A microvenular hemangioma with a rare expression of progesterone receptor immunocreativity and a review of the literature.

Microvenular hemangioma (MVH) is a rare benign vascular tumor with a controversial etiology, but hormone receptor alterations might be involved. We report a case of MVH in a 41-year-old Taiwanese woman who presented with a 1.5 × 1 cm violaceous plaque on left thigh that had appeared 1 year previously. She had taken oral contraceptives for several years and stopped 1 year prior to presentation. Histologically, the tumor was composed of small and compressed venous structures infiltrating in the dermis and subcutis. Immunohistochemically, the tumor cells displayed negative immunoreactivity for human herpesvirus-8 and positive immunoreactivity for smooth muscle actin and progesterone receptor (PR). Taken together with the patient's medical hormone therapy history and the evidence of PR immunoreactivity, our findings support that progesterone may be associated with the tumorigenesis of MVH.

EGFR-driven up-regulation of decoy receptor 3 in keratinocytes contributes to the pathogenesis of psoriasis.

Decoy receptor 3 (DcR3) is a soluble receptor of Fas ligand (FasL), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A) and plays pleiotropic roles in many inflammatory and autoimmune disorders and malignant diseases. In cutaneous biology, DcR3 is expressed in primary human epidermal keratinocytes and is upregulated in skin lesions in psoriasis, which is characterized by chronic inflammation and angiogenesis. However, the regulatory mechanisms of DcR3 over-expression in skin lesions of psoriasis are unknown. Here, we demonstrate that DcR3 can be detected in both dermal blood vessels and epidermal layers of psoriatic skin lesions. Analysis of serum samples showed that DcR3 was elevated, but FasL was downregulated in psoriatic patients compared with normal individuals. Additional cell studies revealed a central role of epidermal growth factor receptor (EGFR) in controlling the basal expression of DcR3 in keratinocytes. Activation of EGFR by epidermal growth factor (EGF) and transforming growth factor (TGF)-α strikingly upregulated DcR3 production. TNF-αenhanced DcR3 expression in both keratinocytes and endothelial cells compared with various inflammatory cytokines involved in psoriasis. Additionally, TNF-α-enhanced DcR3 expression in keratinocytes was inhibited when EGFR was knocked down or EGFR inhibitor was used. The NF-κB pathway was critically involved in the molecular mechanisms underlying the action of EGFR and inflammatory cytokines. Collectively, the novel regulatory mechanisms of DcR3 expression in psoriasis, particularly in keratinocytes and endothelial cells, provides new insight into the pathogenesis of psoriasis and may also contribute to the understanding of other diseases that involve DcR3 overexpression.

Generalized bullous fixed drug eruption is distinct from Stevens-Johnson syndrome/toxic epidermal necrolysis by immunohistopathological features.

BACKGROUND: Generalized bullous fixed drug eruption (GBFDE), a particular form of fixed drug eruption (FDE), is characterized by widespread blisters and erosions and can be confused with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVE: We sought to analyze specific features of GBFDE and differentiate it from SJS/TEN. METHODS: We retrospectively studied patients with GBFDE and SJS/TEN during a period of 10 years. GBFDE was defined as typical FDE lesions with blisters involving at least 10% body surface area on at least 3 of 6 different anatomic sites. Clinical presentations; histopathological features; immunohistochemical patterns of cluster-of-differentiation (CD)3, CD4, CD8, CD56, Fas, Fas ligand, granzyme B, perforin, granulysin, and forkhead box P3 (Foxp3); and serum granulysin levels were compared. RESULTS: Twenty-three cases of GBFDE were collected. Patients with GBFDE had shorter latent periods, less mucosal involvement, more eosinophil infiltration, and dermal melanophages. Lesional infiltrates in GBFDE had more dermal CD4(+) cells including Foxp3(+) regulatory T cells, fewer intraepidermal CD56(+) cells, and fewer intraepidermal granulysin(+) cells. The serum level of granulysin in GBFDE was also significantly lower than in SJS/TEN. LIMITATIONS: The number of cases in this study is small. CONCLUSION: GBFDE is a distinct disease distinguishable from SJS/TEN by particular features such as granulysin, CD56, and Foxp3 expressions.

Endocrine mucin-producing sweat gland carcinoma occurring on extra-facial site: a case report.

