Calretinin Staining Research Articles

Calretinin Staining Pattern is Variable in Hirschsprung Disease Occurring in Patients with Down Syndrome

Abstract Introduction/Objective Hirschsprung disease (HD), a congenital absence of enteric ganglion cells, affects 2-10% of patients with Down syndrome (DS). Submucosal nerve hypertrophy (SNH) and abnormal calretinin immunohistochemistry (IHC) support a diagnosis of HD, but the concordance of these findings can be variable in DS. Recognizing differences in HD occuring in DS can provide insight into the disease and help to improve outcomes and reduce delays in diagnosis for these patients. We sought to describe the histologic and calretinin staining patterns in HD occurring in patients with DS. Methods/Case Report From 2017-2023, 22 rectal biopsies from 20 patients with DS were retrospectively collected and reviewed. Subsequent pull-through (PT) resections were evaluated from 8 patients. Biopsies were evaluated for ganglion cells and SNH. Calretinin IHC was qualitatively evaluated for intensity (strong, weak) and density (many, partial, rare). Quantitative analysis used a calculation of the percent area above threshold (%AAT) function of the NIH ImageJ software version 2.1.0. Representative areas of the PT resections were also evaluated by ImageJ %AAT analysis. Results (if a Case Study enter NA) HD biopsies (12/22, 54.5%) were from male patients (age 3 days-6 weeks) and showed SNH in 11/12 (91.7%) with a mean nerve diameter of 57.3 microns (range 25-89 microns). Ganglionated biopsies (10/22, 45.5%) were collected from patients 3 days to 12 years old (M:F ratio 1:1.5) and showed SNH in 6/10 (60%) with a mean nerve diameter of 44.4 microns (range 10-70 microns). Strong normal calretinin staining was only seen in ganglionated biopsies (7/10 non-HD versus 0/12 HD). Negative calretinin staining was only seen in HD (0/10 non-HD vs 7/12 HD). Abnormal staining was seen in both non-HD (3/10, 30%) and HD (5/12, 41.7%) as partial strong positivity and rare weak positivity, respectively. ImageJ %AAT quantitative analysis revealed an average of 1.71 in biopsies with strong calretinin expression, 0.130 with weak staining, and 0.033 with negative staining. Evaluation of 8 PT resections (mean length of aganglionosis 7.1 cm) showed a mean nerve diameter in the aganglionic segment of 88.3 microns, 49.6 microns in the TZ, and 32.7 microns in the ganglionated segment. ImageJ %AAT quantitative analysis of calretinin revealed a mean of 0.044 in the aganglionic area, 0.66 in the TZ, and 1.56 in the ganglionated segment. Conclusion Recognition of the variable calretinin patterns seen in rectal biopsies from patients with DS can assist in accurate and timely diagnosis of HD.

Immunohistochemical evaluation of CD34, CD117, and calretinin for diagnosis of hirschsprung’s disease

IntroductionHirschsprung’s disease (HD) is a neurogenic intestinal disorder attributed to incomplete neural crest cell migration during fetal intestinal development, leading to an aganglionic segment of the colon and functional obstruction. Associated malformations like intestinal atresia, hydronephrosis, and imperforate anus can accompany Hirschsprung’s disease. this study aims to evaluate the efficacy of Calretinin and Cajal cells (CD34 and CD117) immunohistochemical staining in improving HD diagnosis.MethodsThe study involved 70 pediatric patients suspected of Hirschsprung’s disease. Clinical, histopathological, and immunohistochemical analyses were conducted, focusing on calretinin, CD34, and CD117 markers to identify ganglion cells and Cajal cells. Data were statistically analyzed using SPSS software.ResultsIn the examination of the samples, the calretinin marker exhibited a consistent accuracy of 100% in diagnosing Hirschsprung’s disease (with sensitivity and specificity both at 100%). Regarding the markers for Cajal cells in cases of Hirschsprung’s disease, an irregularity in the arrangement of Cajal cells was observed, which was absent in normal cases. These markers also demonstrated a specificity and sensitivity of 100% in diagnosing the disease.ConclusionHirschsprung’s disease remains a complex condition with multifaceted pathophysiological mechanisms. Calretinin immunohistochemical staining offers enhanced diagnostic accuracy, while the debate surrounding ICC distribution underscores the need for advanced diagnostic techniques. Further research is warranted to unravel the intricacies of Hirschsprung’s disease and its associated complications.

