swelling affecting the skin and the mucosa tissues, including gastrointestinal tract and/or oro-pharyngeal-laryngeal mucosae. Long-term prophylaxis (LTP) are used to prevent attacks. ObjectiveSince C1-inhibitor (C1-INH) plays a pivotal role in several biological pathways, we investigated the possible association of comorbidities with C1-INH deficiency and the use of LTP with androgens (AA) or tranexamic acid (TXA). MethodsThis retrospective cohort study involved adult patients with HAE referring to Milan and Padua angioedema centers in the period 1979-2021. A qualitative comparison was performed to analyze comorbidities vs. general population. The incidence of comorbidities was evaluated during LTP with AA or TXA vs. patients without LTP. ResultsA total of 446 patients were studied. A greater prevalence among patients was found for: heart diseases (9.6% vs. 4.8%), acute myocardial infarction (5.6% vs. 1.4%), HCV infection (10.5% vs. 2.5%), and appendectomy (15.9% vs. 4.3%). In patients taking AA a greater incidence was found for: hypertension (22.8% vs. 10.8%; OR 2.02), hypercholesterolemia (19.5% vs. 5.3%; OR 3.97), diabetes mellitus (5% vs. 1.4%; OR 3.21), hepatic angioma (4.4% vs. 0.7%; OR 8.35), and focal nodular hyperplasia (2.5% vs. 0.4%; OR 6.9). No association with TXA and comorbidities was found. ConclusionIn this large patient population with a rare disease followed for up to a 43-year period, we found a greater prevalence of comorbidities hitherto unreported in the literature and an association between comorbidities and LTP with AA.

Common variable immunodeficiency disorder-related liver disease is common and results in portal hypertension and an increased risk of death.

Common variable immunodeficiency disorder (CVID) manifests with recurrent infections and inflammatory complications, including liver disease. We report the clinical features, natural history, and outcomes of patients with CVID-related liver disease (CVID-rLD) from a tertiary immunology and hepatology center. Two hundred eighteen patients were identified; CVID-rLD was defined by persistently abnormal liver function tests or evidence of chronic liver disease (CLD) or portal hypertension (PHTN) by radiological or endoscopic investigation, after exclusion of other causes. Patients with CVID-rLD were investigated and managed following a joint pathway between immunology and hepatology services. Data, including clinical parameters, investigations, and outcomes, were retrospectively collected. A total of 91/218 (42%) patients had evidence of CVID-rLD, and 40/91 (44%) had PHTN. Patients with CVID-rLD were more likely to have other noninfectious complications of CVID (85/91, 93.4% vs. 75/127, 59.1%, p<0.001) including interstitial lung disease, gut disease, and autoimmune cytopenias. Nodular regenerative hyperplasia (NRH) was identified in 63.8% of liver biopsies, and fibrosis in 95.3%. Liver stiffness measurements (LSMs) were frequently elevated (median 9.95 kPa), and elevated LSM was associated with PHTN. All-cause mortality was higher in those with CVID-rLD (24/91, 26.4% vs. 14/127, 11%, p=0.003), which was the only organ complication associated with mortality (HR 2.24, 1.06-4.74, p=0.04). Factors predicting mortality in CVID-rLD included PHTN, increasing fibrosis, and LSM. Liver disease is a common complication of CVID as part of complex, multi-organ involvement and is associated with high rates of PHTN and an increased hazard of mortality.

A Case of Liver Cirrhosis with Inflammatory Autoimmune Liver Disease Associated with Portal Hypertension and Hepatic Haemangioma

