bluuebunny/crossref_metadata_2025 huggingface dataset:
Candida albicans forms biofilms on the vaginal mucosa
Authors: Harriott M. M. , Lilly E. A. , Rodriguez T. E. , Fidel P. L. , Noverr M. C.
Published: August 2010

Current understanding of resistance and susceptibility to vulvovaginal candidiasis challenges existing paradigms of host defence against fungal infection. While abiotic biofilm formation has a clearly established role during systemic Candida infections, it is not known whether C. albicans forms biofilms on the vaginal mucosa and the possible role of biofilms in disease. In vivo and ex vivo murine vaginitis models were employed to examine biofilm formation by scanning electron and confocal microscopy. C. albicans strains included 3153A (lab strain), DAY185 (parental control strain), and mutants defective in morphogenesis and/or biofilm formation in vitro (efg1/efg1 and bcr1/bcr1). Both 3153A and DAY815 formed biofilms on the vaginal mucosa in vivo and ex vivo as indicated by high fungal burden and microscopic analysis demonstrating typical biofilm architecture and presence of extracellular matrix (ECM) co-localized with the presence of fungi. In contrast, efg1/efg1 and bcr1/bcr1 mutant strains exhibited weak or no biofilm formation/ECM production in both models compared to wild-type strains and complemented mutants despite comparable colonization levels. These data show for the first time that C. albicans forms biofilms in vivo on vaginal epithelium, and that in vivo biotic biofilm formation requires regulators of biofilm formation (BCR1) and morphogenesis (EFG1).
Long-term impacts of antibiotic exposure on the human intestinal microbiota
Authors: Jernberg Cecilia , Löfmark Sonja , Edlund Charlotta , Jansson Janet K.
Published: August 2010

Although it is known that antibiotics have short-term impacts on the human microbiome, recent evidence demonstrates that the impacts of some antibiotics remain for extended periods of time. In addition, antibiotic-resistant strains can persist in the human host environment in the absence of selective pressure. Both molecular- and cultivation-based approaches have revealed ecological disturbances in the microbiota after antibiotic administration, in particular for specific members of the bacterial community that are susceptible or alternatively resistant to the antibiotic in question. A disturbing consequence of antibiotic treatment has been the long-term persistence of antibiotic resistance genes, for example in the human gut. These data warrant use of prudence in the administration of antibiotics that could aggravate the growing battle with emerging antibiotic-resistant pathogenic strains.
Phenotypic and physiological alterations by heterologous acylhomoserine lactone synthase expression in Pseudomonas putida
Authors: Lee Yunho , Yeom Jinki , Kim Jisun , Jung Jaejoon , Jeon Che Ok , Park Woojun
Published: August 2010

Many bacteria harbour an incomplete quorum-sensing (QS) system, whereby they possess LuxR homologues without the QS acylhomoserine lactone (AHL) synthase, which is encoded by a luxI homologue. An artificial AHL-producing plasmid was constructed using a cviI gene encoding the C6-AHL [N-hexanoyl homoserine lactone (HHL)] synthase from Chromobacterium violaceum, and was introduced successfully into both the wild-type and a ppoR (luxR homologue) mutant of Pseudomonas putida. Our data provide evidence to suggest that the PpoR–HHL complex, but neither PpoR nor HHL alone, could attenuate growth, antibiotic resistance and biofilm formation ability. In contrast, swimming motility, siderophore production and indole degradation were enhanced by PpoR–HHL. The addition of exogenous indole increased biofilm formation and reduced swimming motility. Interestingly, indole proved ineffective in the presence of PpoR–HHL, thereby suggesting that the PpoR–HHL complex masks the effects of indole. Our data were supported by transcriptome analyses, which showed that the presence of the plasmid-encoded AHL synthase altered the expression of many genes on the chromosome in strain KT2440. Our results showed that heterologous luxI expression that occurs via horizontal gene transfer can regulate a broad range of specific target genes, resulting in alterations of the phenotype and physiology of host cells.
A streptococcal effector protein that inhibits Porphyromonas gingivalis biofilm development
Authors: Christopher Aaron B. , Arndt Annette , Cugini Carla , Davey Mary E.
Published: August 2010

Dental plaque formation is a developmental process involving cooperation and competition within a diverse microbial community, approximately 70 % of which is composed of an array of streptococci during the early stages of supragingival plaque formation. In this study, 79 cell-free culture supernatants from a variety of oral streptococci were screened to identify extracellular compounds that inhibit biofilm formation by the oral anaerobePorphyromonas gingivalisstrain 381. The majority of the streptococcal supernatants (61 isolates) resulted in lysis ofP. gingivaliscells, and some (17 isolates) had no effect on cell viability, growth or biofilm formation. One strain, however, produced a supernatant that abolished biofilm formation without affecting growth rate. Analysis of this activity led to the discovery that a 48 kDa protein was responsible for the inhibition. Protein sequence identification and enzyme activity assays identified the effector protein as an arginine deiminase. To identify the mechanism(s) by which this protein inhibits biofilm formation, we began by examining the expression levels of genes encoding fimbrial subunits; surface structures known to be involved in biofilm development. Quantitative RT-PCR analysis revealed that exposure ofP. gingivaliscells to this protein for 1 h resulted in the downregulation of genes encoding proteins that are the major subunits of two distinct types of thin, single-stranded fimbriae (fimAandmfa1). Furthermore, this downregulation occurred in the absence of arginine deiminase enzymic activity. Hence, our data indicate thatP. gingivaliscan sense this extracellular protein, produced by an oral streptococcus (Streptococcus intermedius), and respond by downregulating expression of cell-surface appendages required for attachment and biofilm development.
Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives
Authors: Salonen Anne , de Vos Willem M. , Palva Airi
Published: August 2010