Cutaneous endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a very rare low-grade malignant neoplasm analogous to the mammary solid-papillary carcinoma. It frequently expresses neuroendocrine markers and may show mucinous differentiation. Although the nodules are circumscribed, myoepithelial cells cannot be showed in most cases and about half of the cases are associated with invasive mucinous carcinoma. Hence, it has been suggested to be invasive and the precursor lesion of some primary cutaneous mucinous carcinomas. After being recognized as a distinct entity, all cases reported to date occurred either in the periocular region or on the cheek. Two thirds of the patients were female. Herein we present an unusual case of in situ EMPSGC on the chest wall skin of a middle-aged man.

Phenotype-genotype correlations in patients with TGFBI-linked corneal dystrophies in Taiwan.

PURPOSE: To determine the phenotype-genotype correlations in patients with corneal dystrophies associated with human transforming growth factor-ß-induced (TGFBI) mutations at the National Taiwan University Hospital. METHODS: Twenty-five affected patients from 15 families with corneal dystrophies were recruited. They underwent slit-lamp biomicroscopy and visual acuity examinations. Genomic DNA was extracted from their peripheral blood, and the exons amplified from TGFBI were sequenced. RESULTS: Eleven patients from 9 families with granular corneal dystrophy (GCD) presented with a wide spectrum of dot or fleck opacities and shared some similar clinical features. Genetic studies revealed an R124H mutation in 5 families and an R555W mutation in 4 families. A patient with GCD type 2 and an R124H mutation showed a marked increase in opacities in the laser-assisted in situ keratomileusis (LASIK) flap interface. Six patients from 3 families with superficial honeycomb opacities had an R555Q mutation. Of the 4 patients from 3 families with variant lattice line opacities, 3 from 2 families had an R124C mutation, whereas 1 from the third family had an A546D mutation. Spontaneous mutations were detected in 2 families: an R124C mutation in 1 family with lattice corneal dystrophy (LCD) type I and an A546D mutation in the other with atypical LCD. CONCLUSIONS: In most cases, TGFBI-linked corneal dystrophies had good phenotype-genotype correlations; however, some phenotypic variation was present. The most common mutations in Taiwan were R124H in GCD type 2 and R555W in GCD type 1. The R555Q mutation in Thiel-Behnke corneal dystrophy is not as rare in Taiwan as it is in other Asian countries. Sequencing of TGFBI can aid in the precise classification of these corneal dystrophies.

Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection.

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation.

Hepatosplenic actinomycosis in an immunocompetent patient.

Hepatosplenic abscess caused by Actinomyces is rare and often misdiagnosed as malignancy. Herein, we report a case of hepatosplenic actinomycosis in a 37-year-old immunocompetent man with a 2-month clinical history of intermittent fever and upper left abdominal pain. Physical examination revealed a mildly ill-appearing man with a low-grade fever (38°C) and upper left quadrant abdominal tenderness. Abdominal sonographic examination showed the presence of a 6.3 cm × 6.5 cm heterogeneous abscess with a hypoechoic center and honeycomb appearance in an enlarged spleen (8 cm × 5 cm). Computerized tomography of the abdomen revealed a multiloculated splenic lesion, and laparotomy showed multiple hepatic nodules and a splenic abscess. Histopathological examination of the biopsy revealed filamentous branching bacilli and sulfur granules in the hepatosplenic abscess. The patient successfully underwent splenectomy accompanied by intravenous and oral penicillin treatment. Proper and prompt diagnosis of hepatosplenic actinomycosis is important because the therapeutic plan and prognosis of this pathogen are quite different from other microorganisms and malignancies.

Malignant gastrointestinal neuroectodermal tumor in head and neck: two challenging cases with diverse morphology and different considerations for differential diagnosis.

Malignant gastrointestinal neuroectodermal tumor (MGNET) is a sarcoma typically involving the gastrointestinal tract with neuroectodermal differentiation and EWSR1-ATF1/CREB1 fusions. Recently, rare MGNET cases were reported in extragastrointestinal sites. We identified 2 cases of MGNET arising in unprecedented laryngeal and intracranial locations, respectively. Both cases showed spindle and epithelioid tumor cells with amphophilic to clear cytoplasm and occasionally prominent nucleoli, arranged in solid, fascicular, and pseudoalveolar patterns. Case 1 exhibited moderate to marked nuclear atypia and focal intraepithelial component. In contrast, case 2 comprised predominantly low-grade epithelioid cells with extensive pseudopapillary structures. Both tumors showed an S100/SOX10-positive and HMB45/melan-A-negative immunoprofile as well as EWSR1-ATF1 fusion. A chief obstacle in diagnosing case 1 was the histologic and immunophenotypic resemblance to melanoma. The striking pseudopapillary architecture and the intracranial location of case 2 rendered differential diagnoses including meningioma and ependymoma. With the peculiar locations and morphology, these cases posed great diagnostic challenge.

