Annular erythema as a cutaneous sign of recurrent ductal breast carcinoma, misdiagnosed as erythema chronicum migrans.

Annular erythema as a clinical manifestation of locoregional recurrence of breast cancer is extremely rare. Only three papers with the description of five cases have been published in the current literature to our knowledge. Herein, we describe two additional cases of annular erythema as a cutaneous sign of recurrent ductal breast carcinoma; both were misdiagnosed as erythema chronicum migrans.

Dysplastic Lipoma: A Distinctive Atypical Lipomatous Neoplasm With Anisocytosis, Focal Nuclear Atypia, p53 Overexpression, and a Lack of MDM2 Gene Amplification by FISH; A Report of 66 Cases Demonstrating Occasional Multifocality and a Rare Association With Retinoblastoma.

In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat necrosis, and patchy, often mild, adipocytic nuclear atypia. Because of the focal atypia, consultative cases have most often been received with concern for a diagnosis of atypical lipomatous tumor. Similar tumors have been described in small series under the designations "subcutaneous minimally atypical lipomatous tumors" and "anisometric cell lipoma." Sixty-six cases of this tumor type were collected and reviewed. Immunohistochemistry for p53, MDM2, CDK4, Retinoblastoma 1 (RB1) protein, CD34, S100, and CD163 was performed. Cases were tested for MDM2 gene amplification and RB1 gene deletion with fluorescence in situ hybridization (FISH) and for TP53 mutations by Sanger sequencing. Next-generation sequencing analysis using a panel of 271 cancer-related genes, including TP53, RB1, and MDM2, was also carried out. Our patient cohort included 57 male patients, 8 female patients, and 1 patient of unstated sex, who ranged in age from 22 to 87 years (mean: 51.2 y). All tumors were subcutaneous, with most examples occurring on the upper back, shoulders, or posterior neck (86.4%). Ten patients had multiple (2 to 5) lipomatous tumors, and the histology was confirmed to be similar in the different sites in 4 of them, including 1 patient who had a retinoblastoma diagnosed at age 1. The tumors were generally well circumscribed. At low magnification, there was notable adipocytic size variation with single-cell fat necrosis in the background associated with reactive histiocytes. Adipocytic nuclear atypia was typically patchy and characterized by chromatin coarsening, nuclear enlargement, and focal binucleation or multinucleation. Focal Lochkern change was frequent. In most instances, the degree of atypia was judged to be mild, but in 3 instances, it was more pronounced. Spindle cells were sparse or absent, and when present, cytologically bland. Thick ropy collagen bundles were absent. In all cases, p53 immunoexpression was noted (range: 2% to 20% of adipocytic nuclei), characteristically highlighting the most atypical cells. Twenty of 50 cases had MDM2 immunoreactivity, usually in <1% of the neoplastic cells, but in 4 cases, up to 10% of the cells were positive. Of 32 cases tested, 22 showed a near total loss of RB1 immunoexpression, and the remainder showed partial loss. Three of 13 cases showed RB1 gene deletion in >45% of the cells by FISH (our threshold value for reporting a positive result) with an additional 3 cases being very close to the required cutoff value. MDM2 gene amplification was absent in all 60 cases tested, including those with the greatest MDM2 immunoexpression and most pronounced atypia. All 5 tested cases showed no TP53 mutation with Sanger sequencing. Because of material quality issues, next-generation sequencing analysis could be performed in only 3 cases, and this did not reveal any recurrent mutations. All tumors were managed by simple local excision. Follow-up was available for 47 patients (range: 1 to 192 mo; mean: 27 mo) and revealed 2 local recurrences and no metastases. Dysplastic lipoma is a distinctive atypical fatty tumor variant that has p53 overexpression and RB1 gene abnormalities and lacks MDM2 gene amplification by FISH. These tumors have a strong male predominance and a notable tendency to involve the subcutaneous tissue of the shoulders, upper back and posterior neck. Multifocality is frequent (18.9% of patients with follow-up information), and there is a rare association with retinoblastoma. This tumor warrants separation from ordinary lipoma with fat necrosis, fat-rich spindle cell lipoma and the conventional form of atypical lipomatous tumor that features MDM2 gene amplification.

EWSR1-SMAD3-rearranged Fibroblastic Tumor: An Emerging Entity in an Increasingly More Complex Group of Fibroblastic/Myofibroblastic Neoplasms.