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that has been associated with aberrant microbiota. This review focuses on the recent molecular insights generated by analysing the intestinal microbiota in subjects suffering from IBS. Special emphasis is given to studies that compare and contrast the microbiota of healthy subjects with that of IBS patients classified into different subgroups based on their predominant bowel pattern as defined by the Rome criteria. The current data available from a limited number of patients do not reveal pronounced and reproducible IBS-related deviations of entire phylogenetic or functional microbial groups, but rather support the concept that IBS patients have alterations in the proportions of commensals with interrelated changes in the metabolic output and overall microbial ecology. The lack of apparent similarities in the taxonomy of microbiota in IBS patients may partially arise from the fact that the applied molecular methods, the nature and location of IBS subjects, and the statistical power of the studies have varied considerably. Most recent advances, especially the finding that several uncharacterized phylotypes show non-random segregation between healthy and IBS subjects, indicate the possibility of discovering bacteria specific for IBS. Moreover, tools are being developed for the functional analysis of the relationship between the intestinal microbiota and IBS. These approaches may be instrumental in the evaluation of the ecological dysbiosis hypothesis in the gut ecosystem. Finally, we discuss the future outlook for research avenues and candidate microbial biomarkers that may eventually be used in IBS diagnosis.
The Domino Effect of the Russian Crisis
Authors: Westin Peter
Published: August 2010

The Russian crisis brought a collapse of demand and, as expected, a negative impact on imports to Russia. The effect was felt mainly by the former Soviet republics, which experienced declining terms of trade with Russia. At the same time Russian exports to the CIS (Commonwealth of Independent States) fell, as Russian enterprises became less willing to accept barter deals, which had been common practice in trade with the CIS. The Russian crisis, like the Asian crisis, became contagious. This paper examines the effect of the Russian crisis on the ‘near abroad’, as the ex‐Soviet republics are called in Russia (we do not consider the Baltic republics of Estonia, Latvia and Lithuania, which did not come into the post‐Soviet CIS).
Ownership Structure and Financial Position of Firms in Russia; Empirical Analysis
Authors: Radygin Alexander , Arkhipov Sergey
Published: August 2010

Whereas most research findings are similar as regards appraisal of shifts in enterprise ownership structure, findings of analyses of the ownership—performance relationship are often diametrically opposed or ambiguous. This paper focuses on the most controversial issues or those crucial for determining priorities of government regulation of the corporate sector. An original technique was used to develop a Corporate Conflict Index (CCI) which, based on indirect evidence, summarises the practices of corporate relations in specific companies based on a variety of indirect data, which enabled a relationship between the level of corporate conflicts and financial performance of enterprises to be established. This provides a rational basis for considering measures to protect minority shareholder rights in Russian firms as an important element of the modification of the emerging corporate governance system.
Arrears in a Transition Economy: the Mechanism of Contagion
Authors: Lugovoy Oleg
Published: August 2010

The arrears issue has long been one of the gravest unresolved problems in the Russian economy. With stabilisation of public finances and the onset of economic growth in recent years, the severity of this problem has markedly decreased, but it is too early to claim that it has been completely resolved. This paper analyses macroeconomic aspects of arrears in terms of the hypothesis that arrears are a way of providing hidden subsidies to inefficient production companies. The results of the study point to such negative effects of arrears on the economy as decline in consumption, decrease in demand for real cash balances, encouragement of barter and offsets, veiling of the initial sources of arrears, and distortion of normal market responses to the debtor’s financial problems. The latter is connected to the fact that problems of insolvent firms and entire sectors in the conditions of a system of non‐payments are not confined to specific economic agents but are multiplied and spread throughout the economy, creating financial problems for other firms and sectors as well.

As some sectors of the economy do not accept delays in payment for delivered products, generation of overdue payables in one sector may result in demand constraints and consumption decline in other sectors. In an environment where wage arrears are tolerated, households automatically become a creditor of insolvent sectors, reducing their own consumption.

Offsets do not have any effect on the established system of hidden subsidies, as they decrease accumulated arrears only in the short term. As to barter, it can be viewed as a system of compulsory consumption of goods manufactured by domestic producers.
The Irregular Economy in Systemic Transformation
Authors: Dallago Bruno
Published: August 2010

Although it already existed in Central and Eastern Europe during Soviet times, the irregular economy has boomed in the last dozen years, while undergoing a dramatic change of structure. This boom has sometimes been used to justify the claim that ‘transitional depression’ has been grossly overestimated and, consequently, that growth rates have been underestimated. This paper presents some quantitative estimates in different countries, including Russia. The data show a remarkable difference in the size of the irregular economy in different countries, which calls for explanation. The paper warns against the easy conclusion that the large size of the irregular economy is a synonym for bad official statistics. This warning is then translated into a statistical exercise applied to Hungarian data that offers an evaluation of statistical underestimation and its consequences for growth rates.
The Malassezia sympodialis Allergen Mala s 11 with Sequence Similarity to Manganese Superoxide Dismutase Induces Maturation and Production of Inflammatory Cytokines in Human Dendritic Cells
Authors: Vilhelmsson M. , Ekman G. J. , Zargari A. , Scheynius A.
Published: August 2010

