Primary bone xanthoma of the inferior orbital rim.

Primary bone xanthoma is an extremely rare benign bone tumor histologically characterized by mononuclear macrophage-like cells, abundant foam cells, and multinucleated giant cells. Xanthomas of the bone usually appear as a benign secondary manifestation of some diseases. Therefore, they are denominated primary xanthomas when the other diseases are discarded.We report a peculiar case of primary bone xanthoma of the inferior orbital rim in the absence of hyperlipidemic conditions. Surgical intervention was performed under local anesthesia via a subtarsal 1-cm incision. Histopathological examination confirmed the diagnosis of bone xanthoma. Primary bone xanthomas are extremely rare. Diagnosis of such lesions is challenging and requires both radiographic and histopathological features assessment. A careful work-up and a full lipid profile should be performed to rule out underlying diseases.

Oral hyaline ring granuloma.

Hyaline ring granuloma is a rare oral lesion with an unclear and controversial etiology, characterized by the presence of rings of palely eosinophilic structureless material (the so-called hyaline rings) with multinucleated giant cells around and within the very same rings.Various theories have been proposed about the pathogenesis of hyaline ring granulomas. Many authors consider a vegetable origin, suggesting that it may represent a reaction to foreign material such as food (and in particular pulses). Instead, other authors deny this possibility, proposing that the hyaline rings might represent degenerated blood vessels, degenerated collagen, or fibrosed extravasated serum proteins.The aim of this article is to present a case of hyaline ring granuloma and to briefly review the literature.

New onset sarcoidosis following biologic treatment in patients with seronegative inflammatory arthritis: A case series and systematic literature review.

OBJECTIVE: To report cases of new onset sarcoidosis upon biologic (bDMARDs) treatment administration in patients with seronegative inflammatory arthritis in a real-life cohort, alongside a systematic literature review (SLR) on this topic. METHODS: We performed a retrospective analysis on clinical records of patients with seronegative arthritis followed up in a monocentric cohort who underwent bDMARDs treatment due to the underlying rheumatic disease and described any newly diagnosed sarcoidosis in this cohort. Only ascertained cases with available radiological and/or histological documentation were considered. A SLR on new-onset sarcoidosis in seronegative arthritis receiving bDMARDs was performed across MEDLINE (through PubMed), Scopus and Ovid (Cochrane, Embase) electronic databases using appropriate strings. RESULTS: In our cohort, 4 new-onset cases of sarcoidosis were reported among patients with seronegative inflammatory arthritis receiving biologics. Three out of 4 patients were receiving anti-tumor necrosis factor alpha (TNFα) while 1 patient was on secukinumab (anti-IL17A) prior to sarcoidosis onset. The SLR disclosed 46 new-onset sarcoidosis cases upon biological treatment for seronegative arthritis, of whom 43 occurred during treatment with anti-TNFα, while 3 during anti-IL-17A therapy. In our cohort as well as in the majority of cases reported in the SLR, sarcoidosis presented with lymph nodal and lung involvement and displayed a benign course with spontaneous resolution in about 1 fourth of the cases. CONCLUSION: The use of biologics may relate to the onset of sarcoidosis; hence, clinicians must remain aware of the potential occurrence or reactivation of sarcoidosis when starting biologic treatment in patients with inflammatory arthritis, performing adequate patient assessment and surveillance. Since TNFα inhibitors may represent a therapeutic option for sarcoidosis, further evaluation on larger cohorts is needed to investigate any causal link with the development of sarcoidosis.

Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome.

BACKGROUND: MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. CASE PRESENTATION: We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. CONCLUSIONS: Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves.

Review of 43 osteomas of the craniomaxillofacial region.

PURPOSE: To present and discuss the demographic and clinical aspects and the management of 44 cases of osteomas of the craniomaxillofacial region. MATERIALS AND METHODS: A retrospective chart review was performed of all cases of osteoma diagnosed from 2000 through 2010. The data collected included age at diagnosis, gender, lesion location, presenting symptoms, type of osteoma, treatment, and outcomes. RESULTS: Forty-two patients with 43 osteomas were diagnosed during the study period. Their mean age was 48 years. The male-to-female ratio was 0.4:1. Twenty-one patients were asymptomatic, whereas 10 patients complained about headache and neuralgia, and 11 patients presented with facial asymmetry. Only 21 symptomatic osteomas were surgically removed after histologic diagnosis, whereas for the asymptomatic lesions a careful follow-up was maintained. CONCLUSIONS: The slow growth of osteomas allows a conservative attitude toward asymptomatic lesions. Thus, when surgery is performed, it is extremely important to plan a surgical approach that minimizes any damage to the adjacent structures.

