Rapidly evolving pelvic lymphangioleiomyomatosis (LAM) mimicking bilateral hydrosalpinx: report of a rare case and literature review.

Lymphangioleiomyomatosis (LAM) represents a rare neoplasm affecting almost exclusively women of reproductive age. This condition mainly affects the lungs, but extrapulmonary locations such as the pelvis and the retroperitoneum are possible. Clinical evaluation and ultrasound imaging are usually non-specific, and the diagnosis is obtained through surgical excision and histopathological examination. We report a very rare case of abdominal LAM in a young female patient. A thorough literature review of this rare condition with emphasis on gynecologic implications will be presented. The patient was referred for gynecologic consultation due to pelvic pain and infertility. Unfortunately, despite prompt diagnosis and treatment, the course of the disease was severe and led to patient's exitus in a short time. We encountered an extremely rare deadly pathology mimicking a very common gynecologic condition. The gynecologist must always be alert of possible unexpected conditions that will require prompt attention.

Serrated Colorectal Lesions: An Up-to-Date Review from Histological Pattern to Molecular Pathogenesis.

Until 2010, colorectal serrated lesions were generally considered as harmless lesions and reported as hyperplastic polyps (HPs) by pathologists and gastroenterologists. However, recent evidence showed that they may bear the potential to develop into colorectal carcinoma (CRC). Therefore, the World Health Organization (WHO) classification has identified four categories of serrated lesions: hyperplastic polyps (HPs), sessile serrated lesions (SSLs), traditional serrated adenoma (TSAs) and unclassified serrated adenomas. SSLs with dysplasia and TSAs are the most common precursors of CRC. CRCs arising from serrated lesions originate via two different molecular pathways, namely sporadic microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP), the latter being considered as the major mechanism that drives the serrated pathway towards CRC. Unlike CRCs arising through the adenoma-carcinoma pathway, APC-inactivating mutations are rarely shown in the serrated neoplasia pathway.

A novel BRD4-LEUTX fusion in a pediatric sarcoma with epithelioid morphology and diffuse S100 expression.

Malignant epithelioid soft tissue tumors encompass a wide spectrum of lesions. Among them, Epithelioid Malignant Peripheral Nerve Sheath Tumors (MPNST) constitute a distinct subgroup, accounting for <5% of all MPNST. Epithelioid MPNST are infrequently associated with neurofibromatosis type 1, occasionally arise in a schwannoma and show diffuse S100 and CD34 expression, often combined with INI-1 loss. However, the molecular mechanisms underlying the tumorigenesis of epithelioid MPNST remain largely unknown. We describe a case of a 10-year-old girl with an epithelioid malignancy of the orbit. The tumor proved positive for S100, CD34 and SOX10, and, although INI-1 expression was maintained, the overall features suggested the possibility of an epithelioid MPNST, arising in an unusual location. NGS analysis revealed a novel in-frame BRD4-LEUTX fusion gene. LEUTX plays an important role in embryonal genome activation and its expression is mostly suppressed postnatally. We were able to detect increased levels of LEUTX transcript in the tumor, indicating that BRD4-LEUTX fusion leads to LEUTX re-activation. To our knowledge, this fusion has never been reported previously. Whether the current case represents an example of epithelioid MPNST or a distinct tumor entity remains to be determined.

Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet.