The chronic inflammatory skin disease atopic eczema (AE) affects almost 15% of the population in many countries today. The pathogenesis of AE is not fully understood. A combination of genetic predisposition and environmental factors like microorganisms seems to contribute to the symptoms. The yeast Malassezia sympodialis is part of our normal skin micro flora but can act as an allergen and elicit specific IgE and T‐cell reactivity in patients with AE. Recently, we identified a novel major M. sympodialis allergen, designated Mala s 11 (22.4 kDa), with sequence similarity to the mitochondrial enzyme manganese superoxide dismutase (MnSOD). Interestingly, Mala s 11 has a high degree of homology to human MnSOD. The aim of this study was to examine the effects of recombinant Mala s 11 on antigen‐presenting dendritic cells. Monocyte‐derived dendritic cells (MDDCs) from healthy blood donors were cultured with or without Mala s 11 for different time periods. It was found that the maturation marker CD83 and the costimulatory molecules CD80 and CD86 were upregulated on the MDDCs exposed to Mala s 11 for 24 h, as demonstrated by flow cytometry. Furthermore, coculture of MDDCs with Mala s 11 for 9 h induced an increased production of the inflammatory cytokines IL‐6 (200‐fold), TNF‐α (100‐fold) and IL‐8 (sixfold), as detected by the cytometric bead array (CBA) analysis. Our results suggest that Mala s 11 affects the immune response through DC maturation and production of inflammatory cytokines. The potential cross‐reactivity with human MnSOD needs to be explored and the exact role of Mala s 11 in the pathogenesis of AE assessed in clinical studies involving skin prick and atopy patch tests.
Basal Cell Carcinoma With Matrical Differentiation in a Transplant Patient: A Case Report and Review of the Literature
Authors: Ali F. , Brown A. , Gottwald L. , Thomas J.
Published: August 2010

Background: Shadow cells are characteristic of pilomatricoma, a distinct neoplasm of hair matrix differentiation. Shadow cells within an otherwise classic basal cell carcinoma (BCC) has been referred to as “BCC with matrical differentiation”. We present a case of BCC with matrical differentiation in a transplant patient. To our knowledge, none have been reported arising on the background of immunosuppression. Methods: A 58‐year‐old male cardiac transplant patient had a left hand nodule, which was excised and submitted for routine histologic review. Results: The lesion revealed multiple basaloid tumor masses. In some areas, there was peripheral palisading with stromal retraction artifact, typical of basal cell carcinoma, extending into the deep reticular dermis. The tumor also contained a population of shadow cells, similar to those in pilomatricoma, with basaloid cells in the periphery. Trichohyaline granules were identified in many of the tumor cells. These granules are a hallmark of follicular matrix differentiation. Mitoses were rare. There was no evidence of an infiltrating growth pattern. Conclusion: Basal cell carcinoma with matrical differentiation is a rare subtype of basal cell carcinoma featuring shadow cells, such as those typically seen in pilomatricoma. This tumor has not yet been reported in an immunosuppressed transplant patient.
Metastatic Basal Cell Carcinoma with Neuroendocrine Differentiation or Merkel Cell Carcinoma?
Authors: Andea A. , Mefcalf J. , Satter E. , Adsay V.
Published: August 2010

We present here a case of basal cell carcinoma (BCC) with neuroendocrine features that has transformed into a high‐grade neuroendocrine carcinoma with various morphologic features of Merkel cell carcinoma (MCC). A 54‐year‐old white female was treated for a BCC of the right thigh. Pathologic examination revealed an otherwise classical BCC that demonstrated granular positivity for chromogranin. Six years later the patient developed a right inguinal lymphadenopathy diagnosed as metastatic BCC with squamous changes. The metastatic BCC showed partial peripheral palisading and a trabecular pattern. Two years later the patient underwent a right nephrectomy due to obstruction of the right ureter by metastatic BCC. After another four years the patient came back with extensive involvement of the appendiceal wall and right ovary by a diffusely infiltrating metastatic basaloid and trabecular carcinoma. This time the tumor had many histologic features of MCC and showed strong positivity for chromogranin and also for CK20 and NSE. Electron microscopy revealed neurosecretory granules. This case is an example of a chromogranin positive basal cell carcinoma of the skin, which transformed during multiple recurrences into a high grade neuroendocrine carcinoma with features of Merkel cell tumor, demonstrating the potential for cross differentiation among skin tumors.
Pseudoxanthoma Elasticum (PXE)‐Like Fibers in Patients Without PXE
Authors: Bowen A.R. , Gotting C. , LeBoit P.E. , McCalmont T.H.
Published: August 2010