Autoimmune Hepatitis (AIH) is a rare autoimmune disease that damages the liver over time and, if left untreated, can progress to liver cirrhosis. Clinical manifestations range from asymptomatic patients to those with acute hepatitis or chronic liver failure. Chronic autoimmune liver disease causes persistent liver injury, which results in unresolved inflammation, proliferation of cells, and the formation of extracellular matrix proteins by stellate cells of the liver and portal myofibroblasts. Cirrhosis of the liver and the resulting loss of normal liver function are unavoidable. Cirrhotic patients have a higher risk of morbidity and mortality, and problems of portal hypertension and/or liver dysfunction result in substantial deterioration in the decompensated phase. The theory suggests that among idiopathic or cryptogenic chronic hepatitis, most of them are autoimmune in origin. It is considered one of the rare liver diseases, especially in the Indian population. Portal hypertension is a dangerous complication caused by an obstruction in portal blood flow, such as cirrhosis or portal vein thrombosis. Hepatic Haemangiomas (HH) are benign liver tumours that are made up of groups of blood-filled cavities lined by endothelial cells and fed by the hepatic artery. The vast majority of HH are asymptomatic and are discovered by chance during imaging studies for unrelated pathologies. Hereby, the authors present a case of 53-year-old female with chronic liver disease with ascites, fatty change, and nodular hepatocellular hyperplasia, which was later found to be cirrhosis of autoimmune origin.

The Benevolent Wen-Hepatocellular Adenoma

Hepatocellular adenoma emerges as a benign, solitary neoplasm of hepatocellular origin preponderantly arising within non cirrhotic hepatic parenchyma. Lesion occurs secondary to obesity, metabolic syndrome and consumption of anabolic steroids or non-contraceptive oestrogen supplements. Concurrent to genetic mutations, hepatocellular adenoma is categorized as hepatocellular adenoma associated with HNF1A genetic mutation, hepatocellular adenoma associated with β catenin genetic mutation, inflammatory hepatocellular adenoma, sonic hedgehog (SHH) hepatocellular adenoma or hepatocellular adenoma, not otherwise specified. Cytological assessment exhibits bland, uniform hepatocytes permeated with regular nuclei and decimated nucleocytoplasmic ratio. Tumefaction may display a pseudo-acinar arrangement, foci of steatosis and attenuated, mildly thickened one to two cell thick cell plates with a well-defined perimeter and characteristic unpaired arterial configurations. Hepatocellular adenoma appears immune reactive to HepPar1 or reticulin and immune non-reactive to glypican 3, CD34 or HSP70. Neoplasm requires segregation from neoplasms such as focal nodular hyperplasia, well differentiated hepatocellular carcinoma, mass effect due to an adjacent mass lesion, haemangioma, lymphoma, echinococcal cyst, hepatoblastoma, and localized fatty change or metastatic lesions arising from various primaries, confined to hepatic parenchyma. Hepatocellular adenoma may be appropriately managed with surgical extermination.

Role of Alcian Blue Stain in Differentiating Prostatic Adenocarcinoma from Nodular Hyperplasia of Prostate

Objective: Enlargement of prostate is one of the leading cause of morbidity in men. Alcian Blue stain demonstrates that the acidic mucin is present in prostatic adenocarcinoma but absent in nodular hyperplasia of prostste. So this histochemical marker can be used in distinguishing them. This study aims to determine the role of Alcian Blue stain in differentiating prostatic adenocarcinoma from the nodular hyperplasia of prostate. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology, Rajshahi Medical College, Rajshahi and in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU) during the period of March 2018 to February 2020. Specimens were processed routinely for Haematoxilin and Eosin stain. The Alcian Blue stain was performed to demonstrate the presence of acidic mucin and the findings were categorized as positive or negative staining. Statistical analyses was carried out by using the Statistical package for Social Sciences (SPSS) version 20 for Windows. The components of accuracy test were computed by respective formulae for the tests. Result: The study involved a total 60 specimens of prostatic tissue among which 30 were histopathologically diagnosed cases of prostatic adenocarcinoma and another 30 were histopathologically diagnosed cases of nodular hyperplasia. Among the 30 cases of prostatic adenocarcinoma the acidic mucin was positive in 25 (83.3 %) cases and negative in 5 (16.7%) cases but in nodular hyperplasia it was positive in 8 (26.6%) cases and negative in 22 (73.4%) cases. The sensitivity of Alcian Blue stain in favour of malignancy was 83.3% and specificity was 73.3%. The overall diagnostic accuracy of Alcian Blue stain was 78.3% and it showed a statistically significant difference in staining between the cases of adenocarcinoma and nodular hyperplasia, indicated by p&lt;0.05. Conclusion: Alcian Blue stain has a valuable role in differentiating prostatic adenocarcinoma from the nodular hyperplasia. So it can be used in the diagnosis of prostatic adenocarcinoma. TAJ 2023; 36: No-2: 57-63

