bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeat direct immunofluorescence (DIF) test, using 1 M NaCl treated skin, in the subepidermal autoimmune bullous diseases that contain IgG at the dermal epidermal junction
Authors: Barnadas Ma A. , Gelpi C. , Curell R. , de Moragas J. M. , Alomar A.
Published: August 2006

Knowledge of autoimmune bullous diseases has greatly increased with the recognition of new entities, and the use of the direct immunofluorescence (DIF) using 1 molar per liter of sodium chloride (1 M NaCl) treated skin has been proposed. To estimate the frequency with which the different DIF patterns are present, we performed a systematic study of the skin or oral mucosa samples in which linear deposits of IgG at the basement membrane zone were detected by routine DIF in the last 6 years. The DIF tests were done on 56 samples before and after splitting the epidermis from the dermis with 1M NaCl. In 40 biopsies (72%) IgG was found on either the epidermal side or on both sides after 1M NaCl split. These cases corresponded to bullous pemphigoid (n=33), herpes gestationis (n=5) and cicatricial pemphigoid (n = 2). In 6 cases (10.7%), IgG deposits were observed only on the floor, five corresponding to bullous pemphigoid and one to bullous pemphigoid‐like eruption induced by amoxicillin. Repeat direct immunofluorescence using 1M NaCl split skin indicates that at least 12% of patients who were initially diagnosed as bullous pemphigoid, may in fact suffer a different entity, requiring other techniques to achieve the right diagnosis. This test can be a useful routine screening for autoimmune bullous diseases.
Pseudoporphyria associated with Relafen therapy*
Authors: Magro C. M. , Crowson A. N.
Published: August 2006

Various oral medications including nonsteroidal anti‐inflammatory drugs (NSAIDs) have been associated with pseudoporphyria, although the pathogenetic basis has not been elucidated. A novel NSAID nabumetone (Relafen) has become popular because of its minimal gastrointestinal side effects, Its association with pseudoporphyria is not reported save for its listing in the Physician's Desk Reference (PDR) as a possible side effect. Biopsies of lesional skin from 4 patients manifesting blisters and erosions on the hands and face within 4 months of starting nabumetone were submitted for light microscopic and immunofluorescent (IF) studies. Histories and serology were obtained. Two patients had rheumatoid arthritis (RA), 1 had mixed connective tissue disease (MCTD), and I received diltiazem. All 4 had antinuclear antibodies. Characteristic clinical, light microscopic and IF features in the absence of elevated urine porphyrin levels confirmed a diagnosis of pseudoporphyria in all 4 patients. Biopsies in three patients showed features attributed to underlying connective tissue disease (CTD), including ectasia of the superficial vascular plexus, mild leukocytoclastic vasculitis, superficial and deep perivascular lymphocytic infiltrates with dermal mucinosis, granular deposition of IgM along the dermoepidermal junction indicative of a positive lupus band test, and of IgG and C5b‐9 within keratinocytes. Nabumetone (Relafen) can provoke pseudoporphyria; an underlying CTD diathesis may be a predisposing factor.
Microcystic adnexal carcinoma arising in the setting of previous radiation therapy
Authors: Antley C. A. , Carney M. , Smoller B. R.
Published: August 2006

While there are several reports of microcystic adnexal earcinoma developing in patients within sites of previous therapeutic irradiation, this relationship is not well described in the dermatologic literature. We report a case of a 42‐year‐old man with a remote history of therapeutic irradiation following surgical resection of periorbital rhabdomyosarcoma. Subsequently, he developed multiple basal cell carcinomas and a microcystic adnexal carcinoma within the field of irradiation. The histologic features were those of a classic microcystic adnexal carcinoma, with well differentiated nests and cords of keratinocytes displaying follicular and ductular differentiation infiltrating diffusely into the reticular dermis. Dense fibrosis was present surrounding the neoplastic keratinocytes. Nuclear atypia and mitotic figures were not identified. A carcinoembryonic antigen (CEA) stain demonstrated glandular differentiation. It is important for dermatologists to be aware of the apparent relationship between the rare microcystic adnexal carcinoma with its innocuous scar‐like clinical appearance and prior local radiation therapy.
Syphilis in an HIV infected patient misdiagnosed as leprosy
Authors: Fonseca Eduardo , García‐Silva Jesús , del Pozo Jesús , Yebra María Teresa , Cuevas Jesús , Contreras Félix
Published: August 2006

A 42‐year‐old man with uveitis and a widespread cutaneous eruption, histopathologically characterized by dermal granulomatous infiltrates with perineurial invasion, was incorrectly diagnosed and treated as having borderline leprosy. Further studies demonstrated secondary syphilis and human immunodeficiency virus (HIV) inlection. Standard penicillin therapy resolved his cutaneous and ocular lesions. Reports on clinical and pathological findings of active syphilis in HIV infected patients are scarce but this case and isolated previous case reports suggest that granulomatous infiltrates might be a common feature in secondary syphilis with short evolution in HIV infected palients.
Birt‐Hogg‐Dubé‐syndrome and Hornstein‐Knickenberg‐syndrome are the same. Different sectioning technique as the cause of different histology
Authors: Schulz Tilman , Hartschuh Wolfgang
Published: August 2006