Pseudoxanthoma elasticum (PXE) is an inherited disorder characterised by progressive calcification of elastic fibers in the skin, eyes and cardiovascular system. Skin lesions show distinctive thickened, fragmented elastic fibers in the reticular dermis. PXE‐like fibers have not been described in patients without PXE. We describe 12 patients without known PXE who demonstrated the incidental finding of small numbers of PXE‐like fibers in association with the following conditions: lipodermatosclerosis, granulomatous dermatitis, lichen sclerosus, morphea profunda, erythema nodosum, septal panniculitis, basal cell carcinoma and fibrosing dermatitis NOS. The biopsies were almost exclusively from the lower extremities of elderly women (mean age 73.8). The affected gene in PXE has been recently described as ABCC6 which codes for a member of the ATP‐binding cassette (ABC) family of proteins. The c.3421C>T mutation has been associated with a high risk of coronary artery disease. We describe a novel assay for this genotype employing real‐time PCR of paraffin embedded skin biopsies. Four patients with PXE‐like fibers were tested in this fashion and did not carry this mutation. Our series demonstrates that light microscopic findings associated with PXE are not specific, as PXE‐like fibers can be observed in patients without clinical or genetic evidence of the disease.
Histologic Evaluation of Mucocutaneous Graft Versus Host Disease in Nonmyeloablative Hematologic Stem Cell Transplants
Authors: Bridge A.T. , Nelson R.P. , Schwartz J.E. , Mirowski G.W. , Billings S.D.
Published: August 2010

Nonmyeloablative hematologic stem cell transplantation (HSCT) is a recent alternative to myeloablative HSCT in the treatment of hematologic malignancies. Graft versus host disease (GVHD) remains as a complication of both types of HSCT. Recently the clinical phenomenon of late‐onset (>100 days) acute GVHD has been described following nonablative HSCT. However, there has been no relevant description of the histologic features of GVHD in this setting. We reviewed clinical and pathologic features of 28 cases of acute and chronic GVHD following nonablative HSCT at out institution between 2000 and 2003. Our results support the observation of late onset acute GVHD in nonablative HSCT. The mean onset of acute GVHD was 109.8 days (range 8–410 days). Furthermore, we identified a subset of patients (8/23) in the acute GVHD group with composite histologic features of both acute and chronic GVHD. This subset was more likely to develop chronic GVHD as compared to patients with only classic acute GVHD, 87.5% versus 25%, respectively (p < 0.01). Composite histologic features could serve a a predictor of an increased risk for the development of chronic GVHD. These patients may potentially benefit from more aggressive treatment than patients with histologic features of solely acute GVHD.
Syringocystadenocarcinoma Papilliferum in Situ: A Case Report and Review of the Literature
Authors: Cai J. , Patel P. , Rasberry R. , Slominski A. , Balazs L.
Published: August 2010

Syringocystadenocarcinoma papilliferum is an exceedingly rare malignant neoplasm of the apocrine glands. There are only about half a dozen cases reported in the literature with one case being an in situ lesion. A 32‐year‐old Nigerian female presented with a 1‐cm, hyperpigmented, slow‐growing verrucous nodule located on her mid‐posterior neck. The lesion had been present since birth. Histopathological examination revealed bilocular cystic cavities with papillary projections lined by double layers of epithelium. The luminal layer was composed of columnar cells with decapitation‐type secretion. The fibrovascular stroma within the papillary projections contains numerous plasma cells with some lymphoid cells. The cystic cavities showed close apposition to the epidermis of the skin with focal, keratinizing squamous epithelium lining that was contiguous to the infundibular epithelium in foci. Necrosis en masse was present within the tumor. There were focal areas of solid aggregates of tumor cells with crowded, pleomorphic, and hyperchromatic nuclei. Many mitoses, some of them atypical, were identified. The tumor was confined within the cystic cavities with no dermal invasion. A diagnosis of syringocystadenocarcinoma papilliferum in situ was made.
Myxofibrosarcoma Initially Presenting as a Pleomorphic Hyalinizing Angiectatic Tumor (PHAT): is PHAT a Precursor or Unique Type of Myxofibrosarcoma?
Authors: Cassarino David S , Mitsuhashi Takako , Barr Ronald J
Published: August 2010

Myxofibrosarcoma (MFS) is a common soft tissue sarcoma of adults. We present an unusual case which initially showed features of a pleomorphic hyalinizing angiectatic tumor (PHAT). The lesion was characterized by abundant plump, eosinophilic cells exhibiting striking nuclear atypia, set in a dense, hyalinized stroma with a prominent, angiectatic vasculature. Rare mitotic figures were identified. These findings were felt to be most consistent with the diagnosis of PHAT. Four months after removal, local recurrence was noted, which demonstrated findings of a high grade MFS, including a cellular proliferation of pleomorphic spindle cells set in a prominent myxoid stroma. Multiple mitoses, including atypical ones, were present. In light of these findings, the original specimen was reexamined and the diagnosis was revised to high‐ grade MFS. MFS, especially low‐grade lesions, may be confused with several benign lesions. Previous cases mimicking PHAT have not been reported. We describe a unique case of high‐grade MFS which initially showed characteristic features of a PHAT, raising the possibility that MFS may occasionally arise in, or have areas that masquerade as, PHAT. It is possible that PHAT, currently considered a benign neoplasm, may actually represent a peculiar form of MFS of low malignant potential.
Melkersson‐Rosenthal Syndrome
Authors: Estrada S. , Trepeta R.
Published: August 2010

