Pitfalls in the histological diagnosis of total colonic aganglionosis on appendicectomy specimens

Background: Hirschsprung’s disease is the most important cause of functional intestinal obstruction in children. It is characterized by the absence of ganglion cells in the submucosal and myenteric plexuses on histology. In 10% of Hirschsprungs disease patients, involvement of the entire colon is seen in a condition called total colonic aganglionosis (TCA). The absence of ganglion cells in the appendix on histology has been considered diagnostic of TCA. The validity of this histological finding being taken as criteria for diagnosis is not clear. Aims and Objectives: This study examines the presence and the number of myenteric and submucosal ganglion cells in the appendices of suspected cases of TCA and compares these findings with controls, specimens of acute appendicitis, and histologically normal appendix in pediatric cases. Materials and Methods: Thirty-six appendix specimens of suspected TCA cases and controls, that is, ten each of acute appendicitis and histologically normal appendix in pediatric age group were included in this study taken up in the pathology department of a tertiary pediatric referral hospital. The presence or absence and the number of ganglion cells in each specimen was semiquantitatively evaluated in a blinded manner. These findings were descriptively compared and analyzed. The difficulties faced by the pathologist in reporting the pediatric appendix specimens were also documented. Results: The cases and controls showed that aganglionosis and no significant difference were noted in the number of ganglion cells per high power field between the cases and controls. The reporting pathologists enumerated quite a few pitfalls and problems encountered by them in the process of interpreting ganglion cell status of pediatric, particularly neonatal appendicectomy specimens. Conclusion: Aganglionosis of the appendix on histology may not be an ideal tool for the diagnosis of TCA. Difficulties in histological characterization of ganglion cells, technical errors in tissue embedding and the presence aganglionic skip areas might cause errors in the interpretation of ganglion cell status of appendix specimens, particularly infants, and neonates.

IgG4-Related Sclerosing Cholangitis: Rarely Diagnosed, but not a Rare Disease

IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.

Ganglioglioma Arising from the Septum Pellucidum

A 24-year-old gentleman presented to us with complaints of occasional headache for 2 years. Magnetic resonance imaging showed enhancing supra sellar mass with nonenhancing cystic components, extending superiorly up to the body of bilateral lateral ventricle, laterally displacing septum pellucidum, and compressing the third ventricle with obstructive hydrocephalus. Hormone profile depicted adrenocorticotropic hormone <5.00 pg/mL, growth hormone 1.32 ng/mL, insulin-like growth factor-1 <3.0 ng/mL. The patient underwent surgical resection. Histological finding was suggestive of ganglioglioma World Health Organization grade I. Customized immunohistochemistry panel was advised and revealed positive CD 56, NSE, and GFAP immunohistochemical stains. Gangliogliomas are less frequent neoplastic lesions confined to only a handful of case reports and studies. Accounting less than 2% of intracranial neoplasms, these lesions primarily affect those in the first 3 decades of their life. As ubiquitous it is in nature, we hereby present a case of ganglioglioma in a young adult male arising from septum pellucidum.

1594 Invasive Ductal Carcinoma with Osteoclast Giant Cells During Pregnancy: A Case Report and A Review of Literature

Mammary carcinoma with Osteoclast Giant Cells (OGCs) is a rare tumour. Although several cases were reported, the significance of this histological finding remains incompletely understood. OGCs may occur in several types of breast carcinoma with different epidemiological characteristics but, in association with pregnancy, OGCs has not been reported to date. Here we report a case 37-year-old presenting with a symptomatic breast lump in pregnancy that has been confirmed clinically and radiologically. Microscopic examination of biopsies and surgical specimens showed OGCs accompanying invasive ductal carcinoma with no evidence of axillary metastasis. Immunohistochemical analysis revealed tumour cells to be positive for oestrogen, and progesterone receptors, with human epidermal growth factor negative status (ER6, PR8, HER2 negative). This is the first case of OGCs during pregnancy to be reported, to our best of knowledge, following a search of the literature published in English language.