Three cases of superficial acral fibroblastic spindle cell neoplasms with EWSR1-SMAD3 fusion have been recently reported. Their differential diagnosis is broad, primarily comprising rare tumors from the fibroblastic/myofibroblastic category. The aim of this report is to present 4 new cases of this entity and to discuss the appropriate differential diagnosis. Also, as the ERG antibody seems to be a characteristic marker for these tumors, we analyzed ERG immunostaining characteristics in potential mimics of this entity. All cases in our cohort occurred in women aged 5 to 68 years (mean, 36.5 y). Two were located on the hand, 1 on foot, and the last case arose on the calf. The tumor size ranged from 1 to 1.5 cm in the greatest dimension, with a mean size of 1.2 cm. Except for one recent case, follow-up was available, ranging from 7 to 18 years (mean, 11.7 y), with a recurrence noted in 1 case after 10 years. All tumors were subcutaneous and showed 2 main components. One consisted of bland, spindled cells with elongated nuclei which were round when observed on the cross-section. These cells mostly grew in relatively hypercellular, well-organized, and intersecting fascicles. The second component was prominently hyalinized and paucicellular, but lacked calcifications. Both components showed either a distinct zonation pattern, or they were randomly intermingled with each other. In all 3 analyzable tumors, next-generation sequencing showed EWSR1-SMAD3 gene fusion in each case. By fluorescence in situ hybridization, one tested case also revealed unbalanced rearrangement of the EWSR1 gene. All 4 cases showed strong, diffuse nuclear expression of ERG, whereas none of the mimics stained with this antibody except for weak to moderate staining in calcifying aponeurotic fibromas (9/10 cases). Two tumors showed focal weak to moderate expression of SAT-B2. The 4 herein presented cases further broaden the clinicopathologic spectrum of tumors with EWSR1-SMAD3 gene fusion. They also confirm that they represent a novel entity for which we propose the name EWSR1-SMAD3-rearranged fibroblastic Tumor. Our study also proves that in the context of fibroblastic/myofibroblastic tumors, ERG immunohistochemistry is a relatively specific marker for these neoplasms.

Bee-derived antibacterial peptide, defensin-1, promotes wound re-epithelialisation in vitro and in vivo.

Royal jelly (RJ) has successfully been used as a remedy in wound healing. RJ has multiple effects, including antibacterial, anti-inflammatory and immunomodulatory activities, in various cell types. However, no component(s) (other than antibacterial) have been identified in RJ-accelerated wound healing. In this study, we demonstrate that keratinocytes are responsible for the elevated production of matrix metalloproteinase-9 (MMP-9) after incubation with a water extract of RJ. Furthermore, the keratinocyte migration and wound closure rates were significantly increased in the presence of RJ extract. MMP-9 production was reduced significantly following proteinase K treatment but remained stable after heat treatment, indicating that active component(s) have a proteinous character. To identify the component responsible for inducing MMP-9 production, RJ extract was fractionated using C18 RP-HPLC. In fractions exhibiting stimulatory activity, we immunochemically detected the bee-derived antibacterial peptide, defensin-1. Defensin-1 was cloned, and recombinant peptide was produced in a baculoviral expression system. Defensin-1 stimulated MMP-9 secretion from keratinocytes and increased keratinocyte migration and wound closure in vitro. In addition, defensin-1 promoted re-epithelisation and wound closure in uninfected excision wounds. These data indisputably demonstrate that defensin-1, a regular but concentration variable factor found in honey and RJ, contributes to cutaneous wound closure by enhancing keratinocyte migration and MMP-9 secretion.

Detection of Borrelia burgdorferi sensu stricto and Borrelia garinii DNAs in patient with Hyperkeratosis lenticularis perstans (Flegel disease).

Determination of the causative agent of erythema-like skin lesions in case of nonspecific superficial perivascular dermatitis was supported by histological examination and led to the latter diagnosis of Hyperkeratosis lenticularis perstans (Flegel disease) in patient. The presence of antibodies against Borrelia burgdorferi in patient serum was confirmed by a routine ELISA method and verified by Western blot technique. Skin biopsy and blood specimens were analyzed by PCR and multilocus sequence analysis (MLSA). Western blot method revealed IgG antibody response against two specific antigens, 17 and 83 kDa proteins. The recombinant test detected IgG antibody response against p100 and p41 antigens. The sequence analysis of amplicons from the selected genomic loci obtained from skin biopsy and serum samples revealed the presence of two species from B. burgdorferi sensu lato complex as a co-infection in this patient-B. burgdorferi sensu stricto (s.s.) and Borrelia garinii.

[Unusual lung finding of massive alveolar filling with foamy macrophages in congenital epidermolysis bullosa after amnion fluid aspiration in 15-day-old newborn without any clinical signs of respiratory impairment]. / Neobvyklý plúcny nález masívneho vyplnenia alveolov penovitými makrofágmi pri kongenitálnej epidermolysis bullosa po aspirácii súcastí plodovej vody u novorodenca prezívajúceho 15 dní bez akýchkolvek príznakov poskodenia dýchacích funkcií.