A 13 year‐old boy presented with a six‐month history of severe lip swelling. His past medical history was significant for eczema, multiple episodes of urticaria, and two episodes of anaphylaxis. Physical exam revealed severe cheilitis and labial angioedema. The cranial nerves were intact, and there was no evidence of a fissured tongue. A lip biopsy showed noncaseating granulomas throughout the dermis, with extension into the underlying skeletal muscle. Other features included dilated lymphatic channels, some closely approximating the granulomas, and a mild perivascular lymphoplasmacytic infiltrate. The epidermis was acanthotic with parakeratosis and focal acantholysis. Methenamine silver and acid‐fast stains were negative. A laboratory work‐up revealed an increased total eosinophil count, an increased serum IgE level, and a low complement C1q level. All other complement levels were normal. The patient also had an unremarkable chest x‐ray and a normal angiotensin converting enzyme level. This case represents the monosymptomatic form of Melkersson‐Rosenthal syndrome (MRS), also known as cheilitis granulomatosa Meischer. MRS is classically known as a triad of granulomatous cheilitis, facial nerve palsy, and fissured tongue. The onset of granulomatous cheilitis typically precedes the other symptoms, and when present alone, it is known as the monosymptomatic form of MRS.
Post‐Radiation Malignant Fibrous Histiocytoma Following Treatment of Eruptive Squamous Cell Carcinoma In‐Situ in an African American Male
Authors: Fangman W. , Herman C. , Cook J. , Selim A.
Published: August 2010

A 32‐year‐old African American male presented with a five year history of multiple verrucous plaques in a Blaschkoid arrangement on the left leg. Biopsies demonstrated squamous cell carcinoma in‐situ. The patient’s medical history did not reveal any heritable or exposure related risk factors. The patient was treated with radiotherapy. Four years later, he presented with a subcutaneous nodule within a prior site of radiation. MRI showed a 2.0 × 1.2 cm enhancing nodule in the subcutis. On biopsy, an ill‐defined spindle cell proliferation was present in the dermis and subcutis. Marked nuclear pleomorphism and numerous multinucleated cells embedded in a myxoid stroma were noted. Spindle cells stained for CD68. Cytokeratin and S‐100 were negative. A diagnosis of Malignant Fibrous Histiocytoma was rendered. Surgical excision was undertaken. A dominant lesion of MFH was identified, as well as multiple, clinically undetectable foci of early sarcoma. This is an unusual case of multifocal post‐radiation sarcoma in an African American patient with squamous cell carcinoma in‐situ. While sarcoma is a known risk factor following radiotherapy, the course of this patient would suggest caution in applying radiation in similar clinical settings, as well as long‐term clinical follow‐up for early detection and treatment of post‐radiation sarcoma.
Eccrine Poroma: One Tumor, Many Faces
Authors: Forman S.B. , McMullan F.H. , Azmi F.H.
Published: August 2010

Pinkus initially described eccrine poroma as a benign neoplasm of the acrosyringium. The tumor, often consisting of broad anastamosing bands, arises from the epidermis and extends downward into the dermis. However, it may be completely intraepidermal (“hidroacanthoma simplex”), and, at times, appear to be completely dermal (“dermal duct tumor”). The characteristic tumor cell is squamoid, but smaller than the epidermal squamous cell. The cell has a cuboidal appearance with a uniform basophilic nucleus, and intercellular bridges. One can usually observe a sharp line of demarcation between the adjacent epidermis and the tumor cells. The histological sections presented are offered as evidence of the eclectic nature of eccrine poroma. The examples to be discussed include: the intraepidermal variant, the intraepidermal variant with “microcysts, the intraepidermal variant with “macrocysts” the epidermal/classic variant, the dermal variant, the pigmented variant, the irritated variant, the chondroid variant, the syringomatous variant and the focally malignant variant. Each example has the classic features of eccrine poroma and an outstanding individual characteristic. But, all are eccrine poromas. These specimens are from the Medical College of Virginia/Francis H. McMullan collection, representing fifty years of practice, teaching and service.
Completely Regressed Primary Cutaneous Malignant Melanoma with Nodal and/or Visceral Metastases
Authors: High WA , Stewart D , Wilbers CRH , Cockerell CJ , Hoang MP , Fitzpatrick JE
Published: August 2010

Partial regression of primary cutaneous malignant melanoma is not uncommon, and may predict a higher likelihood of metastasis and decreased survival. Complete histologic regression of a primary cutaneous melanoma is a rarer occurrence of uncertain significance, with only 30 cases reported in the literature. Herein, we detail five additional cases of complete histologic regression of a primary cutaneous melanoma, which were discovered upon presentation with metastatic disease. A pigmented lesion, or its remnant, coupled with historical information was strongly suggestive of cutaneous malignant melanoma. However, histologic examination of the lesions in toto using multiple levels, and in some cases immunohistochemical stains, failed to reveal residual melanoma. Our cases are typified by the presence of metastasis of malignant melanoma to regional lymph nodes, with the absence other suspicious lesions or other malignancies. Through these instructive cases, the concept of completely regressed primary cutaneous melanoma is reviewed and the literature critically appraised. When considering a diagnosis of completely regressed primary cutaneous melanoma, it is important that the cases be well‐documented and biopsy‐proven. All patients with a diagnosis of metastatic melanoma with an occult primary lesion require a thorough and complete skin examination and consideration of completely regressed cutaneous melanoma within the differential.
CD44 and Hyaluronate Expression in Follicular Mucinosis
Authors: Kaya Gürkan , Augsburger Eric , Chavaz Pierre , Saurat Jean‐Hilaire
Published: August 2010