BACKGROUND & AIMS: We studied the prevalence of functional abdominal pain disorders (FAPDs) and functional constipation (FC) in a large prospective cohort of children with celiac disease on a strict gluten-free diet (GFD). METHODS: We performed a prospective cohort study, from 2016 through 2018, in a tertiary care center in Italy, of 417 patients (37% male; mean age, 13.7 y) with a diagnosis of celiac disease (European Society for Paediatric Gastroenterology Hepatology, and Nutrition criteria) who had been on a strict GFD for more than 1 year and had negative results from serologic tests after being on the GFD. Parents and children (>10 y) were asked to fill in a questionnaire on pediatric gastrointestinal symptoms, according to Rome IV criteria. Patients' closest siblings (or cousins) who had negative results from serologic test for celiac disease were used as controls (n = 373; 39% male; mean age, 13.5 y). RESULTS: We found a higher prevalence of FAPDs among patients with celiac disease (11.5%) than controls (6.7%) (P < .05); the relative risk (RR) was 1.8 (95% CI, 1.1-3.0). Irritable bowel syndrome (IBS) and FC defined by the Rome IV criteria were more prevalent in patients with celiac disease (7.2% for IBS and 19.9% for FC) than controls (3.2% for IBS and 10.5% for FC) (P < .05 and P < .001, respectively); the RR for IBS was 2.3 (95% CI, 1.1-4.6) and the RR for functional constipation was 2.1 (95% CI, 1.4-3.2). We found no differences in the prevalence of other subtypes of FAPDs. A logistic regression showed that younger age (P < .05) and a higher level of anti-transglutaminase IgA at diagnosis (P < .04) were associated with FAPDs (in particular for IBS) irrespective of GFD duration. CONCLUSIONS: Celiac disease is associated with an increased risk of IBS and FC. Strategies are needed to manage IBS and FC in patients with celiac disease.

Human Leukocyte Antigen (HLA) Haplotype Does Not Influence the Inflammatory Pattern of Duodenal Lymphocytosis Linked to Irritable Bowel Syndrome.

Background and objectives: Duodenal lymphocytosis (DL) is a condition characterized by enhanced infiltration of intraepithelial lymphocytes (IELs) in the duodenal mucosa, and it can be linked to both gluten- and non-gluten-related diseases, such as irritable bowel syndrome (IBS). Materials and methods: We retrospectively selected patients with DL linked to IBS. Formalin-embedded biopsy samples of the duodenum were collected. CD3 lymphocyte immunohistochemistry was used for IELs. The real-time polymerase chain reaction was used to quantify the amount of mRNA coding for tissue transglutaminase 2 (tTG2), interferon-gamma (IFNγ), toll-like receptor 2 (TLR2), and myeloid differentiation primary response 88 (MyD88). All subjects underwent DQ2-8 haplotype analysis. Controls were represented by subjects with IBS without DL. Results: Thirty-two patients with IBS-DL were retrospectively recruited. Fourteen subjects (43.8%) had a DQ2-8 haplotype. DQ2-8 positive subjects had similar levels compared to negative ones for tTG2, IFNγ, TLR2, and MyD88. Cigarette smoke did not influence molecular expression in our study. Smokers had a statistically higher IELs count than non-smokers (54.2 ± 7.7 vs. 36.0 ± 8.8, p < 0.001). A significant, direct correlation between IELs and duodenal expression of IFNγ was found (r = 0.36, p = 0.04). Conclusions: IBS with DL showed higher expression of inflammatory markers than controls, but DQ2-8 haplotype did not seem to affect their expression. Smoking might increase IELs infiltration.

The sharp decline of beta estrogen receptors expression in long-lasting ulcerative-associated carcinoma.

OBJECTIVE: Colorectal carcinoma is an important cause of death in inflammatory bowel diseases, thus requiring surveillance for dysplasia in long-standing ulcerative colitis (UC). Females show a lower incidence probably related to hormonal factors; therefore, a role of estrogen receptors (ERs) has been supposed in carcinoma-associated colitis (CAC) development. Our aim was to identify ER beta/alpha expression in long-lasting pancolitis through each grade of dysplasia to carcinoma and, furthermore, to investigate the simultaneous epithelial apoptosis/proliferation. MATERIALS AND METHODS: Forty-eight patients affected by long-lasting pancolitis were retrospectively investigated. Samples were divided into four groups: UC, low-grade dysplasia/high-grade dysplasia (UC-HGD), and CAC. Normal colon samples were used as controls. ER-beta, ER-alpha, Ki-67, and TUNEL expression (labeling/H index) were evaluated by immunohistochemistry. RESULTS: ER-beta expression revealed an impressive reduction in CAC (10.4 ± 5.1; p < 0.001) compared to controls and UC (34.3 ± 3.1 and 26.8 ± 7.8, respectively), meanwhile ER-beta level in LGD (29.4 ± 3.7) was comparable to UC. As far ER-beta/ER-alpha mean value ratio revealed a progressive reduction. Ki67 demonstrated a progressive significant increase from UC until CAC (37.9 ± 6.4 < 45.7 ± 6.2 < 60.6 ± 5.2 < 71.1 ± 5.1; p < 0.001). Apoptotic index (TUNEL) revealed a strong fall in UC-HGD and CAC. CONCLUSIONS: ER-beta fall could be considered as a biomarker of UC-dysplasia progression. It occurs in HGD and overt neoplasia, while in LGD shows a normal expression. At the moment, we are unable to use this tool in the clinical practice to predict tumor progression, but it would be appropriate to encourage ER expression investigations in large samples for the interesting perspectives of application.

