Patterns and Grading of Gastrointestinal Graft-Versus-Host Disease: A Clinicopathologic Correlation Study.

BACKGROUND: The present study investigated gastrointestinal involvement patterns of acute graft-versus-host disease and assessed the correlation of pathologic severity with clinical grading. METHODS: Pathology reports of gastrointestinal (GI) endoscopic biopsies taken from 164 post-hematopoietic stem cell transplant patients with at least 1 endoscopic gastrointestinal biopsy diagnosed as "consistent with acute graft-versus-host disease" between 2005 and 2019 were retrieved from the automated hospital database. Endoscopic, pathologic and clinical gradings were performed using Freiburg criteria, Lerner and modified Seattle-Glucksberg grading systems, respectively. RESULTS: The majority of the patients (n = 140, 85.4%) were investigated with more than one biopsy from various gastrointestinal sites with a total of 479 biopsies: 44 (9.2%) esophagus, 90 (18.8%) stomach, 91 (19.0%) duodenum, 20 (4.2%) terminal ileum, 32 (6.7%) right colon, 87 (18.2%) left colon and, 115 (23.9%) rectum. Overall, lower gastrointestinal (n = 118/126, 93.6%) and upper gastrointestinal (n = 91/97, 93.8%) involvements were similar (P = .3). While the most severely affected site was duodenum (P = .021) in upper gastrointestinal, pathologic grades were similar in lower gastrointestinal sites, though more severe than upper gastrointestinal (P = .003). Pathologic grading had a low positive correlation with both clinical (r = 0.308, P = .001) and endoscopic grading (coefficient: 0.261, P = .003). CONCLUSION: Considering the similar graft-versus-host disease frequency of upper and lower gastrointestinal tract, distal colon evaluation with rectosigmoidoscopy seems to be a practical approach in patients with suspected gastrointestinal graft-versus-host disease. As it was positively correlated with both endoscopic and clinical grade, pathologic grading should be performed in these patients to assess gastrointestinal involvement patterns.

Anterior segment optical coherence tomography in ocular surface tumours and simulating lesions.

This study aims to systematically review the reported literature on the use of anterior segment optical coherence tomography (AS-OCT) in ocular surface tumours and simulating lesions. A systematic literature search was done using PubMed, Scopus, and Web of Science databases between January 2002 and December 2021. On AS-OCT, ocular surface squamous neoplasia typically demonstrate epithelial thickening, epithelial hyperreflectivity, and an abrupt transition between normal and abnormal epithelium. Conjunctival nevi usually show mildly hyperreflective epithelium of normal thickness, internal hyperreflectivity, and intralesional cysts which is the hallmark of this tumour. Primary acquired melanosis presents with normal thickness epithelium, basal epithelial hyperreflectivity, and absence of cysts. Conjunctival melanoma demonstrates hyperreflective normal/thickened epithelium, hyperreflective basal epithelium, internal hyperreflectivity, and absence of intralesional cysts. Conjunctival lymphoma shows homogenous, low-medium reflective subepithelial lesions with smooth borders, and dot-like infiltrates. Benign reactive lymphoid hyperplasia findings are similar to lymphoma but the infiltrates are more hyperreflective compared to lymphoma. Pterygium shows thickened conjunctival epithelium, epithelial hyperreflectivity, and subepithelial wedge-shaped hyperreflective tissue separated from the overlying epithelium by a cleavage plane. Pinguecula demonstrates mildly thickened epithelium and similar findings with pterygium but does not extend beyond the corneal limbus. This review shows that AS-OCT, as a noninvasive tool, has potential uses in the differential diagnosis of ocular surface tumours and simulating lesions. Major limitations of AS-OCT include limited visualization of the posterior border of thick, keratinized, and pigmented tumours and lack of assessment of large conjunctival tumours in a single cut.

Endonasal endoscopic approach for sellar metastatic pathologies: a national observation.