The auiosomal dominant inherited syndromes of Horornstein and Knickenberg (HKS). and Birt, Hogg and Dubé (BHDS) are both characterized clinically by the overall spread of multiple flesh coloured papules of the skin. However, it is a mailer of debate il cnlonic neoplasms ladenomas as well as adenocarcinomas) are associated findings in the HKS or rather in the BHDS. Furthermore, histological differences are said to exist between the skin lesions in the two syndromes: whereas perifollicular fibromas were described m the HKS, fibroiolliculomas and trichodiscomas were found in the BHDS. In the present study, we report on a father and his daughter in whom we initially diagnosed a BHDS. We then examined a greater number of the papular lesions in histologic sections cut vertically as well as horizontally to the epidermis. Our results indicate that the histologic differences between the skin lesions in the two syndromes are artificial ones, caused by interpretation of different sectioning planes, and that consequently HKS and BHDS are the same. Therefore, it is necessary to look for colonic polyps in the syndrome in question, regardless if one prefers the name HKS or BHDS for it.
Hsp72 antigen expression in the proliferative compartment of involved psoriatic epidermis
Authors: Edwards M. J. , Nazmi N. , Mower C. , Daniels A.
Published: August 2006

Oxidative damage to growth regulatory proteins has been implicated in the aetiology of psoriasis. However, the transient synthesis of heat shock proteins has been shown to protect cells against the adverse effects of oxidative and other forms of physiological stress. This study has used an hsp72 monoclonal antibody to measure inducible 72 kDa heat shock protein expression in heat stressed normal human skin and established plaque psoriasis. Hsp72 was detected in the basal and suprabasal layer cells of heat‐stressed normal skin, and in 12 involved psoriasis lesions. Hsp72 expression was not delected in unstressed normal skin or in 12 cases of uninvolvcd psoriasis. Immunoprecipitation and Western blotting of cell lysates from heat stressed normal skin and involved psoriasis lesions confirmed the presence of a 72 kDa polypeptide with hsp72 immunoreactivity. The MIB‐1 monoclonal antibody was used to determine the proliferative fraction of normal and involved psoriastic epidermis. The Ki67 antigen was localised to the nuclei of basal and suprabasal layer cells of normal and involved psoriatic epidermis. Involved psoriatic epidermis contained a higher number of proliferating keratinocytes when compared with normal skin. The study has also demonstrated a strong correlation between hsp72 expression and keratinocyte proliferation in involved psoriatic epidermis (r=0.864, p<0.001). We believe that the 72 kDa inducible heat shock protein performs a protective function in the proliferative compartment of normal and involved psoriatic skin.
Subcutaneous trichoblastoma
Authors: Kaddu Steven , Schaeppi Herwig , Kerl Helmut , Soyer H. Peter
Published: August 2006

We have recently observed three examples of solitary trichoblastomas (TB) with unusual histopathologic features characterized mainly by numerous aggregations of basaloid cells limited to the subcutis. The three trichoblastomas with unusual features were identified from a large scries of 38 solitary TB cases collected over a period of 20 years. Clinically, all three neoplasms presented in men (49, 52, and 62 years old) as solitary, 1‐ to 1.5‐cm skin‐colored nodules situated on the scalp, face, and lower arm, respectively. Histopathologically, they showed numerous, smooth‐bordered aggregations of basaloid cells limited to the subcutis and surrounded by a sclerotic and partly hyalinized stroma. Multiple sections revealed no connections of basaloid aggregations to the overlying epidermis or pre‐existing follicular structures. All three cases displayed rather unusual morphologic growth patterns, including areas of variously sized, nodular aggregations of basaloid cells and extensive foci of elongated, thin columns and branching cords of basaloid cells. A striking feature in the stromal component in two cases was the presence of large, prominent areas of hyalinization and sclerosis. Characteristically, all three neoplasms showed numerous foci with rudimentary follicular germs and papillae. Cytomorphologically, the basaloid cells exhibited dark staining nuclei with large prominent nucleoli and scanty, pale or eosinophilic cytoplasm. Variable number of mitotic figures (2‐4 mitoses per high‐power field) and single necrotic cells were noted. In one case, small, foci of necrosis en masse were observed. Follow‐up data after total excision in all three cases (80, 69, and 6 months) revealed no local recurrences. In light of our observations, we suggest that subcutaneous TB represents a rare variant of solitary TB. Besides the exclusive subcutaneous location, this neoplasm also displays a constellation of particular histopathologic features, namely, rather complex epithelial growth patterns and stroma with prominent foci of sclerosis and hyalinization.
CD56+ blastic transformation of chronic myeloid leukemia involving the skin
Authors: Kaddu Steven , Beham‐Schmid Christine , Zenahlik Paul , Kerl Helmut , Cerroni Lorenzo
Published: August 2006

We report on two patients with chronic myeloid leukemia (CML) who presented blastic transformation involving the skin, with leukemic infiltrates showing unusual morphologic and immunohistologic characteristics. Both patients were elderly men with a 36‐month and a 40‐month history of CML, respectively. They presented with disseminated, reddish to violaceous papules and plaques (case 1), and with localized reddish nodules on the left temporal area (case 2). Concurrent features of blastic transformation in the bone marrow were observed in one patient (case 1). Histopathologic examination of skin lesions revealed similar features in both cases. There was a moderate to dense dermal infiltrate composed mainly of medium‐sized atypical mononuclear myeloid precursor cells with only few relatively well‐differentiated cells of the granulocytic series. Histochemical staining for naphthol‐ASD‐chloroacetate esterase revealed strong positivity (>50% of neoplastic cells) in case 2 and only scattered positivity (<10% of neoplastic cells) in case 1. Immunohistologic analysis performed on paraffin‐embedded sections showed in both cases variable reactivity of neoplastic cells for leucocyte common antigen (CD45), lysozyme, myeloperoxidase, CD11c, CD15, CD43, CD66, CD68, HLA‐DR, and the neural cell adhesion molecule (NCAM) CD56. A negative reaction was observed for CD3, CD34, and TdT. The immunohistologic findings were remarkably similar to those reported for acute myeloid leukemia (AML) with monocytic differentiation (French‐American‐British [FAB] classification, subtype M4)’. Examination of blasts from the bone marrow performed in one patient (case 1) revealed a similar phenotype also with CD56 expression. In conclusion, our observations show that specific cutaneous infiltrates in CML may show morphologic and immunohistochemical characteristics similar to those observed in AML with monocytic differentiation. Moreover, specific cutaneous manifestations of CML may express CD56.
Malignant rhabdoid tumor beside benign skin mesenchymal neoplasm with myofibromatous features
Authors: García‐Bustínduy Marta , Álvarez‐Arguelles Hugo , Guimerá Francisco , García‐Castro Candelaria , Sánchez‐González Rosalba , Hernández Norberto , Diaz‐Flores Lucio , García‐Montelongo Rafael
Published: August 2006