Epidermolysis bullosa represents a group of mechanobullous diseases which are most commonly genetically determined. We describe the case of a 15-day-old female newborn with congenital epidermolysis bullosa which was inflicted on aproximately 1/3 of her skin surface, who died because of incorrigible sepsis with multiorgan failure. The main topic of our report is a description of an unusual pulmonary finding of massive alveolar filling with foamy macrophages after amnion fluid aspiration, which contained a excessive amount of desquamated epidermal cells. Introduced case shows outstanding discrepancy of negative clinical finding on one side and massive histopathological finding on the other.

CD30+ clonal T-cell lymphoid proliferation of the skin in a patient with hypereosinophilic syndrome.

We report a hitherto undescribed unusual CD30+ clonal T-cell proliferation in a 46-year-old man with the lymphocytic variant of hypereosinophilic syndrome with a 17-year history of pruritus, generalized persistent papulonodular skin lesions and peripheral blood hypereosinophilia. A skin biopsy showed an eosinophil-rich infiltrate with small to medium-sized CD30+ lymphocytes and Churg-Strauss granulomas. Peripheral blood flow cytometry revealed an aberrant T-cell clone which, molecular genetically, was identical to the T-cell clone detected in the skin. No genetic aberrations of platelet-derived growth factor receptor alpha (PDGFRA), FIP1L1-PDGFRA, PDGFRB or FGFR1 were found. The skin lesions showed transient response to systemic and topical corticosteroids. The skin lesions represent cutaneous involvement by clonal T-cells in hypereosinophilic syndrome and differ from known cutaneous CD30+ lymphoproliferative disorders.

A case of linear porokeratosis treated with photodynamic therapy with confocal microscopy surveillance.

Linear porokeratosis (LP) is a rare clinical porokeratosis variant, which typically presents at birth, but can also develop in adulthood. Differential diagnosis includes linear lichen planus, lichen striatus, linear verrucous epidermal nevus, incontinentia pigmenti and linear Darier's disease. An LP lesion has an increased risk of transformation into a squamous cell carcinoma or basal cell carcinoma. The treatment of LP is contradictory and disappointing in general. We present a case of a 16-year-old girl with multiple reddish-brown macules and depressions on the medial aspect of her right arm, localized from the palmar joint up to shoulder region in a linear pattern. We performed confocal microscopy (CLSM) of multiple lesions and a punch biopsy after receiving informed consent to confirm the diagnosis. After diagnosis confirmation, we performed Photodynamic therapy (PDT). Methyl aminolevulinate cream in a 160 mg/g concentration (Metvix crm) was applied under occlusion on the previously cleaned surface of every single lesion for 3 hours. The lesions were subsequently illuminated with a dose of 37 J/cm(2) (Aktilite, PhotoCure ASA, Norway). Two months after the first PDT treatment, the patient came for a third PDT session. Treatment follow-up was performed 6 months after the initial PDT session. A CLSM image proved an increase in the width of the stratum spinosum to 42-48 µm, mild post-inflammatory changes were also present. Cosmetic and clinical response up to date at the time of last follow-up (1 year) was satisfactory. No progression was observed.

A novel germline mutation in the CYLD gene in a Slovak patient with Brooke-Spiegler syndrome.

The authors report a 64-year-old female with Brooke-Spiegler syndrome who presented with multiple cutaneous nodules and tumors mostly involving the scalp. Histopathological examination of one of the lesions located in a periauricular area revealed a typical cylindroma. In some neoplastic nodules ductal differentiation and occasional bilayered glands composed of the dark abluminal basal/myoepithelial cells and luminal mucinous cells might be recognized. Apocrine secretion was focally noted. Molecular biologic study of the CYLD gene performed from the peripheral blood identified a novel splice site c.2041+1 G>T mutation. This new germline mutation in the CYLD gene of a Slovak patient with Brooke-Spiegler syndrome extends the catalogue of known CYLD germline mutations in this condition.

Primary adenomyoepithelioma of the sellar region: a case report.

Small nests of an ectopic salivary gland tissue are clinically insignificant and they are an incidental finding at microscopic examination in various organs at autopsy. Intracranially, they are suggested to be the origin of extremely rare sellar tumors that bear a marked resemblance to tumors of the salivary gland. We report a case of 38-year-old man who presented with a sellar mass and partial visual loss. The tumor was surgically removed and microscopic examination showed a lesion consistent with adenomyoepithelioma as known in salivary gland pathology. After the surgery, the patient was administered substitution treatment for pan-hypopituitarism and diabetes insipidus. The neoplasm recurred 14 years after surgery in the same location. Transfrontal decompressive operation was followed by a transnasal procedure during which gross total removal of the tumor was achieved. The recurrent tumor displayed an identical morphology to the initial neoplasm; the only difference was an increase in the proliferative activity of the neoplastic cells in the recurrent growth. Six months after the surgery for the recurrent neoplasm, there are no clinical and radiological signs of tumor progression.