Lymphocyte-predominant lesional inflammatory infiltrates of the skin are associated with mucosal-dominant phenotype in pemphigus.

INTRODUCTION: Pemphigus is a potentially life-threatening autoimmune blistering disease. To date, studies assessing the association of histopathology with clinical phenotype are lacking. We sought to evaluate the main histopathologic findings and, also, the potential links between cutaneous inflammatory infiltrates and clinical characteristics in pemphigus. METHODS: We conducted a retrospective cohort study in patients diagnosed with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) in a referral center for autoimmune blistering diseases. RESULTS: A total of 124 patients were included in the study (97 had PV and 27 had PF). On biopsy specimens, PV was more frequently associated with the "row of tombstones" feature (36.1% vs. 11.1%, p = 0.013), and PF was associated with acanthosis (44.4% vs. 23.7%, p = 0.034). Acantholysis was found in the upper half of the epidermis in PF (96.3% vs. 5.15%, p < 0.001), as opposed to the lower half in PV (75.2% vs. 0%, p = 0.002). Patients with lymphocyte-predominant inflammatory infiltrates in lesional skin specimens presented with a higher frequency of the mucosal-dominant phenotype (25.5% vs. 9.1%, p = 0.014), higher-density cellular infiltrate (100% vs. 41.6%, p < 0.001), and more frequent acantholytic cells (42.6% vs. 23.4%, p = 0.025). Neutrophil-predominant infiltrates in specimens from lesional skin were linked to a milder disease based on median Pemphigus Disease Area Index (38.9% vs. 13.2%, p = 0.036) and Autoimmune Bullous Skin Disorder Intensity Score (20.2 vs. 36.3, p = 0.019), while eosinophil-predominant inflammatory infiltrates were more often associated with eosinophilic spongiosis (100% vs. 23.1%, p = 0.014). CONCLUSIONS: Lymphocyte-predominant infiltrates in lesional skin specimens of pemphigus patients predict a mucosal-dominant phenotype, while neutrophil-predominant infiltrates are associated with a milder disease.

Neurotoxicity of Bisphenol A and the Impact of Melatonin Administration on Oxidative Stress, ERK/NF-kB Signaling Pathway, and Behavior in Rats.

Bisphenol A (BPA) exposure can be associated with neurodevelopmental disorders due to impairment of cell proliferation and synaptic development. Our study evaluated the effects of melatonin (MEL) on ambulatory activity, lipid peroxidation, cytokines, ERK/NF-kB signaling pathway in the hippocampus and frontal lobe, and histopathological changes in the hippocampus of the BPA-treated rats. The animals were divided into 4 groups: control, BPA, BPA + MEL I, and BPA + MEL II. MEL I (20 mg/kg b.w.) and MEL II (40 mg/kg b.w.) were orally administered for 28 days. On the 29th day, BPA (1 mg/kg b.w.) was intraperitoneally administered, and, after 24 h, an open field test (OFT) and an elevated plus maze (EPM) were conducted. The results showed that the MEL II group made significantly more entries in the open arms of EPM, traveled significantly greater distance, and spent more time in the central part of OFT. Malondialdehyde levels were diminished by MEL II in the hippocampus and by MEL I in the frontal lobe. In the hippocampus, the MAPK level was significantly lowered by both doses of MEL (p < 0.05) while in the frontal lobe, only MEL II reduced the MAPK activation. MEL I and II significantly decreased the γH2AX and upregulated the NFkB and pNFkB expressions in the hippocampus while MEL II downregulated the MCP1 expression. Both doses of MEL attenuated the BPA-evoked histopathological alterations in the hippocampus. These data indicate that MEL can mediate the neuroprotection against BPA-induced neurotoxicity and improves behavioral changes suggesting a real potential as a protective agent in brain toxicity.

Risk factors for positive sentinel lymph node, lymphatic or hematogenous dissemination over time in patients with cutaneous melanoma.