Focal hepatic hot spot sign: Clinical image

A 51‐year‐old women was hospitalized to start chemotherapy for small cell lung cancer diagnosed one months earlier. She underwent Computed Tomography (CT) of the chest and abdomen to re‐evaluate the progression of the lung tumour. Contrast-enhanced CT of the chest indicated an invasive anterior left lung tumour that caused an obstruction of the Superior Vena Cava (SVC) (Figure 1). Contrast-enhanced CT of the abdomen revealed an intense focal wedge-shaped homogeneous enhancement area in the quadrate lobe of the liver, which is known as the hot spot sign (Figure 2). Focal hepatic hot spot sign was first described by Ishikawa in 1983. The sign can be observed on technetium 99m (99mTc) Sulphur colloid scans or on contrast, material enhanced CT scans [1]. Hot spot sign is caused by portosystemic venous shunting between the superior vena cava and the left portal vein via the internal mammary and paraumbilical veins along the ligamentum teres, secondary to superior vena cava obstruction. The hot spot is created by areas of focally increased blood flow that result from this shunting [2]. Stanford and colleagues classified SVC syndrome into four types - type I and type II referred as supra-azygous partial and near complete obstruction of SVC with antegrade flow in azygous vein. Type III is defined as complete obstruction of SVC with reversal of azygous blood flow and type IV as complete obstruction of SVC and azygous system with development of chest wall collaterals [3]. This sign has been reported in Budd-Chiari syndrome, the causes of SVC syndrome (neoplasms of the thorax as lung carcinoma and lymphoma, Vasculo‐Behcet’s disease, fibrosing mediastinitis, and luetic aneurysm), and masses of the liver (abscess, haemangioma, focal nodular hyperplasia, and hepatocellular carcinoma) [4].

Patient with a novel syndrome with multiple benign hepatic lesions and extrahepatic neoplasms.

Simultaneous occurrence of benign hepatic lesions of different types is a sporadic phenomenon.To the best of our knowledge, we report the first clinical case of a syndrome with simultaneous manifestations of three different entities of benign liver tumors (hepatocellular adenoma, focal nodular hyperplasia and hemangioma) with a novel mutation detected in the liver adenoma and in the presence of a number of further extrahepatic organ neoplasms. Furthermore, we describe for the first time the presence of liver epithelial cells of hepatocytic phenotype expressing cytokeratin 7 (CK7) at the border of the adenoma.These findings may be important for explaining pathogenesis of benign as well as malignant tumors based on genetic and histopathological features.

Focal Nodular Hyperplasia: A Comprehensive Review with a Particular Focus on Pathogenesis and Complications.

Focal nodular hyperplasia is a benign tumor of the liver that is often found incidentally with imaging. The purpose of this review is to discuss the pathophysiology, rare complications that can occur due to these lesions, and management options. A literature review was performed on clinical trials and case reports involving focal nodular hyperplasia complications and management of these, as well as the proposed pathogenesis underlying these tumors. Although exposure to oral contraceptive pills and endogenous hormones have been thought to play a role in the development of these lesions, this has not been proven. Most recently, they are thought to arise as a consequence of a vascular anomaly causing alterations in the expression of angiopoietin genes. Complications are rare, but previous cases have reported associated pain, rupture and compression of nearby structures (hepatic vein, stomach, biliary system). Resection of focal nodular hyperplasia is not usually recommended. However, if there is associated pain with no other identifiable cause or presence of a large or growing lesion with risk of causing a complication, then surgical resection, radiofrequency ablation or arterial embolization should be considered.