CD44 is the cell surface receptor for hyaluronate (HA). We demonstrated that the lack of CD44 expression in murine keratinocytes leads to an abnormal HA accumulation in the dermis, indicating an important role of CD44 in local HA metabolism in mouse skin. We also observed a decrease in the expression of epidermal CD44 in patients of lichen sclerosus et atrophicus which is potentially responsable for the dermal deposition of HA. We also showed that HA accumulation was associated with decreased expression of CD44 in epithelial proliferations in perifollicular solitary cutaneous myxoma. In this study we examined the follicular expression of CD44 and HA in the skin biopsy specimens of seven patients with follicular mucinosis by using CD44‐specific antibodies and biotinylated HA‐binding protein (HABP), respectively. No difference of CD44 expression was observed in the follicular keratinocytes when compared with those of unaffected interfollicular epidermis. The follicular zones of mucin deposition were strongly positive for HA. A weak interkeratinocyte staining pattern for HA was also observed in the interfollicular epidermis. However, HABP staining revealed a stronger reactivity in the follicular keratinocytes surrounding the mucin‐accumulated areas compared to the interfollicular keratinocytes, indicating an active secretion of HA by follicle cells in follicular mucinosis.
Hidradenocarcinoma: Criteria for Malignancy and Hypothesis of an Apoeccrine Origin
Authors: Ko C. , Luo F. , Cochran A. , Binder S.
Published: August 2010

The immunohistochemical profile of hidradenocarcinoma, defined here as the malignant counterpart of hidradenoma, has not been well characterised. We evaluated the staining pattern of six cases of hidradenocarcinoma using antibodies to gross cystic disease fluid protein‐15 (GCDFP‐15), carcino‐embryonic antigen (CEA), epithelial membrane antigen (EMA), S‐100 protein, keratin AE1/3, cytokeratin 5/6, p53, bcl‐1, bcl‐2, and Ki67. All tumours were poorly circumscribed with clefting between tumour and stroma, evidence of poroid cells and cuticular cells, decapitation secretion, and increased mitoses with cords of tumour infiltrating through the adjacent desmoplastic stroma. The tumours stained with antibodies to CEA, S‐100 protein, GCDFP‐15, and EMA in no consistent pattern. All tumours studied stained positively for keratin AE1/3 and cytokeratin 5/6. Ki67 and p53 staining were strongly positive in 5 of 6 tumours. Bcl‐1 and bcl‐2 staining were variable. Our study demonstrates that hidradenocarcinomas may have both apocrine and eccrine features within the same tumour and suggests that it may be most accurate to consider that these tumours originate from apoeccrine structures or stem cells with the capacity for pluripotential differentiation.
Nephrogenic Fibrosing Dermopathy with Osteoid Metaplasia
Authors: Mathur V. , Park H.K. , Finley J.
Published: August 2010

Nephrogenic fibrosing dermopathy is a rare and recently described disease which occurs in patients with a history of renal disease and is often associated with hemodialysis or renal transplants. The usual presentation is multiple indurated plaque lesions resembling scleromyxedema on the extremities and trunk. Nephrogenic fibrosing dermopathy has been described in association with calciphylaxis and metastatic calcification, however, to our knowledge, the occurrence of osteoid metaplasia has not been previously reported. We report a case of nephrogenic fibrosing dermopathy with osteoid metaplasia in a 78‐year‐old female patient with chronic renal failure on dialysis. The patient had a relatively acute onset (a few months) of lesions with irritation and pruritis of the lower extremities. Biopsies showed fibrous thickening of the dermis with islands of osteoid tissue with osteoblastic rimming. Calcification and lamellar bone formation were not seen. An Alcian blue stain demonstrated increased dermal mucin. Elastic stains showed prominent elongated elastic fibers between collagen fibers and within osteoid areas. The differential diagnosis included scleromyxedema and other fibrotic disorders. The pathogenesis of this disorder is unknown. Although rare patients improve with correction of renal abnormalities, currently no effective treatment is available.
The Hair Erector Muscle: Order and Disorder of this Often Forgotten Structure
Authors: Muñoz‐Garcia Liliana , González‐Serva Aldo
Published: August 2010

Hair erector muscle (HEM) is everywhere in dermatopathology but has been less studied than other smooth muscle systems in the skin. HEM disorders are passive and active, the former related to the involvement, as a bystander fascicle, by nearby conditions. The muscle can be permeated by nevus cells, infiltrated or destroyed by keratoacanthoma and other malignancies, encroached by hemangiomas, suffused by erythrocytes in purpura and pyocytes in an abscess, incorporated into scars and entrapped and deformed by a dermatofibroma. Less passively, HEM can participate in follicular processes, insect bites, collagen‐vascular diseases, syphilis, solar elastosis and amyloid. More proper to the muscle yet rarely encountered are myositis (dermatomyositis), poorly understood myopathies (atrophy, vacuolar changes, eosinophilic globules), deposit diseases (glycogenosis) and, even, rare dystrophies (Duchenne/Becker). Finally, other than HEM tumors (leiomyoma, leiomyosarcoma), hamartomatous conditions include disorganized/hypertrophic muscle in blue nevi, hyperplasia in Becker’s nevus, and more substantial muscle mass increase as in smooth muscle hamartoma (including similar changes in mature port‐wine stain) and in the rare congenital midline hamartoma. This presentation outlines orderly features and, mainly, compiles disorders of HEM, few of them a disease on its own but still a supplement to a gamut of many more noticeable entities.
Thrombogenic Vasculopathy and Interstitial to Diffuse Dermal Neutrophilic Inflammation as a Histologic Manifestation of Tick Bite Reaction
Authors: Pajvani Urvi , Basile Orazio , Toback Neil , Zeikus Priya Swamy , Robinson‐Bostom Leslie
Published: August 2010