The aim of the present study was to assess the influence of localization, age or sex and histopathological characteristics upon the chance of developing lymphatic or hematogenous metastatic spread over time, or a positive sentinel lymph node in cutaneous melanoma patients. Patients from the Department of Dermatology, County Emergency Hospital Cluj-Napoca (Cluj-Napoca, Romania), presenting with cutaneous melanoma confirmed histopathologically and a SPECT/CT or lymphoscintigraphic examination to detect the sentinel lymph node, were included in the present study. Our results revealed that Breslow index >2 mm [odds ratio (OR)=4.22, 95% confidence interval (CI) (1.12; 15.93)], presence of ulceration [OR=6.01, 95% CI (1.87; 19.35)], and positive sentinel lymph node [for at least one sentinel lymph node OR=3.58, 95% CI (1.06; 12.04)] were risk factors for hematogenous metastases. All these, except for the Breslow index >2 mm, were demonstrated to be a risk factor for lymphatic spread metastases over time. Ulceration and male sex also represented risk factors for a positive sentinel lymph node, men having a higher risk of developing sentinel lymph nodes than women [adjusted OR=2.27, 95% CI (1.00; 5.13)]. In conclusion, the predictors that influence the occurrence of lymphatic or hematogenous metastases may differ, ulceration and positive sentinel lymph node being common for both types of metastatic spread, while Breslow index being a significant predictor only for hematogenous metastases. Male sex and the presence of ulceration were demonstrated to be significant risk factors for positive sentinel lymph nodes.

Silicone Adenopathy and Intractable Axilary Pain after Breast Implant Augmentation - Case Report.

Introduction: Silicone lymphadenophaty (siliconoma) is a rare complication secondary to breast implant augmentation or breast reconstruction surgery. Although it is usually linked to the age of the implant, the predominant etiology is multifactorial. Herein, we report a case of extensive siliconoma in the axilla in the hope that our experience will contribute to clinical decision making. Case presentation: We report the case of a 41-year-old woman with intense pain in her right axilla 20 years after breast augmentation surgery. Analgesics were of limited use and the pain became debilitating over time. After a thorough physical examination, imaging studies found three central axillary lymph nodes with a "snowstorm" appearance, suggestive of silicone lymphadenopathy. A complete excision of the lessions was performed with resolution of pain on follow-up. Subsequent histological analysis showed lymph nodes containing large doplets of silicone. Conclusions: General and plastic surgeons must remain aware as silicone adenopathy can be causative of anxiety and significant local symptoms among patients. Thorough investigations are needed in order to exclude malignancies and provide an optimal treatment strategy.

Transesophageal endoscopic ultrasound fine needle aspiration of vertebral body osteolytic tumors - a novel diagnostic approach. Case series.

AIMS: Vertebral lesions, either primary or more frequently metastasis, are difficult targets for percutaneous guided biopsies and surgical biopsies and are associated with greater risks of complications. We investigated the feasibility of endoscopic ultrasound (EUS) fine needle aspiration (FNA) biopsy in the assessment of vertebral osteolytic tumors as an alternative to CT guided biopsy which is the technique currently used. MATERIAL AND METHODS: Four patients with osteolytic tumors of the vertebral bodies identified by imaging methods (CT or MRI) - 3 patients, and one with a tumor detected primarily during EUS procedure were included in order to evaluate the feasibility of the procedure. The lesions were located either at the dorsal or lumbar vertebrae. In all cases we performed EUS FNA of the osteolytic vertebral body lesions with 22G needles using the transesophageal or transgastric approach. RESULTS: In all cases EUS FNA provided enough tissue for an accurate histopathological report, with no procedural complication. We diagnosed lung adenocarcinoma, hepatocarcinoma and a pancreatic adenocarcinoma vertebral metastasis and one case of lymphoma. CONCLUSIONS: EUS FNA is a valuable technique which should be considered in selected cases, when a "traditional approach" is not applicable or associated with a higher risk. Treatment guidelines are based on the histology of the tumor, histopathological examination being nowadays mandatory. Therefore, we propose for selected cases a feasible technique, with significantly lower procedural risks, as an alternative for open surgical biopsies or computed tomography guided biopsies.

Nipple Ultrasound: A Pictorial Essay.

Ultrasound (US) is an attractive diagnostic approach to identify both common and uncommon nipple pathologies, such as duct ectasia, nipple abscess, nipple leiomyoma, nipple adenoma, fibroepithelial polyp, ductal carcinoma in situ (restricted to nipple), invasive carcinoma, and Paget's disease. US is the reliable first-line imaging technique to assess nipple pathologies. It is useful to identify and characterize nipple lesions. Additionally, we have presented the mammography and MRI outcomes correlated with histopathologic features for the relevant cases.