PURPOSE: Sellar metastases are rare lesions. Recent improvements in diagnosis and treatment strategies have prolonged survival but increased the probability of metastatic tumors. Evaluation with clinical symptomatology and meticulous laboratory examination is crucial. We present our multicenter national study on sellar metastases to evaluate and underline the main clinical, endocrine, and radiological considerations regarding the diagnosis and endonasal endoscopic management of such rare lesions. METHODS: A medical literature-based retrospective study was planned across 13 neurosurgical centers in Turkey, where a data survey was conducted to collect information regarding sellar metastases surgically treated using the endoscopic endonasal approach, including clinical presentation, radiographic features, primary tumor origin, histopathological confirmation, time to metastasis, treatment, and patient outcomes. RESULTS: Between 2010 and 2020, 54 patients (22 women [40.7%] and 32 men [59.3%]) who underwent surgery with the endonasal endoscopic approach and had pathologically proven sellar metastases (overall incidence, 0.54%) were included. Of the patients, 59.3% had no known malignancy and presented with new-onset symptoms, 79.6% reported headache, 51.9% complained of some degree of visual deficits, and 50% had cranial nerve symptoms. Tissue biopsy was performed in 7.4% of the patients, whereas gross or subtotal resection was achieved in the remaining patients. CONCLUSION: To our knowledge, this is the largest series of patients surgically treated with the endonasal endoscopic approach for sellar metastases. For these patients, the treatment focus should be on management modalities for increasing quality of life instead radical treatment options with survival benefit.

Morphology of the trigeminal ganglion: anatomical structures related to trigeminal radiofrequency rhizotomy.

BACKGROUND: Trigeminal neuralgia is the most common example of craniofacial neuralgia. Its etiology is unknown and is characterized by severe episodes of paroxysmal pain. The trigeminal ganglion and its adjacent anatomical structures have a complex anatomy. The foramen ovale is of great importance during surgical procedures such as percutaneous trigeminal rhizotomy for trigeminal neuralgia. OBJECTIVE: We aimed to identify the anatomical structures associated with the trigeminal ganglion and radiofrequency rhizotomy on cadavers and investigate their relationship with the electrodes used during rhizotomy to determine the contribution of the electrode diameter and length to the effectiveness of the lesion formation on the ganglion. METHODS: Five fresh-frozen cadaver heads injected with red silicone/latex were used. A percutaneous puncture was made by inserting of a cannula through the foramen ovale to create a pathway for electrodes. The relationships between the electrodes, Meckel's cave, trigeminal ganglion, and neurovascular structures were observed and morphometric measurements were obtained using a digital caliper. RESULTS: Trigeminal ganglion, therefore the electrode in its final position, shows proximity with important anatomical structures. The electrode was inserted posteriorly into the foramen ovale in all of the specimens and was located on the retrogasserian fibers. This study revealed that the electrodes targeting the ganglion and passing through the foramen ovale may cause a radiofrequency lesion due to the contact effect of the dura itself pressing on the electrode. Pushing the cannula beyond the petroclival angle may result in puncturing of the dura propria and moving further away from the target area. CONCLUSION: The success of radiofrequency rhizotomy is directly related to the area affected by the lesion. Understanding the mechanism of action underlying this procedure will ensure the effectiveness, success, and sustainability of the treatment.

Systematized Epidermal Nevus Syndrome Involving the Upper and Lower Eyelids Bilaterally

A 29-year-old woman presented with dark-colored raised lesions on both eyelids since early childhood. Ophthalmological examination revealed pigmented verrucous lesions on her upper and lower eyelids bilaterally. The patient had a history of generalized tonic-clonic seizures. Dermatological examination revealed hyperpigmented verrucous plaques arranged along lines of Blaschko on the neck, trunk, and arms. On the basis of these findings, the diagnosis of epidermal nevus syndrome (ENS) was made. She had surgery for debulking of the lesions. Histological analysis revealed hyperkeratosis with foci of parakeratosis, acanthosis, and papillomatosis, consistent with linear verrucous epidermal nevus. Postoperative residual lesions did not respond to oral acitretin therapy (10 mg/kg/day for 2 months). Systematized ENS can rarely cause linear verrucous nevi on the upper and lower eyelids on both sides. These patients should be investigated for accompanying systemic anomalies and followed for potential malignant transformation of the skin lesions.