Nodular fasciitis in the maxillary region.

We describe the imaging and histologic findings of a case of nodular fascitiis in the maxillary region in a 54-year-old man. The rapid growth and tissue distortion of this lesion may mimic malignant tumors. Therefore, proper diagnosis is essential to avoid unnecessarily aggressive treatment.

Immunohistochemical Markers and TILs Evaluation for Endometrial Carcinoma.

OBJECTIVE: The molecular classification for endometrial cancer (EC) introduced by The Cancer Genome Atlas Research Network (TCGA) and the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) proved the existence of four molecular prognostic subtypes; however, both classifications require costly technology. We suggest a prognostic model for EC based on immunohistochemistry (IHC) and tumor-infiltrating lymphocytes (TILs). STUDY DESIGN: One hundred patients were included. We retrospectively investigated IHC prognostic parameters: mismatch repair (MMR)-deficient tumors, p53 mutation status, progesterone receptors (PgRs), and estrogen receptors (ERs). We further evaluated TILs. These parameters were related to the clinical and morphological features and to the outcome. RESULTS: We classified tumors into three groups (IHC analysis): MMR-deficient, p53-mutated, p53 wild-type. MMR-deficient tumors had a good prognosis, p53 wild-type tumors an intermediate one, and p53-mutated tumors had the poorest outcomes. Disease-free (DFS) and overall survival (OS) were significantly better among PgR+ tumors (respectively p = 0.011 and p = 0.001) and PgR expression is an independent prognostic factor for a better DFS frommultivariate analysis (OR = 0.3; CI: 0.1-0.9; p = 0.03).No significant correlation was observed between DFS and TILs. However, among MMR-deficient tumors, the mean value of TILs was higher than among the other tumors(111 versus 71, p = 0.01) Conclusions: The prognostic model based on IHC markers could potentially be a valid and applicable alternative to the TCGA one. The PgR determination could represent an additional prognostic factor for EC.

Clinical, Sonographic, and Hysteroscopic Features of Endometrial Carcinoma Diagnosed after Hysterectomy in Patients with a Preoperative Diagnosis of Atypical Hyperplasia: A Single-Center Retrospective Study.

BACKGROUND: atypical endometrial hyperplasia (AEH) is a precancerous condition implying a high risk of concurrent endometrial cancer (EC), which might be occult and only diagnosed at postoperative histopathological examination after hysterectomy. Our study aimed to investigate potential differences in preoperative clinical, sonographic, and hysteroscopic characteristics in patients with AEH and postoperative diagnosis of EC. METHODS: a retrospective single-center study was carried out on a case series of 80 women with AEH undergoing diagnostic workup, including ultrasonography and hysteroscopy, with subsequent hysterectomy. Women with AEH confirmed at the histopathological examination were compared with patients with a postoperative diagnosis of EC. RESULTS: in our population, EC was diagnosed in 53 women, whereas the preoperative diagnosis of AEH was confirmed in 27 cases. At ultrasonography, women with occult EC showed greater endometrial thickness (20.3 mm vs. 10.3 mm, p 0.001) and size of the endocavitary lesion (maximum diameter 25.2 mm vs. 10.6 mm, p 0.001), and a higher prevalence of irregular endometrial-myometrial junction (40.5% vs. 6.7%, p 0.022) and endouterine vascularization at color Doppler (64.2% vs. 34.6%, p 0.017). At hysteroscopy, patients with occult EC showed a higher prevalence of necrosis (44.2% vs. 4.2%, p 0.001) and atypical vessels (70.6% vs. 33.3%, p 0.003), whereas true AEH mainly presented as a protruding intracavitary lesion (77.8% vs. 50.9%, p 0.029). In EC, subjective assessment by the operator was more frequently indicative of cancer (80.0% vs. 12.5%). No difference was found for clinical variables. CONCLUSIONS: occult EC in AEH may exhibit some differences in ultrasonographic and hysteroscopic patterns of presentation compared with real AEH, which could prompt a more significant suspect for the possible presence of concurrent EC at preoperative diagnostic workup.

Neuroendocrine tumors of the thymus.