Upper gastrointestinal involvement in systemic sclerosis: Findings in a real-life setting.

Gastrointestinal tract involvement is the most common visceral affectation in systemic sclerosis (SSc), but the manifestations may vary in extension and severity. Endoscopic and histopathological gastroesophageal findings were investigated in patients with SSc. A total of 79 consecutive patients with definite SSc were enrolled in a cross sectional study. Clinical data were collected, upper gastrointestinal endoscopy and biopsies from gastric mucosa were performed in all cases. Fifty-seven (72.1%) out of 79 SSc patients had gastroesophageal symptoms. The most frequent were dysphagia, present in 33 (41.7%) and gastroesophageal reflux symptoms in 23 (29.1%) patients. Out of the 79 patients, 22 were asymptomatic, but in 16 esophageal and gastric mucosa changes were endoscopically detected. Reflux esophagitis was found in 39 (49.3%) patients. The presence of esophageal manifestations was not related to the disease duration or with its other variables. Signs of gastritis were endoscopically described in 47 (59.4%) and confirmed on histopathologic examinations in 45 patients. In 31 patients without any endoscopic changes, 18 (22.7%) showed signs of gastritis on histopathologic examination. No significant statistical differences were found between symptomatic and asymptomatic patients or between those with limited cutaneous SSc and those with diffuse cutaneous SSc in terms of clinical, endoscopic or histopathological findings, except the higher proportion of hiatal hernia in symptomatic patients. The results of this study might suggest that upper gastrointestinal endoscopy should be performed during the early stage of the disease and then periodically in patients diagnosed with SSc, even in the absence of typical symptoms.

Pectoralis muscle metastases from breast cancer in a young patient detected by automated breast ultrasound.

Metastases to the skeletal muscle from breast cancer represent an unusual and rare condition. We present the case of a 27-year-old female with left breast cancer (IDC NST G3) who underwent neoadjuvant chemotherapy followed by conservativesurgery (sectorectomy and lymphadenectomy) and radiation therapy. Two months after the end of radiotherapy she presented with a 2 mm skin lesion and she was referred for a screening ultrasound. The screening automated breast ultrasound (ABUS) revealed local recurrence and pectoralis metastases, lesions evaluated also by magnetic resonance imaging. The diagnosis was confirmed by the ultrasound-guided biopsy.

Ulcerative colitis associated with gastric heterotopia in the rectum: a case report.

Gastric heterotopia is defined as the presence of morphologically normal gastric tissue at a non-physiological site, coexisting with the original tissue. Although it is not uncommon to see it in the esophagus, duodenum or small intestine, it is exceptionally rare to discover gastric mucosa in the rectum. Here we report the case of a 46-year old male with a 10-year history of ulcerative colitis in whom the surveillance rectosigmoidoscopy detected a Mayo score of 1 for ulerative colitis activity and a middle rectal sessile polyp. Pathological examination revealed an active chronic colitis, and rectal mucosa with heterotopic gastric mucosa composed of oxyntic glands was depicted. A month later, the patient was reevaluated and endoscopic mucosal resection was performed. Histology confirmed the gastric body type mucosa co-mingling with rectal mucosa.

Fibroadenomas and breast carcinoma: a possible answer to a frequently asked question. A pictorial essay.

Fibroadenomas (FAs) are the most frequently encountered benign breast lesions in young women and due to the age of the patients, they are usually diagnosed by ultrasound. Although they rarely undergo malignant transformation, the patients remain concerned about the possibility of malignant transformation. The aim of this pictorial essay is to illustrate the appearance of classic and complex fibroadenomas, to discuss the risk factors and to highlight the imaging characteristics that raise the suspicion of malignant transformation. In other words, we try to answer, according to our experience and literature data, to a frequently asked question in daily practice: "Is there any risk thatmy fibroadenoma will become malignant?"

Tracheal enlargement or Mounier-Kuhn syndrome in giant cell arteritis: a possible causal association with therapeutic implications.