Only a few reports of primary cutaneous rhabdoid tumors have been published. We describe the case of a 3‐month‐old female patient who developed a rhabdoid type cutaneous sareomatoid neoplasm in her upper back, close to a benign myofibromatous proliferation of infancy. The lesion was studied both by light microscopy and immunohisto‐chemically. Flow cytometry was performed showing a DNA diploid profile of the malignant tumor. The pathological findings suggest a mesenchymal origin (hemangiopericytic or myofibroblastic type) for both tumors. The patient was surgically treated, but she died nine months later.
Dermatofibroma parasitized by Leishmania in HIV infection: a new morphologic expression of dermal Kala Azar in an immunodepressed patient
Authors: Castellano Victor M. , Rodriguez‐Peralto J. L. , Alonso S. , la Fuente E. Gómez‐De , Ibarrola C.
Published: August 2006

Visceral leishmaniasis is a protozoan infection that may complicate the course of patients with human immunodeficiency virus (HIV). Dermatofibroma is a cutaneous fibrohistiocytic lesion considered neoplastic by some authors and inflammatory by others. Eruptive dermatofibromas have been described in patients with HIV infection or with other altered immunity situations. We present the case of a 32‐year‐old, HIV‐positive man with visceral leishmaniasis who complained of the appearance of a cutaneous lesion in the leg formed by the coexistence of dermatofibroma and Leishmania parasitic colonization. As far as we know, this type of association has not been reported previously. We consider that the dermatofibroma could have developed as an unusual form of fibrohistiocytic reaction to leishmania. From a practical approach, we recommend the search of leishmaniasis in dermatofibroma in immunosupressed patients.
Infection with parapoxvirus induces CD30‐positive cutaneous infiltrates in humans
Authors: Rose Christian , Starostik Petr , Bröcker Eva‐B.
Published: August 2006

Expression of CD30 is a distinct feature of B‐ or T‐cell activation, found in Hodgkin's disease, large cell anaplastic lymphoma, lymphomatoid papulosis, as well as in certain viral infections such as human T‐lymphotropic virus type I, HIV, hepatitis B and C virus, and Epstein‐Barr virus. Here, we report highly proliferative CD30‐positive cutaneous infiltrates in 3 patients with Milkers's nodules, adding parapoxvirus infection to the spectrum of CD30‐positive benign lymphoproliferations.
The epidermotropic mycosis fungoides associated α1β1 integrin (VLA‐1, CD49a/CD29) is primarily a collagen IV receptor on malignant T cells
Authors: Bank IIan , Rapman Edward , Shapiro Raisa , Schiby Ginette , Goldberg Iris , Barzilai Aviv , Trau Henry , Gur Hanan
Published: August 2006

Several of the βa integrin receptors [very late antigen (VLA) molecules] for extracellular matrix (ECM) proteins are expressed by malignant T cells in cutaneous T‐cell lymphoma (CTCL). We evaluated the function of VLA‐1. a β1 integral specifically expressed in epidermotropic mycosis fungoides (MF), in CD4+ leukemic T cells (Jurkat line). We found that Jurkat cells adhere significantly to collagens only after their activation with phorbol 12‐myristate 13‐acetate (PMA). However, the adhesion to collagen IV (but not to collagen I) of Jurkat cells selected for expressing increased levels of VLA‐1 (with unchanged levels of VLA‐2, the second collagen integrin receptor) was significantly enhanced relative to that of “VLA‐1 low” cells. Monoclonal antibody (mAb) 1B3.1, directed against the collagen binding domain of VLA‐1, inhibited adhesion to collagen IV and to collagen I by 36.67%±5.25% and 18%±4.32%, respectively (p<0.05), whereas the inhibition by anti‐VLA‐2 mAb PIE6 was comparable on both collagens (25%±7.48% and 36.3%±0.94%, respectively; p<0.09). Immunohistochemical studies of skin biopsies from 10 untreated MF patients showed that in all cases at least 10% of the lymphocytes residing in the epidermis are VLA‐1+VLA‐2‐. While not directly applicable to MF, the demonstrated functions of VLA‐1 in leukemic Jurkat cells, together with its expression in MF skin, suggest a role for VLA‐1 integrins in epidermotropism in a small proportion of leukemic MF cells.
Apoptosis, Fas and Fas‐ligand expression in melanocytic tumors
Authors: Sprecher Eli , Bergman Reuven , Meilick Ahuvah , Kerner Hedviga , Manov Lena , Reiter Irena , Shafer Yan , Maor Gilah , Friedman‐Birnbaum Rachel
Published: August 2006