Neuroendocrine tumors of the thymus (NETTs) are unusual thymic neoplasms that were misdiagnosed as thymomas until the 1970s, when they eventually acquired a distinct identity. No collective large series have been published so far, and information about clinical presentation, diagnosis, histology, and treatment is derived from analysis of the case series and case reports published over a long period. NETTs are more aggressive than their pulmonary and abdominal counterparts, presenting at a more advanced stage, often with distant metastases, and are associated with poor long-term survival. Most patients are symptomatic at presentation as a result of the local invasion. Twenty percent to 30% of the cases are associated with endocrine disorders, mostly Cushing syndrome and multiple endocrine neoplasia syndrome. There is no official staging system for these tumors and investigators rely on the Masaoka staging system used for thymomas. Histologically, 2 classification are used: the World Health Organization and the Armed Forces Institute of Pathology classifications. Histologically, most tumors show moderately to poorly differentiated histologic features, reflecting their aggressive clinical behavior. Surgery is the most effective treatment option, although the aggressiveness of the tumor often requires extensive resection. Chemotherapy and radiotherapy may be used either preoperatively or postoperatively, although the small number of patients does not allow the design of standard guidelines about optimal schedules and doses. Survival depends on stage at presentation, histologic degree of differentiation, associated endocrine syndromes, and resectability rate. Recurrences are frequent after surgery and may be locoregional or distant. Surgery is recommended when feasible in the treatment of locoregional recurrences.

Diagnosis and surgical treatment of a nasolabial cyst.

Nasolabial cysts are uncommonly diagnosed nonodontogenic soft tissue lesions located close to the nasal alar region of the face, presenting as extraosseous swelling in the region of the nasolabial fold. Nasolabial cysts are likely to remain undetected unless and until they become infected or are associated with facial deformity. Histologically, it is lined with nonkeratinized squamous epithelium or, more frequently, with respiratory-type cylindrical epithelium with goblet cells. The aim of this article was to present and discuss the surgical management of a case of nasolabial cyst and to briefly review the literature.

Surgical treatment of glandular odontogenic cysts.

Glandular odontogenic cyst (GOC) is an unusual entity of jaws, which shows features that overlap with botryoid odontogenic cyst and mucoepidermoid tumor. Glandular odontogenic cyst has an uncertain histogenesis and was recently listed by the World Health Organization as a developmental odontogenic epithelial cyst: it is characterized by an epithelial lining with cuboidal or columnar cells, both at the surface and lining, with crypts or cystlike spaces within the thickness of the epithelium. The radiographic appearance of GOC varies and is not pathognomonic. Several methods of treatment of GOC including curettage, enucleation, and en bloc excision have been used. The recurrence rate of GOC described in literature varies between 21% and 55% according to the different treatment options. We report 2 patients with GOC, describe their clinicopathologic aspects, and discuss the treatment modalities in relation to 2 different clinical situations.

Mucoepidermoid carcinoma of the lacrimal sac masquerading as dacryocystitis.

Tumors originating from the lacrimal sac are exceedingly rare. They may mimic chronic inflammation and be misdiagnosed, delaying treatment and allowing the tumor to devastate the visual system. Mucoepidermoid carcinoma has been described only occasionally. We report a case that presented with unusual diagnostic and treatment aspects. A 33-year-old Italian man had tearing in his right eye. The initial presentation mimicked dacryocystitis, and the patient had been treated with antibiotics and steroids, without results. Consequently, an external dacryocystorhinostomy was performed, during which an open biopsy specimen was taken; it suggested the presence of a basocellular epithelioma. Computed tomography, magnetic resonance imaging, and further biopsies led to the diagnosis of squamous carcinoma of the lacrimal sac. On this basis, the patient underwent preoperative radiation (41.4 Gy) and conservative surgical resection of the tumor, with preservation of the eye and extraocular muscles. The histopathologic examination of the gross surgical specimen led to a final diagnosis of primary mucoepidermoid carcinoma of the lacrimal sac and revealed clear resection margins. The clinical evaluation and positron emission tomography at 6 months showed complete functional recovery and no evidence of the disease. This report highlights the clinicopathologic characteristics and therapeutic uncertainty of this rare tumor.

Surgical treatment of an oral cyst with respiratory epithelium.

Cysts with respiratory epithelium are rare entities in the oral cavity. In the literature, there are only few cases of oral cystic masses lined by respiratory epithelium but lacking gastrointestinal epithelium. In this paper, we present the surgical treatment of a cyst with respiratory epithelium in the floor of the mouth affecting a 35-year-old woman. The asymptomatic lesion was noticed 6 years previously. On histopathologic examination, the cyst showed walls that were composed of connective tissue covered by pseudostratified ciliated columnar epithelium, interspersed by a few goblet cells. Oral cysts lined by respiratory epithelium are benign lesions. Cure is effected by surgical excision. This lesion should be considered in the differential diagnosis of masses involving the anterior tongue or the floor of the mouth.

Traumatic ulcerative granuloma with stromal eosinophilia of the retromolar region.