Ticks are ectoparasites that cause dermatologic disease both directly through physical trauma to the skin, salivary secretions, or remnant body parts, and indirectly through transmission of disease. Lyme disease, Rocky Mountain spotted fever, tularemia, and babesiosis are known tick‐transmitted diseases. The histopathology related to a primary tick bite, similar to other arthropod bites, classically consists of a perivascular infiltrate composed of lymphocytes, neutrophils, histiocytes, plasma cells, and eosinophils in varying amounts. We describe five patients with a novel histologic reaction to embedded tick parts., Each case demonstrates a thrombotic vasculopathy consisting of intraluminal eosinophilic deposits that stain strongly with Periodic acid Schiff stain. The adjacent tissue shows dermal necrosis with surrounding interstitial to diffuse dermal neutrophilic inflammation. We postulate that diffuse dermal nutrophilic infiltrates in association with thrombogenic vasculopathy is an unusual histologic picture of tick bite reactions that may be attributable to remnant tick parts.
Primary Cutaneous Ewing’s Sarcoma/Primitive Neuroectodermal Tumor Mimicking Malignant Eccrine Spiradenoma with 22q12 Translocation by Interphase Fluorescent in Situ Hybridization
Authors: Patel R.M. , Goldblum J.R. , Skacel M. , Downs‐Kelly E. , Tubbs R. , Embi C. , Bergfeld W.F.
Published: August 2010

Cutaneous small blue cell tumors are relatively uncommon neoplasms whose differential includes primary adnexal, neuroendocrine and lymphoproliferative tumors, as well as metastatic lesions. Another entity to be considered in the differential is Ewing’s sarcoma (ES)/primitive neuroectodermal tumor (PNET). We present a 19‐year‐old female who developed a solitary, subcutaneous mass on her back. Histology revealed a poorly differentiated, cellular, nodular neoplasm of small, blue cells containing round to ovoid, vesicular nuclei with indistinct nucleoli and scant eosinophilic cytoplasm. Tumor cells were strongly immunoreactive for antibodies to carcinoembryonic antigen (CEA), Cam 5.2 and CD99. Overall, the lesion resembled an malignant spiradenoma (spiradenocarcinoma). CD99 reactivity prompted analysis with dual‐color interphase FISH for translocations involving (22q12), which was positive, a sensitive marker for ES/PNET. Our case demonstrates that a diagnosis of ES/PNET should be considered in the differential of primary cutaneous blue cell tumors. These lesions are difficult to distinguish from other cutaneous small blue cell tumors due to their rarity and because the diagnosis is often not considered at this site.
Squamous Cell Carcinoma Associated with Epidermal Nevus
Authors: Peralta Soler A. , Becker D.S. , Peters S.B. , McNutt N.S.
Published: August 2010

We present the case of a 27 year‐old female with a linear array of brown keratotic papules with a raised nodule within, located in the right mid upper inner thigh. A biopsy of the nodule showed a superficially invasive squamous cell carcinoma. Subsequent excision of the entire lesion showed an epidermal nevus without residual carcinoma. Squamous cell carcinomas developing within an epidermal nevus constitute an unusual association, mostly occurring in long standing lesions of elderly patients. Other epithelial neoplasms described arising within epidermal nevi include basal cell carcinomas, malignant eccrine tumors and keratoacanthomas. Although our patient did not have an identifiable epidermal nevus syndrome, the presence of a squamous cell carcinoma within an epidermal nevus in a young person suggests increased susceptibility to tumor development. Moreover, chromosomal aberrations have been described in epidermal nevi, including chromosomal breakage and variegated translocation mosaicism. We suggest that the presence of an epidermal nevus should alert the clinician for the potential development of a malignant neoplasm within it, including squamous cell carcinoma, even in the absence of an identifiable hamartoma‐neoplasm syndrome.
Composite Extrarenal Rhabdoid Tumor of the Skin: Cytology, Morphology, Electron Microscopy and Special Stain Findings
Authors: Petitt M. , Doeden K. , Harris A. , Bocklage T.
Published: August 2010

We present the findings of a rare and very aggressive primary skin tumor, composite extrarenal rhabdoid tumor (CERT) with features of rhabdomyosarcoma. Clinical history: A 53‐year‐old woman presented with a 2.5 cm ulcerated nodule on her right medial calf. On exam, she also exhibited inguinal lymphadenopathy. Pathology: Fine needle aspiration of a lymph node and punch biopsy of the skin nodule disclosed an epithelioid cell morphology with rhabdoid cells, solid growth, and a high mitotic rate (>70 figures/10 HPF). Upon wide excision of the tumor, electron microscopy (EM) and special stains were performed. Since the differential diagnosis was broad, a large number of stains were performed: tumor was positive for vimentin, desmin, muscle specific actin, WT‐1, CD56, and CD10, and negative for S‐100, melan A, cytokeratins, EMA, CD34, fast myosin, myoglobin, myogenin, myoD1, smooth muscle actin, and NSE. EM revealed rhabdoid cells with perinuclear globules of intermediate filaments corresponding to the positive desmin stain. Summary: The patient was treated with chemotherapy without regression of presumed lung metastases. The CERT is a rare, aggressive tumor that extraordinarily presents as a primary skin tumor. The differential is broad and nomenclature confusing. Extensive ancillary pathology studies are required for appropriate diagnosis.
Pyoderma Gangrenosum‐Like Cutaneous T‐Cell Lymphoma
Authors: Piliang M. , McDonnell J. , Tuthill R. , Libecco J.
Published: August 2010