A Case Report of Tongue Lymphoepithelial Carcinoma with a Histological Diagnostic Dilemma

Most head and neck lymphoepithelial carcinomas (LECs) arise in the nasopharynx and harbor Epstein–Barr virus (EBV). LEC is also a rare subtype of the oral squamous cell carcinoma (SCC). Morphologically, LEC is defined as resembling non-keratinizing nasopharyngeal carcinoma, undifferentiated subtype. The histological features and pathogenesis of oral LEC are not established. We describe a case of tongue LEC with histopathological diagnostic difficulties. A 72-year-old Japanese female presented with a whitish change on her left-side tongue. The diagnosis was atypical epithelium; neoplastic change could not be ruled out by a biopsy. Although the lesion was monitored at our hospital per her request, invasive carcinoma was detected 11 months later. Microscopically, conventional SCC was observed with the characteristic features as LEC confined to the deep part of the lesion. We briefly discuss this unusual histological finding and make a novel proposal for distinguishing oral LEC from LECs in other regions based on these histological findings.

Squamous Metaplasia in a Borderline Phyllodes Tumor—an Undocumented Histological Finding in Male Breast: Report of a Case and Review of Literature

Phyllodes tumor is a paradigm of fibroepithelial neoplasm that accounts for <1% of the breast neoplastic lesions usually detected in females and uncommonly in the male breast. The World Health Organization classifies the tumor into benign, borderline, and malignant based on the predefined morphological criteria. Squamous differentiation in phyllodes tumor is epithelial metaplasia, which has been occasionally documented in English literature. We report the first undocumented case of a recurrent borderline phyllodes tumor with cystic squamous metaplastic change in a 32-year-old male patient. The histology was that of a fibroepithelial neoplasm with the typical leaf-like projections and cystic spaces lined by squamous epithelium containing keratin debris. The purpose of presenting this case is to elucidate the pathogenesis and discuss other malignant and benign breast lesions that may be included in the differential diagnosis when evaluating a breast lesion with squamous metaplasia, particularly in the context of fine-needle aspirates.

A RARE HISTOLOGICAL FINDING AFTER PANCREATICODUODENECTOMY

In this paper, we describe the case of successful surgical treatment of a rare combination of three malignant tumors of the major duodenal papilla in one patient. A 59-year-old woman presented with abdominal pain, fever, nausea, vomiting, weight loss and obstructive jaundice. After routine examination, the patient with suspected cancer of the major duodenal papilla underwent pylorus-sparing pancreatoduodenal resection. Final histology revealed a rare collision of three types of cancer in the major duodenal papilla invading the pancreatic head: moderately-differentiated adenocarcinoma (30 %), moderately differentiated squamous cell carcinoma (20 %) and poorly differentiated small cell neuroendocrine cancer (50 %), surgical resection margins were intact. Immunohistochemical analysis revealed positivity for synaptophysin, chromogranin A and cytokeratin 5/6. The tumor diameter of 2 cm and the absence of signs of locoregional spread allowed the process to be staged as T2N0M0, so the patient did not receive any adjuvant treatment. Follow-up CT performed 6 months later showed two lesions in the liver, and biopsy of one of them was performed. Metastasis of neuroendocrine cancer was histologically and immunohistochemically verified. She started first-line chemotherapy with etoposide + cisplatin.

MO400HISTOPATHOLOGICAL SPECTRUM OF SNAKE- BITE INDUCED KIDNEY INJURY IN INDIA: A SYSTEMATIC REVIEW

Background and Aims Snakebite is a public health problem leading to about 55,000 deaths every year in India. Kidney injury subsequent to snakebite envenomation is common ( reported prevalence up to 32%). It is estimated that 3% of total acute kidney injury (AKI) is attributable to snakebites. The current study aims to elucidate the spectrum of renal histopathology in AKI cases followed by snake bite. Method We searched seven electronic database studies to identify studies describing the histopathological findings in the kidney associated with snakebite envenomation from India. Two reviewers independently conducted titles and abstract screening as well as full-text evaluation for final inclusion decision. Data were extracted as per a standardized form and conducted narrative synthesis. Results We retrieved 1364 studies and finally included 21 studies involving 961 patients who met the eligibility criteria. Provisional results are presented. Patient ages ranged from 2.5 years to 80 years. Viper bite was the commonest cause related to AKI. 92 % of the AKI were oliguric and required dialysis. kidney biopsy was usually done after 3 weeks of AKI onset. Acute tubular necrosis (ATN) was the most common finding followed by acute interstitial nephritis, acute cortical necrosis, and thrombotic microangiopathy (TMA).Vasculitic changes in vessels were rarely reported. Conclusion Oligo-anuric presentation and prolonged kidney dysfunction were frequent in post snake bite AKI. ATN was the common histological finding

