Clinicopathological and Immunohistochemical Study of 14 Cases of Morbihan Disease: An Insight Into Its Pathogenesis.

INTRODUCTION: Morbihan disease (MORD) is rare with only 45 clear-cut cases previously reported. Histopathologic findings are supposed to be nonspecific. We report 14 patients and review the previous cases. OBJECTIVES: To characterize the clinicopathologic findings, outcomes, and immunophenotype of MORD. MATERIAL AND METHODS: Inclusion criteria were a clinical picture of persistent, nonpitting edema affecting the mid and or upper third of the face and histopathological findings fitting previous reports and exclusion of other entities. RESULTS: The majority of our patients were males (71.5%) with a male/female ratio of 10/4. The mean age when diagnosed was 58.8 years. Eyelids and forehead were the most frequently involved areas. Two of the patients presented previous rosacea. Most constant histopathological findings were lymphatic vessel dilatations in the upper dermis and the presence of mast cells (7.5 in 10 high-power field as a mean). Mild edema was also present in most of the cases. Granulomas were found in 7 of the cases, and immunostaining with CD68 and CD14 only revealed an additional case. CONCLUSIONS: MORD occurs more in middle-aged males, not associated with rosacea and mostly affects eyelids and forehead. Granulomas are not mandatory for the diagnosis. Histopathology of MORD fits within the spectrum of localized lymphedema.

A primary cutaneous vascular neoplasm with histologic features of anastomosing hemangioma.

Anastomosing hemangioma (AH) is a relatively novel variant of benign vascular tumors originally described in the genitourinary tract. Although AH was subsequently documented in various anatomic locations, a primary AH of the skin has not been reported in the literature. The current case report documents a vascular lesion with histologic features reminiscent of an AH. A 41-year-old female patient underwent an excision of a painful nodule on the leg. Histologic examination showed a well-circumscribed vascular lesion composed of anastomosing sinusoidal capillary-sized vessels, several intravascular fibrin thrombi, rare intraluminal nucleated red blood cells, and focal intracytoplasmic hyaline globules. As AH was hitherto only documented in extracutaneous sites, most dermatopathologists are probably not familiar with this variant of hemangioma. The current case report details the morphologic features of a potential example of a primary cutaneous AH to increase the awareness of this distinctive hemangioma variant among dermatopathologists. Larger studies of vascular lesions with similar histologic features and immunohistochemical profiles are warranted to investigate the potential existence of primary AH in the skin.

Detection of Beta-Human Papillomavirus in a Child With Polyomavirus-Associated Trichodysplasia Spinulosa.

Viral associated trichodysplasia spinulosa (VATS) is a rare cutaneous eruption characterized by folliculocentric papules, keratin spicules, and alopecia associated with trichodysplasia spinulosa-associated polyomavirus (TSPyV) infection. We report a case of a 6-year-old male child who presented with a generalized papular eruption during chemotherapy for acute lymphoblastic leukemia. The papules were tested for human papillomavirus (HPV) DNA by nested polymerase chain reaction (PCR) and TSPyV using PCR and gene sequencing studies. The lesions were positive for TSPyV by PCR combined with sequencing and showed high copy number with real-time PCR, and beta-papillomavirus was identified by PCR and sequencing. Immunohistochemistry revealed inner root sheath keratinocytes expressing nuclear HPV L1 capsid antigen. To our knowledge, this is the first case of concomitant productive HPV and TSPyV infection in a VATS-affected patient. The presence of HPV may be coincidental, however, further studies are needed to establish whether specific HPV genotypes influence the development of abnormal inner root sheath trichohyalin granules found in VATS.

Brief Report: HPV-17 Infection in Darier Disease With Acrokeratosis Verrucosis of Hopf.

The co-existence of Darier disease (DD) and acrokeratosis verruciformis of Hopf (AKV) has been noted for decades and the relationship between the 2 entities remains controversial. Although, it has been shown that both diseases are associated with mutations in ATPA2 gene, it is yet to be determined if they are the same disease, or separate but allelic, or interlinked in some other fashion. Herein, the authors report the case of a 13-year-old girl presenting with shiny flat-topped verruca plana-like papules, on the dorsal hands and feet and red-brown crusted papules on her forehead and along the sides of her neck. Histological evaluation of a wart-like lesion shows features of AKV, a verruca plana-like histopathology and focal acantholytic dyskeratosis. Forehead biopsy also demonstrated focal acantholytic dyskeratosis supporting the diagnosis of DD. Polymerase chain reaction for human papillomavirus (HPV) DNA detected HPV-17, a human betapapillomavirus in the verruca plana-like papule. Cytoplasmic expression of the L1 capsid expression was seen in areas of hypergranulosis. The presence of productive betaPV infection in the setting of DD and AKV suggests a susceptibility to HPV infection.