Targeted Next-generation Sequencing Reveals a Wide Morphologic and Immunophenotypic Spectrum of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma.

Primary intestinal T-cell lymphoma (PITL) is highly aggressive and includes celiac disease-related enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), and primary intestinal peripheral T-cell lymphoma, not otherwise specified (ITCL-NOS). MEITL is the most common PITL in Asia, comprising of monomorphic medium-sized cells typically expressing CD8, CD56, and cytotoxic granules. Occasional cases with intermediate features between MEITL and ITCL-NOS are difficult to be classified and warrant further investigation. We collected 54 surgically resected PITLs from Taiwan, with 80% presenting with bowel perforation. The overall outcome was poor with a median survival of 7 months. Based on histopathology (monomorphic vs. pleomorphic) and immunophenotype, we classified these cases into 4 groups: MEITL with typical immunophenotype (n=34), MEITL with atypical immunophenotype (n=5), pleomorphic PITL with MEITL-like immunophenotype (n=6), and ITCL-NOS (n=9). There was no EATL in our cohort. Targeted next-generation sequencing of the first 3 groups showed highly prevalent loss-of-function mutations for SETD2 (85%, 80%, and 83%, respectively) and frequent activating mutations for STAT5B (64%, 60%, and 50%, respectively) and JAK3 (38%, 20%, and 50%, respectively). In contrast, ITCL-NOS cases had less frequent mutations of SETD2 (56%) and STAT5B (11%) and rare JAK3 mutations (11%). Our results suggest that there is a wider morphologic and immunophenotypic spectrum of MEITL as currently defined in the 2017 WHO classification. MEITL with atypical immunophenotype and PITL with MEITL-like immunophenotype shared clinicopathologic and molecular features similar to MEITL but distinct from ITCL-NOS, indicating that such cases may be considered as immunophenotypic or histopathologic variants of MEITL.

Combination antifungal therapy for disseminated fusariosis in immunocompromised patients : a case report and literature review.

Fusarium species are the second leading cause of disseminated mold infections in immunocompromised patients. The high mortality caused by such infections is attributed to the high resistance of Fusarium species to current antifungal agents. We report the first case of disseminated fusariosis after the use of alemtuzumab, an anti-CD52 monoclonal antibody, in a patient who presented with striking cutaneous and oral cavity lesions. Case reports of combination antifungal therapy for disseminated fusariosis in immunocompromised patients were reviewed. Among 19 published cases in the last 10 years plus this patient, the patients in 14 cases (70%) responded positively to combination antifungal therapy. A clinical response was achieved in seven cases before resolution of neutropenia.

Granulomatous slack skin presenting as acquired ichthyosis and muscle masses.

We describe a case of granulomatous slack skin in a 31-year-old woman with an unusual presentation of acquired ichthyosis and muscular masses involving four limbs over 3 years. Vesicles and ulcerative skin nodules first appeared only 3 months prior to diagnosis. The diagnosis was confirmed after sequential biopsies of muscle, skin lesions, and lymph nodes, together with molecular genetic studies. The patient responded poorly to various therapies, including thalidomide, and died of doxorubicin-related cardiomyopathy.

Sweet syndrome with histiocytoid infiltrate and neutropenia: a rare combination.

Histiocytoid Sweet syndrome is a recently described variant of acute febrile neutrophilic dermatosis. The histiocytoid cells are easily misinterpreted as histiocytes, when in fact they are immature myeloid cells. The recognition of myeloperoxidase expression in these cells is important in avoiding confusion with histiocyte-rich dermatoses. Herein, we report a case of histiocytoid Sweet syndrome with neutropenia that had an unusual presentation. The recognition of this rare combination helps expand the spectrum of Sweet syndrome with histiocytoid infiltrate.

Lower gastrointestinal tract tuberculosis: an important but neglected disease.