Severe Disease Activity and Liver Fibrosis Are Associated With a Lack of Hepatic Mitochondrial Adaptation in Patients With NASH

Dysfunctional mitochondrial function is believed to play a vital role in the progression of nonalcoholic steatohepatitis (NASH) to advanced fibrosis and cirrhosis. However, most evidence arises from animal models while there is limited data in humans. The characteristic histological finding of NASH is hepatocellular injury with ballooning and inflammation, often associated with fibrosis in advanced disease. The aim of this study was to assess the role of mitochondrial function (eg, oxidative phosphorylation [OXPHOS] in patients with vs. without NASH and fibrosis. To this end, we recruited 38 patients with NAFLD with risk factors (obesity and/or type 2 diabetes) for NASH (age: 52±12 years; 37% male; BMI: 39.6±8.5 kg/m2; HbA1c: 6.8±1.4%) in whom we assessed mitochondrial respiration and also performed measurements of insulin resistance (IR). Tissue was obtained by either a Tru-cut percutaneous liver biopsy (n=26) or a wedge biopsy during bariatric surgery (n=12). After tissue was separated for histological diagnosis, small liver samples (2–4 mg) were processed to quantify OXPHOS by measuring the mitochondrial oxygen consumption rate in individual complexes of mitochondria, expressed as pmol×mg wet weight-1×s-1, using high-resolution respirometry, Oxygraph-2k. Based on liver histology, patients with NASH (n=18) compared to without NASH (n=20), had worse hyperinsulinemia and HOMA-IR (25.2±10.5 vs 14.9± 6.7 µU/ml and 8.9±4.3 vs. 4.9±2.9 mg/dl × µU/ml, respectively) and higher OXPHOS (all p&lt;0.05), although well matched for age, BMI, HbA1c and % with diabetes. This was likely an adaptation to IR and higher FFA flux to the liver. We then examined patients based specifically on disease activity, using a combined score of hepatocyte ballooning and inflammation (necroinflammation score [NIS]) and divided as mild (n=16), moderate (n=14) or severe (n=8) NIS (also well matched for relevant clinical parameters). Patients in the moderate vs. mild NIS group disease activity had increased mitochondrial respiration as represented by OXPHOS (45.9±11.8 vs. 31.3±9.8), electron transport chain activity (ETC) (61.0±17.6 vs. 46.4±15.2) and state 3 respiration induced by ADP (20.7±4.9 vs. 16.4±4.6 pmol×mg wet weight-1×s-1; all p&lt;0.05). There was a trend for these parameters to decline in patients with severe vs. moderate disease activity, that was further accentuated when patients with NASH also had clinically significant fibrosis compared to those with mild or no fibrosis (OXPHOS: 37.9±7.8 vs. 49.8±12.5, p=0.04; and ETC: 49.8±13.4 vs. 67.5±16.1, p=0.02). Conclusion: In patients with NASH, there is an early hepatic mitochondrial adaptation to account for the state of more severe insulin resistance in steatohepatitis compared to simple steatosis. This adaptation is impaired when disease activity worsens and is most evident once patients develop steatohepatitis with significant fibrosis.

Atypical presentation of immunoglobulin G4-related disease as subglottic stenosis: a case-based review

Background Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory pathology that has been reported to affect principally the retroperitoneum, hepatobiliary system, salivary glands, orbital structures or lymph nodes. However, IgG4-RD with laryngeal involvement is a very rare entity. Our aims were to describe a case of subglottic stenosis as first and only manifestation of IgG4-RD and review the literature. A patient with IgG4-RD affecting the larynx that presented as subglottic stenosis is described. A MEDLINE database search of IgG4-RD cases with laryngopharyngeal manifestations was also conducted. A 30-year-old Caucasian woman was referred to a tertiary care hospital for dyspnea on exertion, which had been increasing for the last 4 months. Medical and surgical procedures revealed a subglottic stenosis, with a histological finding of IgG4 positive plasma cell infiltration. There was no evidence of other organ involvement. She was successfully treated with oral glucocorticoids and rituximab infusions. Glucocorticoids were rapidly tapered and the rituximab regimen was optimized, with no evidence of relapses. In the literature review, we found a total of 12 reported cases with laryngopharyngeal involvement, two of them with subglottic stenosis. IgG4-RD of the larynx is rare but should be considered after excluding more common disorders.