Chronic Localized Fibrosing Leukocytoclastic Vasculitis Associated With Lymphedema, Intralymphatic and Intravascular Lymphocytosis, and Chronic Myelogenous Leukemia: A Case Report of Unilateral Erythema Elevatum Diutinum.

One of the pathogenic causes of cutaneous inflammatory pseudotumors is chronic localized fibrosing leukocytoclastic vasculitis (CLFLCV), a vasculitic reaction pattern seen in granuloma faciale (GF), a localized vasculitis, and erythema elevatum diutinum (EED), a generalized vasculitis. Patients with myelodysplastic syndromes (MDSs) are at risk for a diverse spectrum of cutaneous neutrophilic dermatoses such as EED. Herein, we report a 74-year-old man who presented with a large ulcerative, fungating tumor affecting the right flexor ankle caused by CLFLCV. During his workup and management, MDS and Philadelphia chromosome-negative chronic myeloid leukemia was diagnosed. Surgical excision of the inflammatory mass promptly triggered tumor recurrence, whereas antineutrophil therapy (dapsone coupled with hydroxyurea, and prednisone) lead to tumor regression. Histopathologic examination revealed an eosinophilic-rich small-vessel neutrophilic vasculitis associated with storiform and angiocentric fibrosis (GF-like). In the regions of fibrosis, dilated lymphatic and vascular spaces were numerous, some of which were congested with small CD3-positive lymphocytes (intralymphatic and intravascular lymphocytosis). These findings indicate coexisting localized lymphedema. By direct immunofluorescence, IgM and C4d vessel deposits were detected. The pathogenesis of the fibrotic nodules and plaques of CLFLCV is suspected to be due to recurring bouts of immune-complex vasculitis, creating a cycle of vessel damage followed by reparative granulation tissue. Poor lymphatic drainage may be the underlying factor initiating and maintaining recurrent, localized episodes of immune-complex vasculitis and progressive fibrosis. Although his tumor histopathology resembled GF-eosinophilic rich CLFLCV-the clinical context points to a solitary and paraneoplastic case of EED.

Cutaneous polyarteritis nodosa localized to a region of lymphedema secondary to Streptococcus viridans cellulitis and multiple surgeries.

Cutaneous polyarteritis nodosa (CPAN) is a chronic, indolent, single organ arteritis that generally presents with lower extremity nodules and/or livedo racemosa, accompanied by malaise and arthralgias. CPAN is often triggered by infection, commonly Group A streptococcal species, and is considered an autoimmune reaction. Scarring from surgery and obliterative lymphangiitis from bacterial cellulitis are the causes of lymphedema. Lymphedematous skin is predisposed to autoimmune disorders. Herein we report a 53-year-old woman who developed CPAN restricted to a localized area of the right upper arm-shoulder that had undergone multiple surgeries, complicated by episodes of Streptococcus viridans cellulitis. Clinically, a 15 cm diameter plaque exhibited violaceous, reticulate margins, subtle papules and nodules and central livedo racemosa. Biopsy showed numerous foci of arteritis in active, subacute and reparative stages. In addition, a broad zone of fibrosis replaced the deep dermis-subcutis zone and harbored numerous dilated lymphatic vessels scar lymphedema. Treatment consisted of high potency topical corticosteroids under occlusion; remission after 3 months therapy and follow-up. CPAN primarily affects the lower legs, a region of frequently affected by phlebolymphedema. This report of CPAN localized to an area of scar lymphedema underscores the importance of lymphatic function in the pathogenesis of CPAN.

Compact characterization of liquid absorption and emission spectra using linear variable filters integrated with a CMOS imaging camera.