The role of unfolded protein response in the pathogenesis of endometriosis: contribution of peritoneal fluid.

RESEARCH QUESTION: Endoplasmic reticulum stress (ERS) is caused by the accumulation of the misfolded or unfolded proteins in the endoplasmic reticulum and induces the unfolded protein response (UPR). Peritoneal fluid is important in the pathogenesis of endometriosis. In this study, the role of UPR associated with ERS in endometriosis, and peritoneal fluid, were investigated. DESIGN: Normal, eutopic and ectopic endometrium tissues were divided into menstrual cycle phases, and endometrial stromal cells (ESC) were treated with 10-20% concentration of control peritoneal fluid and peritoneal fluid obtained from women with endometriosis for 10, 30 and 60 min, and 24 and 48 h. The UPR signalling proteins were analysed immunohistochemically and immunocytochemically. Data were compared statistically. RESULTS: p-IRE1 was increased in ectopic glandular and stromal cells in the early proliferative phase compared with normal and eutopic endometrium. p-PERK increased in ectopic glandular and stromal cells in the late proliferative phase compared with normal endometrium. ATF6 was increased in ectopic glandular epithelium compared with normal endometrium in the proliferative phases, versus eutopic endometrium in the late secretory phase. p-IRE1 and p-PERK were increased in high concentrations of ESC treated with peritoneal fluid obtained from women with endometriosis for 10, 30 and 60 min compared with controls. In ESC treated with peritoneal fluid from women with endometriosis, p-IRE1 decreased at 24-48 h compared with 30 min. CONCLUSIONS: In endometriosis, UPR pathways are activated as highly dependent on cell type and phase. Also, p-PERK and p-IRE1 increased because of exposure to high-dose peritoneal fluid from women with endometriosis in stromal cells. Our findings provide a basis for further studies searching for a potential biomarker for the diagnosis of endometriosis.

Adenoid cystic carcinoma of Bartholin's gland diagnosed after lung lobectomy: Review of the literature and a case presentation.

Bartholin's gland was first identified in human female in 1675 by Caspar Bartholin. The Bartholin gland is composed of several epithelial types: The body is mucinous acini, the duct is predominantly transitional epithelium, and the orifice is the squamous epithelium. Primary carcinoma of the bartholin's gland is an uncommon neoplasm. Adenoid cystic carcinoma (ACC) of bartholin gland carcinom is a rare variant of bartholin gland carcinoma, comprising 15% of all bartholin gland malignancies. ACC of the Bartholin's gland is characterized by slow growth so recurrence and distant metastases can take a long period. So distant metastasis has been found in only a few cases to the lungs, liver, bone and brain. Here, we present the case of Bartholin's gland ACC after four years follow up and presented with a lung metastasis.

Gastric and small intestinal traditional serrated adenomas: a detailed morphologic and immunohistochemical analysis.

BACKGROUND/AIMS: Traditional serrated adenomas (TSAs), despite their low incidence in colorectum, may originate in other parts of the gastrointestinal (GI) tract, including stomach and small intestine. Malignant transformation for upper GI TSAs has recently been reported in the literature. Here, we present a series of gastric and small intestinal TSAs with the aim to characterize their morphologic and immunophenotypic features as well as their neoplastic potential in a compartmental manner using digitalized images. MATERIALS AND METHODS: The study comprised 12 GI polyps with TSA features-5 gastric and 7 small intestinal. The extent of the characteristic features of TSA, including eosinophilic cells, ectopic crypt foci (ECF), slit-like serration, foveolar epithelium, goblet cells, together with dysplastic-carcinomatous foci were assessed on digitalized H-E images and were used as reference for immunohistochemical analysis. RESULTS: All polyps in the cohort contained eosinophilic cells as the most extensive morphologic feature followed by ECF and slit-like serration in decreasing order. Serrated dysplasia was more common in gastric polyps, which more frequently showed neoplastic progression compared with the intestinal ones. CK20 was the most widely expressed marker with a preference to eosinophilic cells while ECFs were mostly negative. Ki67 showed the opposite pattern of CK20. MUC6 and MUC2 were selectively expressed in the basal zone and goblet cells, respectively. CONCLUSION: Our results showed that the presence of eosinophilic cells with pencillate nuclei commonly accompanied by ECF and slit-like serration are the defining features of gastric and small intestinal TSAs. They frequently harbor neoplastic foci, particularly in gastric location where serrated dysplasia seems to be more common.