Malignant Para-Testicular Mesothelioma: A Rare Presentation in the Tunica Vaginalis of an Elderly Male With No Prior Asbestos Exposure.

Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity.

Bilateral Gonadoblastoma in a 13-Year-Old Female with Turner Syndrome and Y Chromosome: A Case Report

Abstract Introduction/Objective Gonadoblastoma is a relatively rare type of ovarian tumor that has a high risk for patients with 45X/46XY. It is derived from the Y chromosome at its long arm GBY region, which contains the most likely candidate gene called testis-specific protein Y-encoded (TSPY). Methods/Case Report In this case report, we present a case of a 13-year-old girl with Turner syndrome whose cytogenetic test showed 45X with monosomy X and a siodicentric Yq chromosome. As she carried a high risk for the development of gonadoblastoma due to the presence of the Y chromosome and clinically had premature ovarian failure, she received further imaging studies, which did not reveal obvious ovarian masses. She underwent resections of bilateral fallopian tubes and ovaries. Bilateral fallopian tubes were unremarkable. However, within the bilateral ovarian tissue, foci of gonadoblastoma were found (0.5 to 0.6 cm), composed of large round germ cells (confirmed by positive OCT 3/4 and SALL4 stains) intermingled with oval-shaped sex cord-stromal cells forming tubular/cribriform structures (confirmed by positive staining for inhibin, calretinin, and FOXL2). The stromal cells of gonadoblastoma, but not germ cells, were positive for androgen receptor staining, while both components were negative for estrogen receptor staining. No invasive germ cell tumor or sex cord tumor was present. Results (if a Case Study enter NA) N/A Conclusion The positive androgen receptor staining in stromal cells of the gonadoblastoma supports the view that the Y chromosome-driven androgen system may play a role in the development of gonadoblastoma in a bi-cellular pattern.

Sclerosing Perivascular epithelioid cell neoplasms (PEComa), a rare variant in a unique family of tumors

Abstract Introduction/Objective Perivascular epithelioid cell neoplasms (PEComas) are a rare group of neoplasms that characteristically show both smooth muscle and melanocytic differentiation. The most common tumor in this family is renal angiomyolipoma but may occur in various sites. Sclerosing PEComa (S-PEComa) is an extremely rare variant. its only reported in females and it is usually an incidental finding in the retroperitoneum, in close proximity to the kidney. Methods/Case Report . We present a 52-year-old female, who had a chest CT scan for worsening cough. An - 4 cm exophytic renal mass in the left renal upper pole was found. Patient underwent left partial nephrectomy. Grossly the specimen consisted of 2.5 cm well-circumscribed, white tan mass, abutting the renal capsule, and extending into perinephric adipose tissue. Histology revealed uniform bland epithelioid cells with palely eosinophilic cytoplasm and round nuclei embedded in abundant densely sclerotic stroma. No fat was identified. Immunohistochemistry showed the tumor to be positive for desmin, HMB-45 and SMA with focal staining for AE1/AE3 and negative staining for EMA, cam 5.2, CD 117, calretinin, CD 34, S-100, PAX 8, and Melan A, which confirming the diagnosis of S-PEComa. Results (if a Case Study enter NA) NA Conclusion PEComas, excluding the epithelioid variant, usually has a benign course. In the 13 cases previously reported S-PEComa, 2 patients had metastasis. Our patient, 3-month post-op, has no evidence of disease, but close follow up still warranted.