PURPOSE: Difficulties in early and accurate diagnosis of intestinal tuberculosis lead to frequent misdiagnosis even in endemic areas. This study aimed to investigate clinical and laboratory characteristics of patients with lower gastrointestinal tract tuberculosis (LGITB). MATERIALS AND METHODS: Patients who met the criteria for LGITB in a medical center from 1997 to 2006 were identified and their medical records reviewed. RESULTS: A number of 4,567 patients with culture or histology-proven tuberculosis were identified, and 30 (0.66%) were diagnosed with LGITB. Principal co-morbidities were type II diabetes mellitus (23%) and alcoholism (23%). Twenty-two (73%) had radiographic findings suggestive of pulmonary tuberculosis, which was culture-proven in 13. Mycobacterial cultures from stool or sputum had diagnostic yields of about 50%, comparable to that of histological studies of colonoscopic or surgical biopsies. Multidrug-resistant tuberculosis (MDRTB) was identified in four patients, including two alcoholics. Fourteen underwent surgery; two (14%) received right hemicolectomy under the diagnosis of colon cancer without pre- or intraoperative histological study. The 1-year mortality was 20% but was 50% in patients with MDRTB. CONCLUSIONS: A high rate of alcoholism and diabetes mellitus and a high percentage of MDRTB among alcoholics were observed in our patients with LGITB. The diagnostic yields of stool or sputum mycobacterial culture (50%) were similar to that of intestinal histological study. Pre- or intraoperative histological examination could prevent unnecessarily extensive surgery.

Bacteremia and infective endocarditis caused by a non-daptomycin-susceptible, vancomycin-intermediate, and methicillin-resistant Staphylococcus aureus strain in Taiwan.

We describe the development of nonsusceptibility to daptomycin and vancomycin during treatment for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia associated with infective endocarditis and probable septic thrombophlebitis in a uremic patient. MRSA bacteremia persisted during glycopeptide and subsequent daptomycin treatment but cleared after 5 days' treatment with linezolid and fusidic acid.

Conjunctival resection combined with tenon layer excision and the involvement of mast cells in superior limbic keratoconjunctivitis.

PURPOSE: To evaluate the effectiveness of conjunctival resection combined with Tenon layer excision in treating superior limbic keratoconjunctivitis (SLK) and the involvement of mast cells in SLK. DESIGN: Retrospective, interventional case series. METHODS: Forty eyes of 30 SLK patients who were unresponsive to medical treatment received superior bulbar conjunctival resection, and another 20 patients who underwent cataract and retinal surgery served as a control group. The conjunctiva specimens from study and control patients were examined by hematoxylin and eosin staining and immunohistochemistry using antibodies against mast cell tryptase. RESULTS: In all operated eyes, the clinical symptoms and signs, including irritation and redness and superior bulbar conjunctival hyperemia and superior tarsal conjunctival papillary hypertrophy, subsided significantly three months after the operation. Only three eyes had recurrence from the margin of conjunctival resection, and this was relieved after reoperation. Keratinized conjunctival epithelium, loss of goblet cells, and increased mast cell numbers (P<.05) were found in the SLK group. CONCLUSIONS: Our cases demonstrate that superior bulbar conjunctival resection combined with Tenon layer excision is an effective treatment for SLK. The pathologic findings suggest that mast cells may play a role in the pathogenesis of SLK.

Leukocytoclastic vasculitis with severe cardiac involvement in an infant: a case report.

Severe visceral involvement in leukocytoclastic vasculitis is rare. We report here the case of a 2-month-old male infant with leukocytoclastic vasculitis who initially presented with fever and skin purpura. Endomyocarditis with mitral valve regurgitation, multiple hepatic infarction, and pulmonary hemorrhage developed later. The patient was successfully managed with an aggressive treatment of high frequency oscillation ventilation and extracorporeal membrane oxygenation together with corticosteroid and azathioprine therapy for 3 months. Valvuloplasty was also performed due to irreversible damage of the mitral valve, although long-term oral anticongestive medications were also needed.

Nephrogenic systemic fibrosis associated with gadolinium use.

Nephrogenic systemic fibrosis (NSF) is an idiopathic, progressive, systemic fibrosis that occurs in patients with renal diseases. Recently, gadolinium-containing contrast (Gd-contrast) has become a suspected causal factor for NFS. This report discusses two female patients with end-stage renal disease, aged 70 and 51 years, respectively, who developed histologically proven NSF after exposure to Gd-contrast. Clinically, both patients were characterized by fibrosis and induration of skin and muscle mainly in the limbs with joint contracture. In the first case, NSF developed gradually after undergoing evaluation by Gd-contrast magnetic resonance imaging (MRI) and subsequent surgery for her urothelial carcinoma. In the second patient, NSF developed after undergoing evaluation by Gd-contrast MRI for her right shoulder bursitis with calcification, and the conditions of NSF continued to worsen after the surgical treatment of this right shoulder lesion. Although the role of Gd-contrast in NSF is still not well known, the correlation in our cases strongly suggests that it should be used with cautioned in patients with end-stage renal disease. Both of our patients underwent surgery before or during the development of NSF, indicating that the surgical procedure may be a contributing factor.