Impaired regulation of apoptosis is known to be associated with the development of various forms of cancer. Fas binding ro its ligand. Fas ligand (Fas‐L), has been shown to trigger apoptosis in various cell types. Fas‐L is expressed by melanoma cells and has been suggested to play a role in melanoma escape from immune surveillance. In the present study, we assessed apoptotic activity and examined Fas and Fas‐L expression in malignant melanomas, Spitz nevi and ordinary melanocytic nevi. We evaluated apoptotic activity using terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick end labeling. Apoptotic activity was found to be minimal in melanomas and moderate in Spitz nevi. In contrast, common nevi demonstrated, significant levels of apoptosis in the deep parts of the tumor. Fas was found to be expressed by all Spitz nevi, most melanocytic nevi and approximately half of the malignant melanoma specimens. Fas expression was also significantly more pronounced in Spitz nevus cells as compared with, the two other tumors. The anti‐Fas‐L antibody was found to stain all three melanocytic tumors. Staining was shown to be stronger and more frequent in melanoma cells as compared to the nevus cells. Using the Spearman test, no significant correlation between Fas‐L expression in melanoma cells and apoptosis in MM‐infiltrating mononuclear cells was found, suggesting that Fas‐L expression in melanoma cells may not be instrumental in their ability to escape immune mechanisms of defense. In contrast, increased levels of apoptosis in the deep parts of melanocytic nevi may reflect and possibly contribute to their benign nature.
Immunohistochemical analysis of cytokeratin expression in multiple eccrine hidrocystoma
Authors: Ohnishi Takamitsu , Watanabe Shinichi
Published: August 2006

The histologic diagnosis as eccrine hidrocystoma may contain some other cysts which do not originate from the eccrine sweat glands. Some authors have suggested that true eccrine hidrocystoma does not exist. However, multiple eccrine hidrocystoma (Robinson type) is a distict clinical entity which is characterized by multiple translucent papules around the eyelids which appear in warm weather. Cytokeratin expression in 8 cases of multiple type of unequivocal eccrine hidrocystoma was analyzed immunohistochemically. Immunoreactivities in our cases were similar to those of eccrine dermal ducts. Therefore, we confirmed that these tumors were derived from the eccrine dermal duct, not from the other appendages, and that true eccrine hidrocystoma exists.
Inflammatory metastatic melanoma
Authors: Florez Angeles , Sánchez‐Aguilar Dolores , Peteiro Carmen , Peñaranda José M. Suárez , Toribio Jaime
Published: August 2006

An 87‐year‐old woman developed erythema, induration and tenderness of the skin overlying each breast. One year before, she had undergone an axillary lymph node dissection because of metastases from melanoma. The primary site was unknown. A skin biopsy showed pigmented tumor nests within the dermal lymphatic vessels, and immunohistochemistry confirmed the melanocytic origin. The diagnosis of inflammatory metastatic melanoma was made.
Cytokeratin 15 expression in trichoepitheliomas and a subset of basal cell carcinomas suggests they originate from hair follicle stem cells
Authors: Jih Debra M. , Lyle Stephen , Elenitsas Rosalie , Elder David E. , Cotsarelis George
Published: August 2006

Trichoepitheliomas and many basal cell carcinomas appear to arise from the hair follicle, and in particular from the hair follicle bulge. This histogencsis is suggested from both morphological and immunohisto‐chemical studies on tumor cells and siroma. Epithelial stem cells are thought to be important in tumorigenesis, and we previously localized a population of stem ceils to the bulge area of the outer root sheath. We recently identified an anti‐CD8 monoclonal antibody (DAKO clone C8/144B) that cross‐reacts with cytokeratin 15 (K15), and serves as a specific marker for the bulge. In this study, we screened a Series of trichocpitheliomas (n=13), basal cell carcinomas (n=37) and a variety of other skin tumors with this antibody, All trichocpitheliomas (100%) showed keratin 15 expression, while only a subset of basal cell carcinomas (27%) was K15‐positive. Epidermal tumors, including squamous cell carcinomas, were K15‐negative. Tumors of follicular derivation such as proliferating trichilemmal cysts were also K15‐positive, while others such as pilomatricoma were K15‐negative. Expression of K15 in trichoepitheliomas, some basal cell carcinomas and other follicular tumors suggests that these tumors are related to hair follicle stem cells in the bulge.
A reappraisal on the modes of cell death in pilomatricoma
Authors: Nakamura Toshitsugu
Published: August 2006

The modes of cell death in pilomatricoma were analysed using 27 nodules. The shadow cells with lost nuclei and preserved cytoplasms were morphologically considered to be derived from basaloid cells via transitional cells, which showed gradual loss of nucleic acid by Feulgen reaction and methylgreen‐pyronin stain and no nuclear fragmentation. This process was regarded as cell death associated with terminal differentiation into hair. Amorphous debris among the shadow cells contained many fragmented nuclei (apoptotic bodies), which were directly derived from basaloid cell layer focally undergoing apoptosis and did not have any transition to transitional cells. Although in situ 3′‐tailing reaction for a detection of dying cells labelled both transitional cells and apoptotic bodies in the amorphous debris, these two components were considered to be on different histogenetic pathways. Immunostainings for the Bcl‐2 family revealed no expression of Bax, Bad or Bak protein in any components, whereas Bcl‐2 protein was detected in the periphery of basaloid cell layer, but not in the transitional or shadow cells. These results indicate that there are two different modes of cell death in pilomatricoma: i) terminal differentiation into shadow cells; and ii) conventional apoptosis observed as amorphous debris.
Intravascular and diffuse dermal reactive angioendotheliomatosis secondary to iatrogenic arteriovenous fistulas
Authors: Requena Luis , Fariña Ma Carmen , Renedo Guadalupe , Alvarez Ana , Yus Evaristo Sánchez , Sangueza Omar P.
Published: August 2006