BDNF Influence on Adult Terminal Axon Sprouting after Partial Deafferentation

BDNF is a neurotrophin family member implicated in many different neuronal functions, from neuronal survival during development to synaptic plasticity associated with processes of learning and memory. Its presence in the oculomotor system has previously been demonstrated, as it regulates afferent composition of extraocular motoneurons and their firing pattern. Moreover, BDNF expression increases after extraocular motoneuron partial deafferentation, in parallel with terminal axon sprouting from the remaining axons. To elucidate whether BDNF could play an active role in this process, we performed partial deafferentation of the medial rectus motoneurons through transection of one of the two main afferents, that is, the ascending tract of Deiters, and injected BDNF into the motoneuron target muscle, the medial rectus. Furthermore, to check whether BDNF could stimulate axon sprouting without lesions, we performed the same experiment without any lesions. Axon terminal sprouting was assessed by calretinin immunostaining, which specifically labels the remaining afferent system on medial rectus motoneurons, the abducens internuclear neurons. The results presented herein show that exogenous BDNF stimulated terminal axon growth, allowing the total recovery of synaptic coverage around the motoneuron somata. Moreover, calretinin staining in the neuropil exceeded that present in the control situation. Thus, BDNF could also stimulate axonal sprouting in the neuropil of intact animals. These results point to an active role of BDNF in plastic adaptations that take place after partial deafferentation.

DIFFUSE ECTOPIC DECIDUOSIS MIMICKING AS PERITONEAL CARCINOMATOSIS: A CASE REPORT OF A YOUNG FEMALE WITH MULTIPLE SEROSAL AND OMENTAL NODULES FOUND DURING A CAESARIAN SECTION

Background & Objectives: Ectopic deciduosis refers to an abnormal occurrence of decidual tissue beyond the endometrium, predominantly on the surface of the uterus, fallopian tubes, ovaries and omentum. Diffuse omental and perito-neal involvement is a perplexing manifestation that may mimic peritoneal carcinomatosis. It is not accompanied by any symptoms and complications in most of the cases and does not require treatment. However, rarely it can present with acute abdomen or imitate peritoneal malignancy and, thus, associated with diagnostic difficulties and unnecessary interventions. Aim of this case report is to describe a rare case of peritoneal deciduosis in a young female, found incidentally, during a caesarean section, mimicking metastatic nodules. Afutile hysterec-tomy along with omentectomy was performed.
 Methods: A case of diffuse ectopic deciduosis mimicking as peritoneal carcinomatosis in a 29 years young female with full term pregnancy was found during a lower segment caesarian section, undertaken in a tertiary care teaching hospital of Lahore, Pakistan. The histopathological diagnosis was based on common technique of paraffin embedding and hematoxylin-eosin staining along with ancillary immune-histochemical evaluation.
 Results: Histopathological evaluation showed ectopic decidual tissue consisted of solid nests and loosely cohesive aggregates; large polygonal cells with abundant granular eosinophilic cytoplasm; sharply defined cell borders, bland nuclei with dispersed chromatin and single conspicuous nucleoli on the surface of uterus and in omental fat. Weak staining for CD30 was observed in the decidual cell cytoplasm and negative staining for CK and Calretinin in decidual cells was found. Calretinin and CK highlight benign mesothelial cells and help to rule out differentials of mesothelioma and metastatic carcinoma.
 Conclusion: Peritoneal deciduosis represents a rare entity and it is important to consider this condition in patients, especially in pregnant women, to prevent unnecessary intervention In addition, distinguishing this condition from malignant neoplasms will help in deciding correct treatment options.

Combined histological and DNA methylome profiling approaches may provide insights into the pathophysiology of ovarian endometriomas.

To test the theory that invaginated ovarian surface epithelium and endometrial implants on the ovary form ovarian endometriomas. Adhesion sites of ovarian endometrioma on the peritoneum and consecutive ovarian endometrioma cyst wall, called non-adhesion sites, were histologically examined. DNA methylomes of the adhesion sites, non-adhesion sites, and blueberry spots were compared with those of ovary, endometrium, and peritoneum. The non-adhesion sites showed an ovarian surface epithelium-like structure near the adhesion site, which continued to a columnar epithelium-like structure. Calretinin staining was strong in the ovarian surface epithelium-like structure but weak in the columnar epithelium-like structure. Estrogen receptors were absent in the ovarian surface epithelium-like structure, but present in the columnar epithelium-like structure. The adhesion sites had endometrial gland-like structures that expressed estrogen receptors. Analyses of DNA methylomes classified the non-adhesion sites and ovaries into the same group, suggesting that ovarian endometriomas originate from the ovarian surface epithelium. The adhesion sites, blueberry spots and peritoneum were classified in the same group, suggesting that the adhesion sites and blueberry spots originate from the peritoneum. The present results support the invagination theory. Ovarian endometriomas consist of invaginated ovarian surface epithelium with celomic metaplasia and endometrium implants on the peritoneum.