Anterior segment optical coherence tomography, in vivo confocal microscopy, histopathologic, and immunohistochemical findings in a patient with multiple endocrine neoplasia type 2b.

PURPOSE: To describe clinical, anterior segment optical coherence tomography (AS-OCT), in vivo confocal microscopy (IVCM), histopathologic, and immunohistochemical findings in a patient with multiple endocrine neoplasia type 2b (MEN 2b) syndrome. MATERIALS AND METHODS: Retrospective case report of a patient with MEN 2b. RESULTS: A 31-year-old male diagnosed with MEN 2b presented with eye redness, burning, and visible conjunctival mass in both eyes. The patient's past medical history revealed that he underwent bilateral adrenalectomy and total thyroidectomy. Genetic testing revealed M918T heterozygous mutation in the RET proto-oncogene. Corrected visual acuity was 20/20 in both eyes. Anterior segment examination revealed bilateral thickened lid margins, ectropion, blepharitis, conjunctival injection, temporal and inferonasal subconjunctival lesions with corneal invasion, corneal neovascularization, and marked corneal nerves. AS-OCT showed a subepithelial mixed reflective lobular mass in both eyes. Hyperreflective and noticeable thickened stromal corneal nerves were observed on IVCM in the left eye. After incisional biopsy of the right perilimbal lesions, histopathological examination revealed that lesions consisted of spindle cells in hypocellular bundles with no atypia and mitosis. Immunohistochemical examination revealed diffuse staining with S100, focal staining with synaptophysin, and no staining with neurofilament protein. These findings were considered compatible with a benign nerve sheath tumor, probably schwannoma. CONCLUSIONS: We present clinical, AS-OCT, IVCM, histopathological, and immunohistochemical findings in a patient with MEN 2b. To our knowledge, this is the first case of a conjunctival schwannoma diagnosed histopathologically in MEN 2b.

Is it possible to discriminate pulmonary carcinoids from hamartomas based on CT features?

PURPOSE: The purpose of this study was to determine whether the computed tomography (CT) features might be used in distinguishing pulmonary carcinoids from hamartomas. MATERIALS AND METHODS: Ninety solid pulmonary nodules (43 carcinoids and 47 hamartomas) in 90 patients were evaluated. The following CT scan features were evaluated: size, location (peripheral/central), contour (lobulated/nodular), number of lobulation, attenuation, calcification, endobronchial status, bronchial extension and involvement, parenchymal abnormalities distal to the lesion e.g. hyperlucency, atelectasis, and nodularity. The final pathologic diagnosis of the lesions and bronchial extension were confirmed by review of histopathological specimens. RESULTS: Out of 43 carcinoids, 37 (86%) were typical. Twenty-three carcinoids and four hamartomas were central (p < 0.001). Ten carcinoids and one hamartoma were endobronchial. The majority of tumors had lobulated contours (65% of carcinoids, 44% of hamartomas) and carcinoids tended to have more lobulations (p = 0.052). Distal nodularity (p = 0.001), distal hyperlucency (p < 0.001), and atelectasis (p = 0.005) were significantly more common in carcinoids. Carcinoids had significantly more bronchial extension and involvement (p < 0.001; respectively). In addition, a new sign that we call "bronchial triangle sign" differentiated carcinoids with a sensitivity and specificity of 84.9% (95% CI: 69,1%-93.4%) and 91% (95% CI: 79.7%-96.6%). CONCLUSION: To the best of our knowledge this is the first study on discrimination of carcinoids and hamartomas. A new CT sign called "bronchial triangle sign" might be used to differentiate carcinoids from hamartomas. Distal parenchymal abnormalities are more common in carcinoids than in hamartomas.