Reactive angioendotheliomatosis is a rare benign process that has been mainly described in patients with systemic infections, such as subacute bacterial endocarditis or tuberculosis, and in association with intravascular deposition of cryoproteins. Histopathologically, it is characterized by a proliferation of endothelial cells within vascular lumina resulting in the obliteration of the involved vessels. Another rare variant of reactive angioendotheliomatosis has been described in the lower extremities of patients with severe peripheral vascular atherosclerotic disease. It consists of violaceous and purpuric plaques histopathologically characterized by diffuse prolifrration of endothelial cells interstitially arranged between collagen bundles of the reticular dermis. This second variant has been named diffuse dermal reactive angioendotheliomatosis. We report two patients with reactive cutaneous angioendotheliomatosis appearing distally to arteriovenous fistulas used for hemodialysis because of chronic renal failure. The first patient showed intravascular reactive angioendotheliomatosis, while the second one had purpuric plaques that were characterized histopathologically by diffuse dermal angioendotheliomatosis. Both patients showed an arteriovenous “steal” syndrome with distal ischemia, and it is possible that a local increase of vascular endothelial growth factor, as is the case in hypoxia situations, induces the endothelial proliferation. To the best of our knowledge, cutaneous reactive angioendotheliomatosis has not been previously described in association with arteriovenous shunts.
Quantitation of intraepidermal T‐cell subsets in formalin‐fixed, paraffin‐embedded tissue helps in the diagnosis of mycosis fungoides
Authors: Nuckols J. Dean , Shea Christopher R. , Horenstein Marcelo G. , Burchette James L. , Prieto Victor G.
Published: August 2006

Differentiation between mycosis fungoides (MF) and cutaneous inflammatory processes can usually be made on clinical and histologic grounds. In difficult cases, immunohistochemical studies can he helpful since MF infiltrates usually contain a predominance of CD4+ lymphocytes, while most inflammatory lesions usually have a mixture of CD4+ and CD84‐ lymphocytes. However, this determination has traditionally required the use of frozen tissue, thus severely limiting its usefulness. Recently, antibodies that differentially label CD4+ and CD8+ lymphocytes in formalin‐fixed, paraffin‐embedded tissue have become available (OPD4 and C8/144B respectively. DAKO (Carpinteria, CA, USA). This study tests the utility of these antibodies in the pathologic diagnosis of MF and inflammatory lesions with significant exocytosis. In 9 cases of MF for which both frozen and fixed tissues were available for comparison, the OPD4+ cell count in fixed tissue was significantly lower than the Leu‐3a+ cell count in frozen tissue. Also, the C8/144B+ cell count in fixed tissue was higher than the Leu‐2a+ cell count in frozen tissue, although this difference was not significant statistically. In a larger series for which only fixed tissue was available, epidermal CD4:CD8 ratios were significantly greater in 23 MF cases (mean 4.0±4.76) than in 35 inflammatory cases (mean 0.6±0.42; p = 0.001). Thus, although the studied antibodies appear to detect different epitopes in frozen versus paraffin‐embedded tissue, demonstration of an elevated CD4:CD8 ratio in fixed tissue supports the diagnosis of MF, and is a helpful adjunct to routine histopathology.
Polymerase chain reaction‐denaturing gradient gel electrophoresis (PCR/DGGE)‐based detection of clonal T‐cell receptor γ gene rearrangements in paraffin‐embedded cutaneous biopsies in cutaneous T‐cell lymphoproliferative diseases*
Authors: Andersen William K. , Li Ning , Bhawan Jag
Published: August 2006

Polymerase chain reaction (PCR)‐based amplification of T‐cell receptor (TCR)‐γ genes is a novel technique that can detect a clone of T cells comprising less than 1% of the total T cells in a lymphoid infiltrate1. Besides greater sensitivity than Southern blotting, this technique can be performed with smaller quantities of lower molecular weight genomic DNA as template. We retrospectively analyzed 12 paraffin‐embedded biopsies of cutaneous T‐cell lymphoma (CTCL), 1 case suspicious for CTCL, 1 case of granulomatous slack skin, and 8 cases of inflammatory skin diseases to determine if PCR‐denaturing gadient gel electrophoresis (PCR‐DGGE) analysis can detect TCR‐γ gene rearrangements on paraffin‐embedded specimens. we were able to amplify Bγ1‐8 TCR sequences in each case and detected a dominant clone in 9 of 12 cases of CTCL and in granulomatous slack skin. We analyzed Vγ9 sequences in 9 cases of CTCL and detected a dominant clone in 4 cases. This study demonstrates that PCR‐DGGE can easiy by applied retrospectively to cutancous biopsies of lymphoproliferative diseases when fresh itssue is not available.
Differences in sialyl‐Tn antigen expression between keratoacanthomas and cutaneous squamous cell carcinomas
Authors: Jensen Petter , Clausen Ole P. F. , Bryne Magne
Published: August 2006