Calretinin stain for the accurate diagnosis of atypical Cardiac Myxoma.

Calretinin stain for the accurate diagnosis of atypical Cardiac Myxoma.

RhoA and vigilin are candidates for immunohistochemical markers for epithelioid malignant mesothelioma

Diagnostic markers of malignant mesothelioma (MM) have been extensively investigated. Immunohistochemistry (IHC) markers, such as calretinin, have been used for pathologic diagnosis. However, more diagnostic markers are required to improve the specificity and sensitivity of pathologic diagnosis. This study proposed two proteins as diagnostic markers for epithelioid MM. One is RhoA, an MM mutation-susceptible locus-derived protein, and another is vigilin, a lung small cell carcinoma marker. IHC was performed using 93 MM (epithelioid, 71 cases; sarcomatoid, 13 cases; and biphasic, 9 cases), 64 lung adenocarcinoma (LAC), 60 lung squamous cell carcinoma (LSC), and 14 normal mesothelial (NM) tissues. The majority of epithelioid MM cases were positive for both RhoA and vigilin, whereas both IHCs showed lower stainability in biphasic and sarcomatoid MM. Besides, both IHCs showed significantly higher stainability for RhoA and vigilin in epithelioid MM than in LAC and LSC (p < 0.05). Chi-square tests showed that both RhoA and vigilin IHC positive rate in epithelioid MM was not significantly different from that of calretinin (p > 0.05). In the differential diagnosis of MM from lung cancer, the accuracy and specificity of RhoA, vigilin, and calretinin staining were almost equivalent. Further, H-score test showed that there was no significant difference between RhoA versus calretinin and vigilin versus calretinin in IHC positivity in epithelioid MM (p > 0.05). In conclusion, RhoA and vigilin may be candidates for immunohistochemical markers for epithelioid MM.

Calretinin Staining in Anorectal Line Biopsies Accurately Distinguished Hirschsprung Disease in a Retrospective Study.

The absence of submucosal ganglion cells does not reliably distinguish Hirschsprung disease from non Hirschsprung disease in anorectal line biopsies. Calretinin staining might be helpful in these biopsies. To determine its value, we analyzed calretinin positive mucosal neurites in anorectal line biopsies. Two pediatric pathologists, without access to patient data, evaluated calretinin positive mucosal neurites in anorectal line junctional mucosa in archival rectal biopsies contributed by 17 institutions. A separate investigator compiled patient information and sent data for statistical analysis. Biopsies with anorectal junctional mucosa from 115 patients were evaluated for calretinin positive mucosal neurites. 20/20 Hirschsprung disease biopsies were negative. 87/88 non Hirschsprung disease biopsies and 7/7 post pullthrough Hirschsprung disease neorectal biopsies were positive. Statistical analysis of the 108 non pullthrough biopsies yielded an accuracy of 99.1% (sensitivity 100%, specificity 98.9%). Age range was preterm to 16 years. Biopsy size was less than 1 mm to over 1 cm. Absence of calretinin positive mucosal neurites at the anorectal line was highly accurate in distinguishing Hirschsprung disease from non Hirschsprung disease cases in this blinded retrospective study. Calretinin staining is useful for interpreting biopsies from the physiologic hypoganglionic zone up to the anorectal line.

Inflammation and tissue remodeling contribute to fibrogenesis in stricturing Crohn's disease: image processing and analysis study.