Endocrine Mucin-Producing Sweat Gland Carcinoma: Case Presentation with a Comprehensive Review of the Literature.

(1) Background: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) is a rare, low-grade, neuroendocrine-differentiated, cutaneous adnexal tumor, officially recognized by the World Health Organization (WHO) Skin Tumors Classification in 2018 as a separate entity and homologue of endocrine ductal carcinoma in situ (eDCIS)/solid papillary carcinoma of the breast. Although it is more frequent in the female sex, between 60 and 70 years old, in the peri-orbital region, EMPSGC has also been described in the male sex, in subjects under 60 and over 80, and in extra-eyelid localizations (cheek, temple, scalp), but also in extra-facial localizations (chest and scrotum). (2) Methods: We present the clinical case of a 71-year-old woman with an undated lesion of the scalp, which presented as a nodule, skin-colored, and 2.5 cm in maximum diameter. We also conduct a comprehensive literature review from 1997 to the end of 2022, consulting PubMed, Scopus, Web of Science (WoS), and Google Scholar using the following keywords: "Endocrine mucin-producing sweat gland carcinoma" and/or "EMPSGC" and/or "skin" and "cutaneous neoplasms". In addition, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 253 patients were recorded; 146 were females (57.7%) and 107 were males (42.2%). The vast majority of the lesions were in the eyelids (peri-ocular region), and only a minority of cases involved the cheeks, supra-auricular, retro-auricular, and occipital region, with very rare cases in the scalp, to which the present is also added. (4) Conclusions: The morphological and immunophenotypical features are essential both for the correct diagnosis and to be able to classify this lesion among the corresponding eDCIS/solid papillary carcinoma of the breast, with neuroendocrine differentiation. Recent papers have attempted to shed light on the molecular features of EMPSGC, and much remains to be conducted in the attempt to subtype the molecular profiles of these entities. Future studies with large case series, and especially with molecular biology techniques, will be needed to further add information about EMPSGC and its relationship in the PCMC spectrum.

Kikuchi-Fujimoto disease: a rare case of orbital involvement.

We describe a rare case of orbital involvement in Kikuchi-Fujimoto disease, a rare, benign, self limiting systemic disease, in a young Italian woman. The origin of the disease is unknown, so no specific treatment has been defined. Histology has an important role in establishing the diagnosis. In presence of an eyelid swelling, it is important to rule out infections, lymphoproliferative disorders, and connective tissue diseases. Despite the fact that it is rare in Europe, the possibility of this disease should be borne in mind.

Molecular and ultrastructural analysis of a multiphasic oral malignant melanoma.

Melanomas of the oral cavity are extremely rare. Their rarity and their independence on exposure to UV radiation make them particularly interesting. The authors analyzed an oral multiphasic melanoma composed by a nodular nonpigmented ulcerated central region, a nodular ulcerated pigmented area, a pigmented nonulcerated region, and an area similar to a dysplastic nevus. They determined the expression of some genes involved in the differentiation and cellular transformation in morphologically different regions of melanoma. All these areas were also analyzed by electron microscopy. The various regions composing the melanoma expressed genes involved in melanogenesis and melanoma progression in a different manner. Electron microscopy observation of ultrathin sections of each region evidenced ultrastructural differences, being the cellular architecture more compromised in the most aggressive parts of the neoplasm. This pilot study identified morphological, molecular, and ultrastructural differences that characterize each region of the multiphasic melanoma.

Undifferentiated high-grade pleomorphic sarcoma in a blind eye with a silicone prosthesis implant: a clinico-pathologic study.