Giant cell arteritis (GCA) is a large-vessel vasculitis with rarely described respiratory initial manifestations. We report such a case presenting with hoarseness, stridor, cough and dyspnea, in which a tracheomegaly with tracheomalacia was found. No signs of relapsing polychondritis were present. The respiratory symptoms rapidly improved after glucocorticoids and Azathioprine. Tracheomegaly or Mounier-Kuhn syndrome is characterized by marked dilatation of trachea and central bronchi. The differential diagnosis and the possible relationship between tracheomegaly and GCA involving metalloproteinase-induced elastolysis are discussed. This is the first case, to our knowledge, of Mounier-Kuhn syndrome in vasculitis. The association of tracheomegaly with GCA may be underestimated, as the diagnosis is not always obvious on conventional radiographs. A tracheal enlargement finding in GCA requires monitoring to ensure early detection and prevention of spontaneous tracheal rupture. Adding a metalloproteinase inhibitor like Doxycycline to GCA therapy would be rational for the prophylaxis of complications.

Polyarteritis Nodosa in Pregnancy.

BACKGROUND: Polyarteritis nodosa (PAN) is a rare disease that occurs predominantly in middle-aged males; its onset during pregnancy is exceptional. CASE REPORT: We present a case of PAN with peripartum onset in a patient with a twin pregnancy after ovarian stimulation for primary infertility. The pregnancy outcome was good in terms of the children's health. In the case of the mother, however, the presence of nonspecific signs and symptoms, a noncontributory ovarian biopsy, and mimics of a puerperal infection delayed the diagnosis of PAN. The emergence of a tender subcutaneous nodule on the forearm and its histopathologic findings were diagnostic. Treatment with pulse methylprednisolone and intravenous cyclophosphamide resulted in the patient's prompt recovery. CONCLUSION: We present the case to stress the value of careful physical examination in unveiling the presence of a rare disease.

Redundant plantar skin folds.

A 46-year-old female patient presented with photosensitivity, symmetric arthritis, episodic plantar pain and strikingly redundant plantar skin folds, likely due to lipoatrophy after recurrent episodes of plantar panniculitis. In this context, leukopenia with lymphopenia, thrombocytopenia and positive antinuclear antibodies were revelatory for systemic lupus erythematosus. However, a small cerebriform plantar collagenoma, along with discrete dysmorphic features with downslanting palpebral fissures and mild right ptosis, second and third syndactyly and a larger first right toe since childhood, and early-onset bilateral ovarian cystadenoma, suggested a minimal Proteus syndrome. Genetic confirmation could not be performed. As adipose tissue dysregulation may be a feature of Proteus syndrome, the possible mechanisms leading to localized lipoatrophy in this setting are discussed. This case enlights intriguing links between adipogenesis, inflammation and dysmorphology. From a practical point of view, finding and treating an over-imposed inflammation could help limit damage in a hamartomatous syndrome.

Unilateral temporal myositis heralding polymyositis: ultrasonographic and elastographic findings. Case report.

Temporal myositis is a rare inflammatory disease of the temporal muscle. We report a case of unilateral temporal myositis, in which a polymyositis was diagnosed two years thereafter. Although focal myositis may rarely herald polymyositis, isolated temporal myositis preceding inflammatory myopathies has not been described, to our knowledge. In the setting of a temporal pain and swelling, ultrasonography may help in diagnosis, biopsy guidance, disease extension, and progression assessment. Further studies are necessary to establish the role of elastography in differentiating between muscle inflammation and hypertrophy.

Clinico-pathologic, dermoscopic and ultrasound examination of a rare acral tumour involving the nail - case report and review of the literature.

There is a large spectrum of tumors presenting as nodular lesions that may affect the subungual space. We report the case of a 62-year-old woman presenting with a rapidly growing nodular lesion under the nail of the first left toe. Non-invasive examinations using dermoscopy, ultrasonography and elastography were performed for the preoperative assessment of the lesion. The biopsy of the lesion revealed superficial acral fibromyxoma, a benign tumor with predisposition for acral sites. The patient underwent radical surgery with wide resection margins. This is the first case report of a superficial acral fibromyxoma affecting the subungual region characterized by dermoscopic, ultrasonographic and elastographic features. We also performed a short review of the literature.

Breast Involvement in Pure Cutaneous Rosai-Dorfman Disease: Ultrasound and Sonoelastography Appearance With a Review of the Literature.