BackgroundInflammation and structural remodeling may contribute to fibrogenesis in Crohn’s disease (CD). We quantified the immunoexpression of calretinin, CD34, and calprotectin as a surrogate for mucosal innervation, telocytes (interstitial cells playing a role in networking), and inflammation, respectively, and correlated them with bowel alterations in stricturing CD.MethodsPrimary resection specimens for ileal CD (n = 44, 31 stricturing CD, 13 inflammatory CD) were identified. Left-sided ulcerative colitis and trauma cases were used as controls. Proximal and distal margin and middle (diseased) sections were stained for calretinin, CD34, and calprotectin. Microscopic images were captured from the mucosa (calretinin), submucosa (calprotectin), and myenteric plexus (CD34), and the immunostaining was quantified using image processing and analysis. Bowel thickness at the corresponding sections were measured and correlated with the amount of immunoexpression.ResultsA total of 2,037 images were analyzed. In stricturing CD, submucosal alteration/thickening at the stricture site correlated with calprotectin staining and inversely correlated with calretinin staining at the proximal margin. Muscularis propria alteration/thickening at the stricture site correlated with mucosal calretinin staining at the proximal margin. Submucosal alteration/thickening at the proximal margin correlated with calretinin and CD34 staining at the proximal margin and inversely correlated with CD34 staining at the stricture site. Calretinin immunostaining at the distal margin was significantly higher in stricturing CD than the controls.ConclusionsInflammation and tissue remodeling appear to contribute to fibrogenesis in stricturing CD. Increased mucosal calretinin immunostaining distal to the diseased segment could be helpful in diagnosing CD in the right clinical context.

Diagnostic accuracy of calretinin and acetylcholinesterase staining of rectal suction biopsies in Hirschsprung disease examined by unexperienced pathologists

Rectal suction biopsy (RSB) is a gold standard for diagnosing Hirschsprung disease (HD). Calretinin staining of RSB is increasingly used by experienced pathologists due to non-complex examination and comparable diagnostic accuracy with acetylcholinesterase (AChE). However, the diagnostic accuracy of calretinin examined by unexperienced pathologists remains to be elucidated. Therefore, we aim to compare diagnostic accuracy of calretinin with AChE on RSB for diagnosing HD when examined by unexperienced pathologists. We prospectively analyzed sections from RSB stained with AChE + HE and calretinin. Blinded examination was done by five unexperienced pathologists (pathology residents) and three experienced pathologists (senior pediatric gastro-enterology pathologists) assessing for the presence of HD. Cases for the study included ones proven to be HD on resection specimens and cases without HD. Diagnostic accuracy was determined calculating area under the curve (AUC), sensitivity, specificity, likelihood ratio, and posttest probability. Fleiss’ kappa analysis was performed to assess interobserver agreement between reviewers. Eleven of 18 included patients (61%) were diagnosed with HD. Comparing the diagnostic accuracy of unexperienced pathologists, calretinin versus AChE + HE showed sensitivity of 80.0% versus 74.5% and specificity of 100% versus 65.4%, AUC of 0.87 (0.78–0.96) versus 0.59 (0.45–0.72). Unexperienced pathologists showed substantial agreement with calretinin (kappa 0.72 [0.61–0.84]) and fair agreement with AChE + HE (kappa 0.34 [0.23–0.44]). We found calretinin having higher diagnostic accuracy in diagnosing HD compared to AChE + HE when examined by unexperienced pathologists. Therefore, we recommend to use calretinin as the standard technique for staining RSB in diagnosing HD.