PURPOSE: To describe a rare case of an orbital undifferentiated sarcoma arising in an eviscerated eye socket with a silicone implant. METHODS: The clinical and histopathological findings of the case are reviewed and presented. RESULTS: A patient who had undergone post-traumatic evisceration of the right eye and a silicone prosthesis implant 8 years earlier, presented to our observation with a painful eye, on which a brownish, bleeding mass, measuring 1 cm in diameter, was evident. After removal of the silicone prosthesis, the mass was found to arise from the scleral socket. Histopathological analysis demonstrated a malignant tumor composed of markedly pleomorphic cells with a high mitotic rate. An undifferentiated high-grade pleomorphic sarcoma was diagnosed. Complete right orbital exenteration was performed and the patient underwent radiotherapy CONCLUSIONS: This is the first report of an undifferentiated high-grade pleomorphic sarcoma arising from a scleral socket with a silicone implant.

A rare case of primitive epithelioid leiomyosarcoma of the conjunctiva.

PURPOSE: To describe a rare case of conjunctival leiomyosarcoma initially diagnosed as a poorly differentiated squamous cell carcinoma. METHODS: Clinical, light microscopic, immunohistochemical, and ultrastructural findings are reported. RESULTS: A 56-year-old Caucasian woman was referred with a history of a progressive, rapidly growing mass in her left eye. Biopsy of the mass and histology yielded a first diagnosis of a poorly differentiated conjunctival squamous cell carcinoma. Orbital exenteration was performed 2 weeks later. Macroscopically, the exenteration specimen showed a soft mass completely involving the conjunctiva and extending to the eyelids and orbital structures. Histological examination revealed a malignant tumour composed of atypical, predominantly epithelioid large cells. Immunohistochemical and ultrastructural studies combined with the light microscopic findings contributed to clarify the diagnosis of epithelioid leiomyosarcoma. The patient was started on chemotherapy and radiotherapy, but died a few months later from widespread metastases. CONCLUSIONS: primary involvement of the orbit by a leiomyosarcoma is rare, but this eventuality should be considered in the differential diagnosis of rapidly growing orbital and conjunctival masses.

Solitary schwannoma of the rectum mimicking rectal cancer. Report of a case and review of the literature.

A case of a submucosal tumor bulging into the rectum in an old female patient is reported. It proved to be a very rare case of rectal schwannoma, whose differential diagnosis is difficult to obtain preoperatively and optimal treatment and prognosis still uncertain. The mass was removed by means of an ultrasound device after an open anterior rectotomy. The operation was uneventful and the patient is disease free 18 months after.

Neurofibromatosis type 1 and melanoma of the iris arising from a dysplastic nevus: A rare yet casual association?

PURPOSE: We investigated the molecular causes of an unusual pigmented and ulcerated iris lesion detected in a patient diagnosed with neurofibromatosis type 1 (NF1). CASE REPORT: A 52-year-old man was referred to our clinic with a non-traumatic ulcer in his left eye. Hyphema reabsorption disclosed a pigmented iris mass, thus ultrasound biomicroscopy and anterior segment fluorescein angiography were performed to investigate for the presence of a malignant lesion. Upon angiography, the lesion appeared highly vascularized but prevented posterior iris examination. Therefore, a gonioscopy was executed revealing extension of the lesion into the peripheral iris. Histopathology of the excisional iris biopsy revealed iris melanoma over a dysplastic nevus. NF1 is an autosomal dominant disorder characterized by pigmented cutaneous lesions, multiple skin tumors, and spinal and cranial nerve tumors. Uveal melanoma is the most common primary intraocular malignancy in adults. Up to 92% of cutaneous melanomas occur in patients with dysplastic nevus syndrome. Skin melanomas have been found in 0.1%-5.4% of NF1 patients. In literature, only 18 reports of uveal melanoma have been documented in association with NF1, including three cases of iris melanoma. RESULTS: NF1 gene testing identified a causative mutation in the germline but no loss of the wild-type allele in the iris melanoma. CONCLUSIONS: Occurrence of both diseases in one patient is extremely rare, but the common origin of Schwann cells and melanoblasts suggests a non-casual association. Therefore, we propose that NF1 patients should be screened for nevi, both cutaneous and uveal, for better patients' management.

Esophageal Eosinophilia and Eosinophilic Esophagitis in Celiac Children: A Ten Year Prospective Observational Study.