A compact analysis platform for detecting liquid absorption and emission spectra using a set of optical linear variable filters atop a CMOS image sensor is presented. The working spectral range of the analysis platform can be extended without a reduction in spectral resolution by utilizing multiple linear variable filters with different wavelength ranges on the same CMOS sensor. With optical setup reconfiguration, its capability to measure both absorption and fluorescence emission is demonstrated. Quantitative detection of fluorescence emission down to 0.28 nM for quantum dot dispersions and 32 ng/mL for near-infrared dyes has been demonstrated on a single platform over a wide spectral range, as well as an absorption-based water quality test, showing the versatility of the system across liquid solutions for different emission and absorption bands. Comparison with a commercially available portable spectrometer and an optical spectrum analyzer shows our system has an improved signal-to-noise ratio and acceptable spectral resolution for discrimination of emission spectra, and characterization of colored liquid's absorption characteristics generated by common biomolecular assays. This simple, compact, and versatile analysis platform demonstrates a path towards an integrated optical device that can be utilized for a wide variety of applications in point-of-use testing and point-of-care diagnostics.

Lymphocytic Arteritis in Epstein-Barr Virus Vulvar Ulceration (Lipschütz Disease): A Report of 7 Cases.

Epstein-Barr virus (EBV) infection can rarely present as painful genital ulcers, mostly in young female adolescents. Typically diagnosed by clinical findings, EBV vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all presented with 1 or more painful, punched-out vulvar ulcers. Only patients with acute EBV infection showed other clinical findings: fever and/or atypical lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue, dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis). Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a submucosal scar was found in the eighth specimen. Other histopathologies included venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense angiocentric CD3 CD4 T-cell lymphocyte-predominant infiltrates were found, regionally or diffusely. In 2 specimens, neutrophils compromised half of the infiltrate. Minor components of CD8, CD20, and CD30 lymphocytes, CD123 plasmacytoid monocytes, CD68 macrophages, and plasma cells were present. Small-vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early EBV mRNA (EBER) identified rare solitary or scattered clustered positive lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one EBER positive biopsy. EBV infection has been documented in muscular vessel vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of localized lymphocytic arteritis.

Skin tumors with matrical differentiation: lessons from hair keratins, beta-catenin and PHLDA-1 expression.

BACKGROUND: Pilomatricomas are tumors that emulate the differentiation of matrix cells of the hair follicle, showing cortical differentiation, with sequential expression of K35 and K31 keratins. Beta-catenin gene is frequently mutated in pilomatricoma, leading to beta-catenin nuclear accumulation, and to downstream expression of LEF1. Skin matrical tumors other than pilomatricoma are very rare, and comprise purely matrical tumors and focally matrical tumors. We aimed at studying cortical differentiation, beta-catenin pathway and expression of the follicular stem-cell marker PHLDA1 in a series of matrical tumors other than pilomatricoma. METHODS: In 36 prospectively collected tumors, K31, K35, CK17, LEF1, HOXC13, beta-catenin and PHLDA1 expressions were evaluated. Five pilomatricomas were used as controls. RESULTS: In 18 purely matrical tumors (11 matrical carcinomas, 4 melanocytic matricomas, 3 matricomas) and 18 focally matrical tumors (11 basal cell carcinomas, 3 trichoepithelioma/trichoblastomas, 4 others), sequential K35, HOXC13 and K31 expressions were found, indicating cortical differentiation. Germinative matrix cells were always CK17-, and showed nuclear beta-catenin accumulation, with LEF1 and PHLDA1 expressions. CONCLUSIONS: Nuclear beta-catenin and LEF1 expression was highly conserved in matrical tumors, and suggested a common tumorigenesis driven by Wnt pathway activation. PHLDA1 was consistently expressed in matrical tumors and in areas of matrical differentiation.

The spectrum of grossly visible pigmented lesions in the uterine cervix: a prospective study.

Pigmented lesions of the uterine cervix (UC) have not been systematically studied in the literature. Over an 18-mo period, we prospectively investigated the histologic spectrum of all macroscopically visible pigmented lesions of the UC. The incidence of pigmented UC was 1.6% (33/2118). Histologic examination revealed 32 cases (97%) with a histologic correlate, of which 26 lesions were of melanocytic nature including 25 blue nevi (BNs) (81%) and 1 melanotic macule (3%). The nonmelanocytic lesions included 1 case of focal granulomatous vasculitis (3%), 2 biopsy site-associated reactive changes with hemosiderin-laden macrophages (6.4%), 1 case of hemorrhagic Nabothian cyst (3%), 1 hemangioma (3%), and 1 case of multinucleated giant cell reaction to dark black carbon-like material (3%). Women with UC BN (1.2% incidence) were mostly whites (13/25, 52%) with a mean age of 47.4 yr (range, 31-64 yr). The number and size of BN per UC, all located in the endocervix, varied between 1 to 3 and 0.1 to 2 cm (mean, 0.68 cm). UC BN exhibited 3 distinct morphologic patterns: (1) stromal melanocytic focus composed of fine spindle cells (9/25, 36%); (2) mixed pattern with fine spindle, plump spindle, and epithelioid cells (15/25, 60%); and (3) nevoid stage with epithelioid cells (1/25, 4%). In contrast, cervical melanotic macule was located in the squamous epithelium of the ectocervix and characterized by hyperpigmentation of the basal keratinocytes admixed with scattered slightly enlarged melanocytes. In conclusion, pigmented lesions of the UC are not as uncommon as reported and mostly benign in nature. Several cases may require deeper levels for their detection and to exclude the rare phenomenon of UC melanoma.