Keratoacanthoma and squamous cell carcinoma are common skin tumors, especially in immunosuppressed transplant recipients, but the distinction between these two types of epidermal neoplasia may be difficult. Sialyl‐Tn (Sia‐GalNAc‐O‐Ser/Thr) is a cell surface carbohydrate associated with hyperplasia in squamous epithelium, and correlated with poor prognosis in several human adenocarcinomas. Twenty‐seven keratoacanthomas and 29 cutaneous squamous cell carcinomas were examined for the expression of sialyl‐Tn and of the Ki67 epilope, the latter a marker for cell proliferation. By immunohistochemistry, basaloid tumor cells at the periphery of tumor nests showed some degree of sialyl‐Tn expression in 16 keratoacanthomas (59%), while only three squamous cell carcinomas (10%) showed sialyl‐Tn‐positive basaloid tumor cells (p<0.001). Keratinized, differentiated tumor cells were more often sialyl‐Tn‐positive in keratoacanthomas (89%) than in squamous cell carcinomas (31%) (p<0.001). A striking sialyl‐Tn‐positivity in the basal cell layer was found in a border zone directly adjacent to most tumors of both types (88 and 88%). By immunohistochemical examination of parallel sections and by double immnnofluorescence, sialyl‐Tn antigen expression was primarily seen in cells that did not express Ki67, although some overlap was present. Keratoacanthomas from transplant recipients did not differ in sialyl‐Tn expression compared to those from non‐immunosuppressed patients. The results indicate that sialyl‐Tn expression is not directly related to cell proliferation, but rather to cellular features of post‐mitotic cells, and that sialyl‐Tn is not associated with a malignant phenotype. Sialyl‐Tn may be linked to tumor regression, as seen in keratoacanthomas.
Ectopic breast tissue and breast‐like sweat gland metaplasias: an overlapping spectrum of lesions
Authors: Pfeifer John D. , Barr Ronald J. , Wick Mark R.
Published: August 2006

There are many similarities in the morphology of benign and malignant lesions of the sweat glands and the breasts. The recently described cutaneous mammary‐like sweat glands, also known as mixed sweal glands or apoeccrine glands, are also a likely source of selected proliferations that closely mimic those of the breast. We present three cases of breast‐like lesions arising in the skin that demonstrate the ways in which the morphologic and pathologic continuum of the mammary glands, cutaneous mammary‐like glands, and sweat glands can produce difficulties in precise diagnosis. The examples demonstrate that an anatomic location outside the milk line does not preclude the diagnosis of ectopic mammary tissue, and that lesions closely resembling those of the breast may also arise outside the milk line from conventional sweat glands or mixed sweat glands. The concept of homologous lesions of the breast, breast‐like glands and sweat glands, in which morphology is partially mirrored by biochemical similarities, provides a perspective for classification of problematic cases of breast‐like cutaneous lesions.
Confocal reflectance imaging of folliculitis in vivo: correlation with routine histology
Authors: González Salvador , Rajadhyaksha Milind , González‐Serva Aldo , White W. Matthew , Anderson R. Rox
Published: August 2006

Near‐infrared confocal reflectance microscopy (CM) is a high‐resolution non‐invasive imaging technique with promising future in dermatology. A pustular lesion from a 35‐year‐old male with a known history of folliculitis was non‐invasively viewed with CM and later biopsied. Optical sections were correlated with routine histology, This optical technique allows us to view non‐invasively transverse skin sections to a conirolled depth in real time. In the CM images, tissue can be visualized with cellular and subeellular detail as shown by imaging infiltrating neutrophils (PMNs) within the subcorneal pustule of a superficial folliculitis in vivo.
Expression of complement regulator proteins in primary and metastatic malignant melanoma
Authors: Weichenthal Michael , Siemann Ute , Neuber Karsten , Breitbart Eckard W.
Published: August 2006

The expression of complement regulatory antigens C3b/C4b receptor, (CD35) membrane cofactor protein (CD46), decay accelerating factor (CD55), and homologous restriction factor 20 (CD59) was determined immunohistochemically on ten primary malignant melanomas, 16 metastatic lesions, and ten melanocytic nevi. All of the melanocytic new and 9/10 primary melanomas showed both expression of CD46 and CD59. In one primary melanoma lacking CD46, expression of CD35 could be delected. In metastatic melanoma, 9/16 metastascs were CD46+/CD59+, two were CD46‐/CD59+, one CD46+/ CD59‐, and four CD46‐/CD59‐. Additionally, CD55 could he detected in two CD46 +/CD59 + metastases, and CD35 in one. Expression or lack of complement regulatory antigens did not correlate with the expression of GD2, GD3, HMB‐45 or S‐100. In conclusion, some cases of metastatic melanoma show loss of normal expression of complement regulatory proteins. This might have implications on the immune response or the efficacy of immune therapy in malignant melanoma.
Tools of the trade: statistical analysis in dermatopathology articles
Authors: Flotte Thomas J. , Duncan Lyn M. , Lerner Lisa H. , Mihm Martin C.
Published: August 2006

Statistical analysis of research results provides powerful tools for understanding the data from projects. A prospective review of the statistical methods utilized in 100 consecutive articles in the recent literature relevant to dermatopathology was performed. The majority of papers, 75%, did not contain statistical analyses. A wide variety of methods were utilized in the papers that did have statistical analyses including methods in the following categories: t‐test. contingency tables, multiple regression, multiple comparisons, nonparametric tests, life tables, and survival tests. Nine of the 25 papers utilizing statistical analysis had problems in the methods. These problems included treating categorical data as a continuous variable, multiple comparisons, subgroup analysis, and discordance of statistics and conclusions. It is important to understand the underlying assumptions of statistical methods to use the appropriate tets. These are tools of the trade for dermatopathology investigators.
Identification of mycobacterial DNA in cutaneous lesions of sarcoidosis
Authors: Li Ning , Bajoghli Amir , Kubba Asha , Bhawan Jag
Published: August 2006