PERIPHERAL KERATOAMELOBLASTOMA/SOLID KERATOCYSTIC ODONTOGENIC TUMOR

<h3>Introduction</h3> Keratoameloblastoma (KAB) is considered a rare variant of ameloblastoma (AMEL). Three histomorphologic types exist: a) simple (acanthomatous ameloblastoma), b) complex with features of both AMEL and keratocyst odontogenic tumor (KOT/OKC), and c) papilliferous revealing papillary keratin-containing extensions in cystic ameloblastomatous lumina. There are two opposing theories on the development of KAB; 1) the tumor arises de novo as an ameloblastoma with exuberant keratin production, and 2) ameloblastomatous transformation occurs in preexisting KOT/OKC. Rare reports exist of solid KOT/OKC (SKOT) sharing features with KAB suggesting a hybrid lesion. Recently, it has been suggested that KAB should be reclassified as SKOT based on the presence of <i>ptch1</i>variants. Herein, we present a peripheral odontogenic tumor with features of KAB and SKOT. <h3>Materials and Methods</h3> 54-year-old male presented with a firm tender swelling of the right side of maxilla in the area of the premolars causing saucerization of the alveolar bone. <h3>Results</h3> Originating from surface epithelium, the tumor exhibited plexiform, follicular and cystic growth patterns with features encountered in KOT/OKC and stellate reticulum areas and reverse polarization in the periphery. Foci of mild pleomorphism and a few scattered mitoses were noted. Plexiform and cystic areas featured abundant keratin. Elongated lingulae infiltrating the connective tissue as well as plexiform extensions with predominantly ameloblastomatous features and few areas of keratinization were appreciated on the surface epithelium. The stroma revealed plasmacytic inflammation and multiple calcifications representing calcifying keratin deriving from burst cysts. Cytokeratin 19 plasmalemmal staining was observed. Keratin in calcifications was also stained. Ber-EP4 revealed focal plasmalemmal reaction in the surface epithelium with ameloblastomatous changes. There was no staining for calretinin and BRAF V600E. Variable Ki67 nuclear staining was noted. <h3>Conclusions</h3> Features of KAB and SKOT were observed. Next generation sequencing for the presence of <i>braf</i> or <i>ptch1</i> variants is underway.

S1752 Medullary Carcinoma of the Colon Presenting as Sepsis in a Patient With Ulcerative Colitis and Primary Sclerosing Cholangitis

Introduction: Medullary carcinoma (MC) of the colon is a rare histological subtype of poorly differentiated adenocarcinoma representing approximately 5-8 cases of every 10,000 colon cancers diagnosed. The prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis (PSC) ranges upwards of 50%, and the combination of both ulcerative colitis (UC) and PSC leads to a fourfold increase of colorectal cancer. Here we present a case of medullary colon cancer presenting as bilateral deep vein thrombosis (DVT) and sepsis, and to date there have been no reports of primary colonic MC in a patient with PSC. Case Description/Methods: A 30-year-old African American man with a history of UC on mesalamine and PSC on ursodiol presented with anemia and hematochezia. It was thought that he was having an UC flare and was treated with steroids. Colonoscopy showed multiple anal and rectal ulcers. Shortly after, he was diagnosed with bilateral lower extremity DVT, requiring placement of an IVC filter. He then developed sepsis, at which point he was diagnosed with E. coli bacteremia. CT scan showed a right lower quadrant necrotic and exophytic mass with surrounding adenopathy concerning for malignancy (Figure 1). Laboratory results demonstrated leukocytosis of 25.5, microcytic anemia with hemoglobin 7.6 g/dl and MCV 67.2 fl, thrombocytosis of 513 x 103/µL, elevated alkaline phosphatase of 574 U/L with total bilirubin of 1.9 mg/dL of which direct bilirubin was 1.3 mg/dL. SGOT 39 U/L, SGPT 58 U/L, GGTP 360 U/L. Carcinoembryonic Antigen (CEA) was elevated to 3.3 ng/mL. Colonoscopy demonstrated a large friable mass located in the ascending colon that appeared malignant and spanned approximately 4 cm (Figure 2). After undergoing a right hemicolectomy, pathology demonstrated poorly differentiated colonic MC with invasion through the muscularis propria (T3), with metastatic carcinoma identified in 8 of 43 lymph nodes (N2b). Discussion: Colonic MC tumors tend to be located proximally, rarely present with metastasis, and have been strongly associated with hereditary nonpolyposis colorectal cancer. It is twice more common in females and the mean age at diagnosis is 69.3±12.5 years. It is extremely rare in African Americans. These tumors can be difficult to distinguish from poorly differentiated adenocarcinomas and neuroendocrine tumors, but presence of positive calretinin staining in MC confirms diagnosis. This is the first report of MC of the colon in an individual with PSC, and one of the few in patients with UC.Figure 1.: A. CT abdomen/pelvis without contrast demonstrating a diffusely dilated, air-filled gastrointestinal tract extending from the stomach through the rectosigmoid colon. No transition point or obstruction noted. B. CT abdomen/pelvis with rectal contrast demonstrating an interposition of the hepatic flexure of the colon posterior and medial to the right lobe of the liver. No evidence of obstruction or strangulation noted. C. Endoscopy demonstrating a twisted, almost volvulus-like appearance at the splenic flexure, though without clear transition points.