Recurrent hemorrhagic ascites: a rare presentation of endometriosis.

BACKGROUND: Endometriosis is rarely a cause of recurrent hemorrhagic ascites. This report draws attention to this uncommon condition, which could present a diagnostic dilemma. CASE: A young African-American woman who had experienced recurrent hemorrhagic ascites for more than 2 years underwent laparotomy and was found to have extensive pelvic endometriosis. After a hysterectomy and bilateral salpingo-oophorectomy, her ascites resolved. CONCLUSION: Endometriosis should be considered in the differential diagnosis of recurrent hemorrhagic ascites in premenopausal women. The diagnosis always requires operative assessment and histologic confirmation.

Frequent loss of pRb2/p130 in human ovarian carcinoma.

PURPOSE: RB2/p130, a member of the retinoblastoma gene family, maps to human chromosome 16q12.2, a region in which deletions have been found in several human neoplasms including breast, prostatic, and ovarian carcinoma. We sought to evaluate pRb2/p130 protein expression and function in ovarian carcinoma. EXPERIMENTAL DESIGN: pRb2/p130 expression was detected by immunohistochemical and Western blot analyses in 45 primary ovarian carcinoma samples. RESULTS: Immunohistochemical analysis revealed loss or decrease of pRb2/p130 expression in 18 cases (40%). pRb2/p130 expression was mostly nuclear and inversely correlated to the tumor grade (P < 0.05). Western blot analysis correlated with immunohistochemical expression. Reverse transcription-PCR followed by Southern blot analysis was performed on a representative set of 20 ovarian carcinomas. RB2/p130 mRNA levels were consistent with protein expression. We found a significant increase in the percentage of G(1)-phase-arrested cells in CAOV3 and A2780 ovarian carcinoma cell lines after transduction with an adenovirus carrying the RB2/p130 gene (Ad-CMV-RB2/p130). CONCLUSIONS: These data indicate that loss or decrease of pRb2/p130 expression is a frequent event in ovarian carcinoma and is regulated mostly at the transcriptional level. Moreover, pRb2/p130 overexpression is able to arrest cell growth in ovarian carcinoma cells, suggesting the putative role of pRb2/p130 as a tumor suppressor in this malignancy.

Metastatic cervical carcinoma with ectopic calcitonin production presenting as a thyroid mass.

OBJECTIVE: To describe a case of cervical carcinoma metastatic to the thyroid in association with ectopic production of calcitonin. METHODS: We present the medical history, clinical findings, and laboratory results in a 38-year-old woman with a neck mass, and we discuss the frequency of metastatic involvement of the thyroid. RESULTS: A 38-year-old woman was referred for evaluation of an enlarging neck mass. She had undergone radical hysterectomy and irradiation for invasive cervical carcinoma 1 year earlier. Laboratory investigation showed only mild anemia, high plasma bicarbonate concentration, increased alkaline phosphatase, and mild hypoalbuminemia. Computed tomography of the abdomen and pelvis disclosed multiple lesions in the liver. Fine-needle aspiration biopsy of the thyroid mass revealed a poorly differentiated carcinoma, which stained negative for thyroglobulin but positive for several neuroendocrine tumor markers. Measurement of serum calcitonin showed a dramatically increased level (5,000 pg/mL). The same histologic and immunochemical profile was found in a liver biopsy specimen and in the original cervical tumor. Metastatic neuroendocrine cervical carcinoma was diagnosed, and the patient died 6 months later despite four cycles of chemotherapy. CONCLUSION: To the best of our knowledge, this is the first case report of a neuroendocrine cervical carcinoma manifesting as a palpable thyroid mass, associated with ectopic production of calcitonin.