Sarcoidosis is a multisystemic granulomatous disease of uncertain etiology. Recently, mycobacterial DNA especially Mycobacterium tuberculosis and Mycobacterium avium complex were detected in lung tissue and bronchial lavage fluid from patients with sarcoidosis by polymerase chain reaction (PCR) assays in 30% to 50% cases. Moreover, cell wall‐defective form (CWDF) acid‐fast bacteria have been isolated from skin lesions of patients with sarcoidosis which were later confirmed as M. avium complex by PCR assays. CWDF acid‐fast bacteria were also found to grow from the blood of 95% patients with active sarcoidosis demonstrating a mycobacterial origin similar to M. tuberculosis. In view of these reports, we investigated 20 cases of cutaneous sarcoidosis using PCR/restriction enzyme pattern analysis (PGR/REPA) to detect mycobacterial DNA from paraffin‐embedded skin biopsy samples. The method involves restriction enzyme analysis of nested PCR products obtained with primers encoding for the 65‐KDa protein common to all mycobacteria. Using three restriction enzymes, the mycobacterial DNA from PCR product was differentiated to the species level. All the 20 cases had clinical and histologic evidence of sarcoidosis. Special stains for fungi (PAS) and mycobacteria (Fite) were negative and no foreign body was identified on polaroscopic examination in any of the cases, The cell lysates of M. tuberculosis, Mycobacterium bovis, Mycobacterium avium‐intracellulare, Mycobacterium kansasii and Mycobacterium marinum from Centers for Disease Control (CDC) were used as standard control for PCR/REPA. Eight cases of foreign body granuloma, seven normal skin samples from the margin of surgical excisions and 5 cases of dermatitis were used as negative controls, and 4 cases of cutaneous tuberculosis were used as positive controls. Mycobacterial DNA was detected by PCR in 16 of the 20 cases of sarcoidosis. PCR/REPA subtyped 8 of these to M. tuberculosis complex (2 cases), M. avium‐intracellulare (4 cases), M. kansasii (2 cases) while the other 8 cases were non‐tuberculous mycobacteria. All four cases of cutaneous tuberculosis were positive by PCR and had a typical M. tuberculosis PCR/REPA pattern. Mycobacterial DNA was not detected in any of the negative controls. Our results demonstrated that mycobacterial DNA is present in 80% of cutaneous lesions of sarcoidosis and these mycobacteria may play a role in the pathogenesis of sarcoidosis.
Epidermal calprotectin in drug‐induced toxic epidermal necrolysis
Authors: Paquet P. , Piérard G. E.
Published: August 2006

Calcium ions (Ca++) in excess alter cell viability. Their potential role in drug‐induced toxic epidermal necrolysis (TEN) was investigated. Thirteen TEN patients were biopsied at the site of early billions lesions and on clinically normal‐looking skin al least 2 cm distant from blisters. Immunohistochemistry was applied using the mouse monoclonal antibody Mac 387 recognizing the cytosolic protein complex L1 (calprotectin). The L1 antigen is a calcium‐binding protein expressed by human granulocytes, monocytes‐macrophages and injured epidermis, but not by normal epidermis and other cells harboured in the skin. The majority (8/13) of TEN samples from apparently non‐involved skin expressed the L1 antigen in a patch‐like pattern inside the epidermis where inflammatory cells were scant or absent. As assessed by computerized image analysis of TEN bullous skin, the intensity of the L1 expression in the epidermis was not statistically correlated with the amount of the infiltrating inflammatory cells (Mac 387+ macrophages, UCLH1+ T lymphocytes and Factor XIIIa+ dendrocytes) present in the dermis and in the epidermis. Such findings suggest a key role for keratinocytes in the production of the L1 calcium‐binding complex. As the L1 complex formation is a calcium‐dependent process, one of the first biological events in TEN could be a dramatic increase in keratinocytes intracelular Ca++ concentration following damage by the involved drug metabolites. The ultimate toxic cell dysregulation would result from the disturbance in the intracellular Ca++ homeostasis.
Neuroendocrine differentiation of a metastatic basal cell carcinoma in a patient with basal cell nevus syndrome
Authors: Tawfik Ossama , Casparian J. Michael , Garrigues Ned , Smith Shondra , Kestenbaum Thelda , Chamberlin Fran , Khan Qamar S.
Published: August 2006

A 48 year‐old white male with basal cell nevus syndrome presented with a metastatic basal cell carcinoma with neuroendocrine features. The tumor manifested aggressive behavior, having deep local invasion and metastases to para‐aortic lymph nodes and bone. Neuroendocrine differentiation has rarely been associated with basal cell carcinoma. The histologic, immunohistochemical, and electron microscopic studies of this rare tumor are described.
Ultrastructural localization of alpha‐3 integrin subunit in malignant melanoma and adjacent epidermis
Authors: Schumacher O. , Schaumburg‐Lever G.
Published: August 2006

Eight cases of malignant melanoma were studied by immunohistopathology and immunoelectron microscopy. α3 integrin localization was documented in malignant melanoma cells, basal and suprabasal keratinocytes, melanoeytes. blood vessels and in basement membrane material. In melanoma cell membranes and, to a lesser extent, the interior of melanosomal vesicles were labeled. In addition, neighbouring cells such as basal and suprabasal keratinocytes and melanocytes showed strong α3‐integrin expression. The labeling was much stronger in the plasma membrane than in the cytoplasm. Enclotheliul cells showed stronger labeling of the cytoplasm than of the plasma membrane. In some cases we found increased flocculent material surrounding melanoma cells or nests that seems to contain basement membrane protein components, specifically α3‐integrin subunits. Compared to normal epidermis α3‐labeling was stronger in tissues of malignant melanoma.
Immunohistochemical characterization of pleomorphic giant cells in basal cell carcinoma
Authors: Cutlan Robert T. , Maluf Horacio M.
Published: August 2006