SMARCA4-Deficient Undifferentiated Tumor Diagnosed on Adrenal Sampling.

SMARCA4-deficient undifferentiated tumor has distinct clinicopathologic features. We describe our experience with primary diagnosis on adrenal sampling. We collected six SMARCA4-deficient undifferentiated tumors diagnosed on adrenal sampling. Immunostains for SMARCA4, SF-1, inhibin, calretinin, S-100 protein, EMA, and TTF-1 were performed. A control group of 63 primary adrenocortical tumors was also immunostained. Patients included four men and two women (aged 52-77 years). Five had unilateral adrenal masses and one bilateral (range, 2.4-9.6 cm). Five had pulmonary masses, and one had a midline mediastinal mass. All cases had a monotonous epithelioid appearance and variable rhabdoid morphology. Immunophenotypically, all six cases had loss of nuclear SMARCA4 expression and no staining for SF-1, inhibin, calretinin, or S-100 protein. Variable EMA immunoreactivity was present in four of six cases and focal nuclear TTF-1 expression in one of six. All 63 adrenocortical neoplasms had retained nuclear SMARCA4 expression. SMARCA4-deficient undifferentiated tumor may present in the adrenal gland, and this series likely represents metastases from thoracic primaries. Because of the frequent absence of lineage marker expression, knowledge of the characteristic clinical presentation, the rhabdoid morphology, and the typical immunophenotype (loss of SMARCA4/BRG1) allow for appropriate distinction from adrenocortical carcinoma.

Autopsy Study of Calretinin Immunohistochemistry in the Anorectal Canal in Young Infants and Potential Implications for Rectal Biopsy Approach in the Neonatal Period.

Absent submucosal ganglion cells in biopsies 1-3 cm above the pectinate line establishes the pathologic diagnosis of Hirschsprung Disease (HD). Calretinin stains both ganglion cells and their mucosal neurites and has gained importance in HD diagnosis. Absent calretinin positive mucosal neurites in biopsies at the appropriate level above the pectinate line is highly specific for HD. Whether this applies to lower biopsies is uncertain. To address this, we studied anorectal canal autopsy specimens from infants. We performed an autopsy study of infant anorectal canal specimens to describe calretinin staining in this region. Calretinin staining was correlated with histologic and gross landmarks. In all 15 non-HD specimens, calretinin positive mucosal neurites were present in glandular mucosa up to the anorectal line where neurites rapidly diminished. Age range was preterm 26 weeks to 3 months. Calretinin positive mucosal neurites are present in glandular mucosa up to the anorectal line in young infants. This is potentially important regarding neonatal HD biopsy level and diagnosis. Positive calretinin staining at the anorectal line favors normal innervation making HD unlikely. Absent calretinin positive neurites in glandular mucosa is worrisome for HD in young infants, regardless of location.