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare chronic benign lesion of the oral mucosa. Clinically, it may mimic squamous cell carcinoma as well as other malignant lesions. Most cases of TUGSE are reactive. A case of TUGSE of the retromolar region is reported. An asymptomatic ulceration with indurated borders, limited to the gingiva, was localized in the right retromolar region. An incisional biopsy was taken. Six weeks after the biopsy, the residual ulceration spontaneously disappeared. After 6 months of follow-up, the lesion had not recurred.Traumatic ulcerative granuloma with stromal eosinophilia can be interpreted as a subset of lymphoproliferative disorders.A malignant lymphoid proliferation should be suspected when atypical histologic findings and monoclonality are observed. Given the benign nature of TUGSE, overtreatment should be prevented in patients affected by this disease.

Ultrasound-guided fine needle aspiration cytology in the diagnosis of hepatic and pancreatic perivascular epithelioid cell tumors: A case series.

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that can affect any part of the body. They can be sporadic or arise in the setting of tuberous sclerosis (TSC). In this article, we report a series of three hepatic and two pancreatic PEComas diagnosed preoperatively with ultrasound-guided fine needle aspiration (FNA). All patients were female (age range 28-70), had no personal history of TSC and presented with a single, localized painless mass. Rapid on-site evaluation (ROSE) of cytologic samples was performed for all cases to evaluate for cellular content and adequacy of specimens. Direct smears and cell block preparations revealed a proliferation of medium to large polygonal epithelioid cells, with abundant eosinophilic and vacuolated cytoplasm, arranged in sheets and nests. On immunohistochemistry (IHC), neoplastic cells showed co-expression of melanocytic and smooth muscle markers and a diagnosis of PEComa was rendered. PEComas of the pancreas and liver are rare neoplasms, but should always be considered when examining "clear cell" neoplasms, especially in young female patients. If good quality cytologic samples are obtained by FNA, a correct diagnosis can be achieved with the help of IHC. This is of particular importance in order to plan adequate surgical strategy and to avoid overtreatment.

Nipple-Sparing Mastectomy: Reliability of sub-areolar sampling and frozen section in predicting occult nipple involvement in breast cancer patients.

INTRODUCTION: The oncological safety of nipple-areolar complex (NAC) preservation is a concern in the mastectomies performed for cancer indication. The detection of tumor cells during the intraoperative frozen section examination (IE) of sub-areolar/nipple tissue (SAT) leads to the removal of NAC, but frequently the final histology of the nipple is negative for malignancy. This study aims to evaluate the accuracy of SAT examination in predicting occult NAC involvement in case of Nipple-Sparing Mastectomy (NSM). METHODS: The study includes 76 NSM. We evaluated the concordance between histopathologic features of frozen and paraffin-embedded SAT sections. Moreover, we examined the "true margin" (TM), defined as the measurement of the distance between the tumor margin and the edge of the SAT. A margin >1 mm was considered negative. RESULTS: In 26/76 cases the IE of the SAT was positive. At the final histology, the NAC was negative in 57.7% of cases. The concordance between frozen and paraffin section examination of the SAT was 92.1%. The three false-positives were low-grade DCIS at the IE, and negative or DIN1a on permanent section. A negative TM seems to predict for a negative NAC (6/6). CONCLUSIONS: The detection of a low-grade DCIS at the IE of the SAT may not be confirmed at the permanent section examination; we recommend caution in removing the NAC in these cases. The evaluation of the TM may improve the accuracy of SAT analysis in predicting occult NAC involvement; in our series, a TM wider than 1 mm correlates with a negative NAC.

Prognostic value of quantitative analysis of WT1 gene transcripts in adult acute lymphoblastic leukemia.

We quantified Wilm's tumor gene (WT1) using a real time quantitative polymerase chain reaction in 20 adult patients with acute lymphoblastic leukemia at presentation. A WT1 level greater than 906 (median value for the whole series) was a significant predictor of a poor disease-free and overall survival in uni- and multivariate analyses.

Head and neck squamous cell carcinoma: role of the human papillomavirus in tumour progression.

High risk human papilloma viruses (HPVs) have been shown to be independent risk factors for anogenital tract cancers, and have also been detected in head and neck squamous cell carcinomas (HNSCC). The aim of our study was to determine the prevalence of HPV DNA in a group of 47 squamous cell carcinomas of the oropharynx and the oral cavity, and to compare the clinical behaviour of HPV positive and negative tumours. We also assessed the proliferation index, as evaluated by Ki67 immunohistochemistry positivity, and the level of p53 reactivity. HPV DNA was found in 50% of carcinomas of the oropharynx and 36% in those of the oral cavity, the only genotype detected being HPV 16. Patients with HPV-positive carcinomas had a better overall survival than those with HPV-negative carcinomas. Our data suggest that HPV-positive oropharyngeal cancers comprise a distinct disease entity with an improved prognosis.