Over 20 cases of basal cell carcinomas with pleomorphic giant cells of the mononuclear or multinucleate type have been described. The nature of these cellular and nuclear changes has not been elucidated. Some authors found that these cells have phagocytic properties and others reported an aneuploid DNA content. We have seen milolic figures in some of these giant cells, and postulate that these cells are Capable of proliferation. Twelve cases of basal cell carcinoma with plenninrphic giant cells were examined using monoclonal antibodies recognizing the proliferating cell nuclear antigen (PCNA), Ki‐67, and bcl‐2 antigens. Expression of proliferation associated antigens in the giant cell population was higher than in the small cell population. Over expression of bcl‐2 was detected in both the small and giant cells in all cases. The results demonstrate that the giant tumor cells are cycling and express bcl‐2 protein in a manner consistent with basal cell carcinoma. The changes are unlikely to represent a senescent change as seen occasionally tn mesenchymal neoplasms.
Trichoepithelioma: a 19‐year clinicopathologic re‐evaluation
Authors: Bettencourt Miriam S. , Prieto Victor G. , Shea Christopher R.
Published: August 2006

Accurate histopathologie distinction between trichoepithelioma (TE) and basal cell carcinoma (BCC) may be challenging. From 97 cases diagnosed as TE during the period 1979–1997, 73 available cases were studied with regard to: 1) stroma; 2) retraction effect; 3) papillary‐mesenchymal bodies (PMB); 4) amyloid; 5) mitotic figures; 6) apoplotic cells; 7) inflammation; 8) granuloma; and 9) calcification. A judgment was made regarding diagnosis. The patients’medical records were subsequently reviewed for clinical features and possible recurrence. The diagnosis of TE was confirmed histologically in 48 (65%) of 73 cases. Fifteen cases (21%) were reclassified as BCC (RC‐BCC), eight other cases (11%) were reclassified as other lesions, and two additional cases (3%) could not be confidently classified as either TE or BCC. The most helpful differentiating features were the presence of retraction effect (in 100% of RC‐BCC vs. 37% of TE), myxoid stroma (in 80% of RC‐BCC vs. 12% of TE) and PMB (in 20% of RC‐BCC vs. 81% of TE). Unexpected findings in TE were detection of amyloid in 33%, apoplotic cells in 100%, and mitotic figures in 46%. Five of the 15 RC‐BCC have recurred (33%), whereas there have been no recurrences in the confirmed TE group. A constellation of hisiopathologic criteria may help lo discriminate problematic examples of trichoepithelioma from basal cell carcinoma.
Vasculitis‐induced membranous fat necrosis
Authors: Ramdial Pratistadevi K. , Chetty Runjan
Published: August 2006

Membranous fat necrosis (MFN) a distinct degenerative process of adipose tissue, is characterised by the presence of membranocystic lesions (MCLs) superimposed on a background of typical traumatictype fat necrosis. MCLs are cysts, of varying size and shape, thai are lined by an eosinophilic, crenulated membrane, having the staining properties of ceroid. Although MFN has been documented in varying systemic adipose tissue sites and in tumours, the pathogenesis of this pathological curiosity is unknown. To date, an ischemic basis for MFN has been the most proximate, and atherosclerosis and venous insufficiency, due to large and medium vessel disease, have been the most popular underlying clinical disorders. Although systemic vasculitis has been quoted as the underlying ischemic disorder in some patients, vasculitis has not been commented on nor demonstrated in tissue sections in association with MFN. In reporting vasculitis‐induced MFN, we document the occurrence of MFN in association with uncommon causes of vasculitis, namely: 1) Granulomaious vasculitis in a post‐herpetic zosteriform scar; 2) Cytoinegalovirus‐induced vasculitis in tie clinical setting of systemic lupus crythematosus; and 3) Lymphocytic vasculitis in a tetanus toxoid immunization site reaction.
Immunohistochemical observation of cytokeratins in keratinous cysts including plantar epidermoid cyst
Authors: Ohnishi Takamitsu , Watanabe Shinichi
Published: August 2006

Sixteen cases of epidermal cyst (EC) (6 cases of conventional EC and 10 cases of plantar epidermoid cyst (PEC)) and 9 cases of trichilemmal cyst (TC) were examined by an immunohistochemical technique using various antibodies against cytokeratins and human papilloma virus (HPV) in order to clarify their histogenesis. There was no difference in immunoreactivities between EC and PEC with or without HPV infection. In TC, the inner layers of the cyst wall were stained with the antibody E3 (CK17), and the outermost layer was stained with the antibodies 4.1.18 (CK8) and 170.2.14 (CK19). In PEC and EC, however, the cyst wall didn't react with these antibodies, and differentiation‐specific cytokeratins were expressed in the inner layer. These results confirmed that the immunoreactivities of PEC and EC were identical to those of normal epidermis or infundibulum, and that those of TC were similar to the outer root sheath between the lower infundibulum and isthmus. Although PEC has been recently reported to originate from eccrine ducts, there was a significant difference in immunoreactivities between PEC and eccrine ducts. Furthermore, on the basis of the fact that sole skin has no hair follicles, PEC was speculated to originate from epidermal implantation.
Outer root sheath acanthoma
Authors: Reichel Martin , Heilman Edward R.
Published: August 2006

The term “outer root sheath acanthoma” is proposed to specify a distinctive keratosis exhibiting outer root sheath differentiation. This lesion features anastamosing columns of keratinocytes emanating from the undersurface of the epidermis that respectively demonstrate, with progressive descent into the upper dermis, outer root sheath differentiation characteristic of the infundibulum, isthmus, stem and anagen bulb. In our patient, the lesion was solitary, and no associated systemic disease was evident. Outer root sheath acanthoma is a unique keratosis displaying all four types of tricholemmal differentiation, thus representing a true neoplasm of the entire outer root sheath.