MOC31 Immunostaining in the Diagnosis of Metastatic Adenocarcinoma in Serous Fluid: Special Emphasis on Atypical Cytological Cases

Background: The diagnosis of atypical cases in the effusion cytology sample often poses a challenge to the cytologists. Aims and Objectives: We evaluated the diagnostic role of MOC31 in the metastatic adenocarcinoma in effusion fluid. Materials and Methods: The cytological examination and MOC31 immunostaining in the cell block sections were carried out in 64 cases of serous effusion. A total of 23 cases showed atypical cytology, out of which suspicious for malignancy (SFM) and atypia of undetermined significance (AUS) were 19 and 4 cases, respectively. In these cases, we also performed calretinin immunostaining. The cytological features, results of MOC31 immunostaining, and follow-up data were correlated to find out the sensitivity and specificity of MOC31 immunostaining in the diagnosis of metastatic adenocarcinoma. Result: The sensitivity and specificity of MOC31 were 100%. MOC31 detected all the cases of metastatic adenocarcinoma. MOC31 showed strong positivity in 19 cases of SFM. All these cases had a malignant outcome in histopathology or follow-up data. In AUS cases, MOC31 immunostaining was negative with a benign outcome. In all the atypical but malignant cases calretinin stain showed diffuse cytoplasmic and nuclear positivity. In contrast, MOC31 showed strong membranous positivity and occasionally cytoplasmic positivity. Conclusion: MOC31 is an excellent marker of metastatic adenocarcinoma in the serous effusion. The membranous positivity of MOC31 and negative calretinin immuno­staining are helpful in atypical cytological cases to avoid the diagnostic dilemma. The MOC31 positivity is significantly useful in discrete atypical cells which are more challenging to recognize.

The significance of detecting glucose transporter 1 and calretinin in serous effusions to differentiate between carcinoma cells and reactive mesothelial cells.

The cytologic evaluation of serous effusions to distinguish malignant cells from reactive mesothelial cells (RMCs)was an enormous challenge. The purpose of this study was to investigate the diagnostic value of glucose transporter 1 (GLUT1) and calretinin (CR) in serous effusions of patients with malignant and in order to significantly ameliorate the diagnostic accuracy. The expressions of GLUT1 and CR were measured by streptavidin-peroxidase (S-P) immunocytochemical technique in serous effusions of 183 patients with malignant and in 95 patients with benign diseases. The positive ratio of GLUT1 was 91.8% (168/183) in serous effusions from patients with malignant and 5.3% (5/95) in benign diseases, they had a significant difference (P < .01). CR was expressed 89.5% (85/95) in benign diseases and 6.6% (12/183) in malignant, it also showed an important difference (P < 0.01). The combination of GLUT1 + CR revealed the best efficiency: the sensitivity and specificity were 100% and 98.9%, respectively. Immunocytochemical staining for GLUT1 and CR may be used as a complementary tool for the detection of malignant effusions and help to make a distinction between cancer cells and RMCs. The combination of GLUT1 and CR with immunocytochemistry stained can be achieved a higher diagnostic performance.

Diagnostic Role of Calretinin in Suspicious Cases of Hirschsprung's Disease.

BackgroundHirschsprung’s disease (HD) is a developmental disorder of the intrinsic component of the enteric nervous system. It is characterized by the absence of ganglion cells in the myenteric and submucosal plexus. Histopathological diagnosis becomes difficult many times due to submucosal ganglionic cells are not easily identifiable.Aims and objectiveThe aim of this study was to examine the clinical and histopathological features of HD and to establish the utility of calretinin staining to diagnose the case of suspicious HD.Materials and methodsAfter taking necessary informed consent, we studied 41 cases in which clinical suspicion of HD had been made, in a study duration of three years (July 2017-June 2020). Open biopsies were taken from spastic segment, transition zone and dilated segment. Histopathological diagnosis had been made in three categories: HD, no Hirschsprung's disease (NHD) and suspicion of HD. Post histopathological diagnosis calretinin immunohistochemistry (IHC) was applied to all cases and interpretations were noted.ResultsOn the basis of histopathological findings, 25 cases were diagnosed as HD, nine cases were marked for suspicion for HD and seven cases as NHD. After evaluating calretinin IHC on the suspicious case, total of 30 cases were confirmed as HD while the remaining 11 cases were confirmed as NHD. Twenty-four patients of HD were males while the remaining six cases were females. The age of patients ranged from four days to 10 years. Median age six days while 22 patients were in the neonatal period.ConclusionCalretinin immunostaining is a useful modality in diagnosing suspicious cases of HD. Its results are easy to interpret by less experienced pathologist with accuracy.