Rosai-Dorfman disease or sinus histiocytosis of the lymph nodes is a rare, idiopathic, and benign disorder. Painless lymphadenopathy is the most frequent systemic presenting symptom and involves the cervical region in up to 90% of the patients. Extranodal involvement is less common and can represent the initial or the only presentation of the disease. We present the ultrasound and sonoelastographic features of a case of extranodal, pure cutaneous Rosai-Dorfman disease involving the breast, in which the breast involvement led to the final diagnosis. We discuss the ultrasound appearance of the disease (on B-mode, Doppler ultrasound, and sonoelastography) with a review of the literature and the different morphological patterns encountered in extranodal and cutaneous involvement.

Assessment of Cutaneous Melanoma by Use of Very- High-Frequency Ultrasound and Real-Time Elastography.

OBJECTIVE: The primary objective of this study was to evaluate the usefulness of very-high-frequency ultrasound as tool for assessment of skin melanoma by investigation of the correlation between the ultrasound measurement of the thickness of a melanoma and the histopathologically measured Breslow index. The secondary objective was to assess the potential role of real-time elastography in the preoperative evaluation of skin melanoma. SUBJECTS AND METHODS: The study included 42 cutaneous melanoma lesions in 39 adult subjects examined in the division of ultrasound of a department of radiology between September 2011 and January 2015. Gray-scale sonographic features at 40 MHz (thickness, echogenicity, contour) and real-time strain elastographic (qualitative and semiquantitative, strain ratio) characteristics were evaluated and compared with the pathologic results. RESULTS: The melanoma lesions had a homogeneous hypoechoic appearance with a regular contour and stiff or medium consistency. The mean difference between Breslow index and ultrasound thickness was -0.05 mm (95% CI, -0.24 to 0.13 mm), sustaining the absence of significant differences between these two measurements. A strong relation was identified between real-time elastographic appearance and strain ratio for the relations between lesion and hypodermis and between lesion and neighboring dermis (p < 0.002) or hypodermis. CONCLUSION: Our study showed that very-high-frequency ultrasound and real-time elastography can be useful examinations for comprehensive preoperative evaluation of cutaneous melanoma.

Diffuse cutaneous bullous mastocytosis with IgM deposits at dermo-epidermal junction.

Cutaneous mastocytosis is a disease characterized by the infiltration and proliferation of mast cells in the skin. In children, the most common form of presentation is urticaria pigmentosa, while the diffuse cutaneous bullous mastocytosis is one of the rarest subtypes seen. The aim of this paper is to present a case of diffuse bullous mastocytosis with detection of IgM deposits at dermo-epidermal junction using direct immunofluorescence (DIF) microscopy. The diagnosis of diffuse bullous mastocytosis is a challenge, and DIF microscopy is necessary in order to exclude an autoimmune bullous disorder. However, IgM deposits at dermo-epidermal junction can be nonspecific, being found in a variety of skin disorders. A 6-month-old girl presented with bullous lesions and erosions on the scalp and the trunk. During hospitalization, further bullous lesions appeared, along with generalized erythrodermia. Skin biopsy revealed aspects of urticaria pigmentosa. Taking into account the clinical findings, the case was enclosed as bullous mastocytosis. Treatment included the avoidance of trigger factors, and administration of antihistamines along with a short-term course of systemic steroids. The evolution was favorable, with remission of the existing lesions and without occurrence of new ones.

Doppler ultrasound and strain elastography in the assessment of cutaneous melanoma: preliminary results.

AIM: To study the usefulness of color or power Doppler ultrasound (US) in the pre-surgical evaluation of skin melanoma, and to correlate the Doppler characteristics with the appearance on high frequency ultrasound strain elastography (SE) in the preoperative evaluation of cutaneous melanoma. MATERIALS AND METHOD: The study included 42 cutaneous melanoma lesions in 39 adult subjects examined between September 2011 and January 2015. Doppler US features (the presence and aspect of vascularization, and the number of vascular pedicles) and elasticity by strain elastography were evaluated together with the pathological results. RESULTS: The melanoma lesions presented hyper-vascularization, with multiple vascular pedicles and stiff appearance. Significant correlations between the thickness of the tumor, measured histopathologically by the Breslow index, and the degree of vascularization (p=0.0167), and number of vascular pedicles (p=0.0065) were identified. Strong correlations between the SE appearance and vascularization on one hand, and SE and the number of vascular pedicles were also identified (p<0.001). CONCLUSION: Our study demonstrates that Doppler US and SE offer useful information for THE preoperative evaluation of cutaneous melanoma and may contribute to better defining the long term prognosis.