The association between eosinophilic esophagitis and celiac disease is still controversial and its prevalence is highly variable. We aimed to investigate the prevalence of esophageal eosinophilia and eosinophilic esophagitis in a large group of children with celiac disease, prospectively followed over 11 years. METHODS: Prospective observational study performed between 2008 and 2019. Celiac disease diagnosis was based on ESPGHAN criteria. At least four esophageal biopsies were sampled in patients who underwent endoscopy. The presence of at least 15 eosinophils/HPF on esophageal biopsies was considered suggestive of esophageal eosinophilia; at the same time, eosinophilic esophagitis was diagnosed according to the International Consensus Diagnostic Criteria for Eosinophilic Esophagitis. RESULTS: A total of 465 children (M 42% mean age 7.1 years (range: 1-16)) were diagnosed with celiac disease. Three hundred and seventy patients underwent endoscopy, and esophageal biopsies were available in 313. The prevalence of esophageal eosinophilia in children with celiac disease was 1.6% (95% CI: 0.54-2.9%). Only one child was diagnosed as eosinophilic esophagitis; we calculated a prevalence of 0.3% (95% CI: 0.2-0.5%). The odds ratio for an association between eosinophilic esophagitis and celiac disease was at least 6.5 times higher (95% CI: 0.89-47.7%; p = 0.06) than in the general population. CONCLUSION: The finding of an increased number of eosinophils (>15/HPF) in celiac patients does not have a clinical implication or warrant intervention, and therefore we do not recommend routine esophageal biopsies unless clinically indicated.

Clarithromycin-resistant genotypes and eradication of Helicobacter pylori.

OBJECTIVE: To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. STUDY DESIGN: Post hoc retrospective cohort study in a tertiary referral center for pediatric gastroenterology in southern Italy. All 168 children who were positive for Helicobacter pylori were enrolled. Patients had received clarithromycin-based 7-day triple therapy (73 children) or 10-day sequential therapy regimen (95 children). Real-time polymerase chain reaction for assessing clarithromycin resistance was performed on sections of paraffin-embedded gastric biopsy samples. RESULTS: H pylori eradication was achieved in 16 of 32 (50%) children with the A2143G mutation, in 8 of 10 patients with either A2142G or A2142C strains (80%), and in 112 of 116 children with susceptible strains (88.9%). The presence of A2143G mutation was associated with a lower cure rate compared with the rate in the absence of this mutation (50% vs. 89%; P = .001). The sequential regimen achieved a higher cure rate than triple therapy in patients with A2143G mutant strains (80% vs nil; P < .001). CONCLUSIONS: The A2143G mutation confers higher risk of treatment failure. Sequential regimen has higher efficacy than standard therapy, even in children with A2143G mutatant strains.

ERß expression in normal, adenomatous and carcinomatous tissues of patients with familial adenomatous polyposis.

OBJECTIVES: The APC gene mutation triggers familial adenomatous polyposis (FAP) and approximately 80% of sporadic colorectal cancers. FAP summarizes the natural history of colorectal cancer because low- and high-grade dysplastic lesions and adenocarcinoma are simultaneously present in the same patients free from individual and environmental variability factors. Estrogen receptor beta (ERß) has recently been suggested as the most likely mediator of estrogen-related anti-carcinogenic effects in Apc(Min-/+) mice and humans. In this study we assessed the ERß expression in the intestinal mucosa of FAP patients to verify its possible involvement in tumor progression in colorectal cancer. MATERIAL AND METHODS: ERß and ERα expression, cell proliferation (Ki-67) and apoptosis (TUNEL), were evaluated on archival biopsy material from six patients with FAP who underwent colectomy. RESULTS: A progressive significant decrease of ERß expression was observed in the different stages of the disease as compared to normal mucosa (p < 0.001). Interestingly, a decreased ERß expression was directly correlated with apoptosis (r = 0.76, p < 0.001), and inversely correlated with cell proliferation (r = 0.54, p < 0.05). CONCLUSIONS: ERß expression is related to the severity of the disease, supporting the role of ERß as a relevant biomarker of tumor progression and possible chemopreventive target in patients at risk of colonic neoplasia.