A 25‐year‐old man presented with a large, undermined, violaceous ulcer with hemorrhagic crust on his nose for 1 year. It began as a “pimple”. He had similar lesions on his scalp, abdomen and groin. His sister has Crohn’s and his mother has rheumatoid arthritis. Screening blood tests and CT scans revealed no underlying disease. The clinical impression was pyoderma gangrenosum. Biopsies from the nose and abdomen revealed dense superficial and mid‐dermal perivascular lymphocytic infiltrate composed of enlarged, atypical lymphocytes with focal epidermotropism and epidermal necrosis. Immunohistochemistry revealed the infiltrate was primarily CD3 positive T‐cells without deficiency of CD4, CD7 or CD8. CD30, TIA and Granzyme were not detected. A T‐cell receptor gamma gene rearrangement was detected. Flow cytometry was negative. This is a case of pyoderma gangrenosum‐like cutaneous T‐cell lymphoma, a rare form of cutaneous lymphoma that clinically resembles PG, but histologically and immunohistochemically is cutaneous T‐cell lymphoma. Although rare, PG‐like ulcers should be added to the list of atypical manifestations of CTCL. This case highlights the need to evaluate all atypical lymphocytic infiltrates thoroughly with immunohistochemistry and gene rearrangement. The diagnosis must be made with caution as proliferative clones of lymphocytes can be found in true PG.
Cyclin D1 Expression in Melanocytic Lesions of the Skin
Authors: Ramirez J.A. , Diaz L.K. , Guitart J.
Published: August 2010

Background: Progression through the cell cycle is controlled by cyclins, cyclin‐dependent kinases and cyclin‐dependent kinase‐inhibitory proteins. The role of cyclin D1 in the development, progression and prognosis of melanomas is controversial. The goal of this study is to evaluate the role of cyclin D1 in benign and malignant melanocytic lesions of the skin. Methods: A total of 101 melanocytic lesions of the skin including compound nevi (21), intradermal nevi (18), melanoma in situ (3), primary invasive melanoma (30), and metastatic melanoma (29) were evaluated for cyclin D1 overexpression by immunohistochemistry. The following tiered system was used for scoring: 0% of cells with nuclear staining (score 0), 1–19% nuclear staining (score 1), 20–49% nuclear staining (score 2), and 50% or greater nuclear staining (score 3). Results: The average score for primary melanomas was significantly higher compared to nevi (p = 0.0046), and for in situ melanomas compared to primary invasive melanomas (p = 0.011). There was slightly higher level of expression in compound nevi versus intradermal nevi. Conclusion: Our study indicates that cyclin D1 expression is increased in malignant compared to benign melanocytic lesions. Further studies are needed to ascertain the biological role of cyclin D1 in melanocytic lesions of the skin.
The First Known Case of Seconday Syphilis in a Heart Transplant Recipient with an Extraordinary Number of Spirochetes Found on Skin Biopsy
Authors: Rubin A. , Grossman M. , Silvers D.
Published: August 2010

A sixty‐nine‐year‐old male patient, without a significant prior medical history, presented with a rapidly enlarging, 2 cm non‐tender nodule on the right lower eyelid. The lesion persisted in spite of an incision and drainage. Following an excision, the histology revealed a diffuse infiltrate of atypical mononuclear cells within the dermis. The cells were large, monomorphic, with irregular to convoluted nuclei, prominent nucleoli, amphophilic cytoplasm. They were very mitotically active. Immunohistochemical stains for CD45, CD3, and CD30 were strongly positive. Pancytokeratin, CD20, and ALK (Anaplastic Lymphoma Kinase fusion protein) were negative. The histopathologic diagnosis was CD30 (Ki‐1) positive anaplastic large cell lymphoma. The margin was positive for involvement by lymphoma. The lesion was re‐excised with no evidence of residual involvement by lymphoma. A primary cutaneous anaplastic large cell lymphoma was favored over systemic involvement based on the clinical presentation of a single eyelid nodule and ALK negativity. He was referred to a hematology‐oncologist for further management. Anaplastic large cell lymphoma is a distinctive type of malignant lymphoma with a relatively favorable prognosis. It frequently involves the skin, however, to the best of our knowledge, presentation of this lymphoma type as a single lesion on the eyelid is extremely rare.
Hypomelanosis of ITO Associated with Precocious Puberty
Authors: Rutland B. M. , Horenstein M. G.
Published: August 2010

Background: There are only two reported cases of hypomelanosis of Ito (HI) associated with precocious puberty. Here we report a third case, and the first one to be autopsied. Design: A 5‐year‐old female with HI, intractable seizures and mental retardation presented with gray vaginal discharge and bacterial vaginosis. The patient subsequently died from neurologic complications and was autopsied. Results: Post‐mortem examination revealed pigmentary mosaicism following the lines of Blaschko and advanced development of vulvar labia, pubic hair, and breast buds. Other significant autopsy findings included conical teeth, patchy alopecia, macrosomia (body weight and height above 95th percentile), and macrocephaly with megalencephaly (brain 1850 g). The uterus and ovaries were unremarkable. Epidermis had decreased melanocytes in hypopigmented areas. Skin fibroblast karyotype was normal. Conclusion: The two previous case reports indicate that the mechanism for precocious puberty in HI may be either biochemical, as in McCune‐Albright Syndrome, or independent of GnRH. The mechanism of the precocious puberty in our case is most likely central.