Primitive neuroectodermal tumor of genital tract in hysterectomized patient: A case report.

Primitive neuroectodermal tumors are high-grade malignant neoplasms. These are uncommon entities for the female genital tract. The treatment, management and follow-up period of Ewing's tumors are not well-defined because of their rarity in the genital tract. Surgical debulking is the mainstay treatment in all cases. After debulking surgery, patients receive chemotherapy and/or radiotherapy and there is a relation between disease stage and survival. Herein, we present a case of ovarian primitive neuroectodermal tumor with a review of previously reported cases.

Clinical Impact of p27Kip1 and CaSR Expression on Primary Hyperparathyroidism.

We aimed to investigate the expressions of p27 kinase inhibitory protein 1 (p27Kip1) and calcium sensing receptor (CaSR) in adenomas and normal parathyroid tissue and to evaluate the relationship of these molecules with clinical and biochemical parameters in primary hyperparathyroidism (PHPT). Fifty-one patients with histopathologically confirmed parathyroid adenomas and 20 patients with normal parathyroid glands (which were removed incidentally during thyroid resection) were included. Immunohistochemical stainings of CaSR and p27Kip1 were performed in surgical specimens. Clinical features, biochemical parameters, and BMD measurements of patients with PHPT were evaluated retrospectively. Expressions of p27Kip1 and CaSR were decreased in parathyroid adenomas, compared to normal glands (p < 0.05). High intensity of CaSR staining (3+) was more frequent in normal parathyroid tissue (75%) than adenomas (12%) (p < 0.01). Hypertension was not observed in patients with high staining intensity of CaSR (p = 0.032). There was a negative association between CaSR expression and body mass index (BMI) (p = 0.027, r = - 0.313). There was no significant relationship between p27Kip1 and CaSR expressions, serum calcium, plasma parathormone, 25-hydroxy vitamin D levels, and bone density (p > 0.05). The expressions of p27Kip1 and CaSR were decreased in PHPT patients. This reduction may play an important role in the pathogenesis of PHPT. However, neither p27Kip1 nor CaSR expression was found to be useful in predicting prognosis or severity of disease.

Diffuse Neuroendocrine Cell Hyperplasia: Report of Two Cases.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disorder characterised by a proliferation of neuroendocrine cells within the lung. It is believed that a minority of the patients with DIPNECH can develop carcinoid tumors. Here, we report two new cases of DIPNECH with coexisting carcinoid tumors.

Gastric metastasis of ectopic breast cancer mimicking axillary metastasis of primary gastric cancer.

Ectopic breast tissue has the ability to undergo all the pathological changes of the normal breast, including breast cancer. Gastrointestinal metastasis of breast cancer is rarely observed and it is very difficult to differentiate gastric metastases from primary gastric cancer. We present a case of 52-year-old female, who suffered from abdominal pain. Physical examination showed a palpable mass in the left anterior axilla and computerized tomography revealed gastric wall thickening with linitis plastica. When gastroscopic biopsy showed no signs of malignancy, excisional biopsy was performed in the left axilla. Histological examination revealed invasive lobular carcinoma of the breast, consistent with ectopic breast cancer. Further gastroscopic submucosal biopsies and immunohistochemical studies revealed gastric metastases of invasive lobular carcinoma. Axillary ectopic breast tissue carcinomas can mimic axillary lymphadenopathies. Additionally, gastric metastasis of breast cancer is an uncommon but possible condition. To the best of our knowledge, this is the first report of ectopic breast cancer with gastric metastasis.