bluuebunny/crossref_metadata_2025 huggingface dataset:
Major basement membrane components in Kaposi's sarcoma, angiosarcoma and benign vascular neogenesis
Authors: Dictor Michael , Bendsöe Nils , Runke Sheila , Witte Marlys
Published: April 2006

Recent cell biologic studies have emphasized the importance of the basement membrane (BM) and its molecular components in angiogenesis. We immunostained 60 angioproliferative lesions (angiosarcoma, sclerosing hemangioma of skin, pyogenic granuloma, capillary hemangioma, lymphangioma, glomangioma and granulation tissue) and 23 cases of Kaposi's sarcoma (KS) for the major macromolecular components laminin, collagen type IV, fibronectin and heparan sulfate proteoglycan (HSPG). Normal structures served as aggregate controls in each group, and semiquantitative scoring reflected the degree of consistency of staining about blood and lymphatic endothelium and vascular sheath (pericyte/smooth muscle) within and peripheral to each lesion. Benign and reactive vasoproliferations consistently maintained immunoreactivity for each BM component around endothelium and sheath components of blood vessels. Angiosarcoma showed from 20 to more than 60% less consistent immunoreactivity by comparison, although the score variances were greater than for non‐malignant lesions. Staining about blood vessel endothelium was both strong and consistent among histologic stages in KS with the exception of HSPG, which was weakly immunoreactive in all stages. Marked selective HSPG loss was characteristic only of KS and normal lymphendothelium, and in the light of evidence for a role for HSPG in the assembly and maintenance of BM, suggests that reduced HSPG may be responsible for the loss of ultrastructural integrity of perivascular BM in both.
Basaloid folliculolymphoid hyperplasia with alopecia as an expression of mycosis fungoides (CTCL)
Authors: Kossard S. , White A. , Killingsworth M.
Published: April 2006

Follicular mucinosis, papules, cysts and comedones have been previously described as expressions of follicular involvement by mycosis fungoides. We report a patient with mycosis fungoides who developed extensive alopecia. Multiple scalp biopsies showed perifollicular and intrafollicular infiltrate of lymphocytes but no evident follicular mucinosis. On transverse sections many of the follicles showed an absence of differentiation towards hair sheath, canal, sebaceous gland or hair formation, but instead formed undifferentiated basaloid structures. These basaloid structures showed transition from atrophic telogen follicles to hypertrophic basaloid islands infiltrated by lymphocytes, resembling the pattern previously described in cutaneous lymphadenoma. Immunophenotyping showed a predominance of helper T‐cells which, on ultrastructural examination, showed cerebriform nuclei. The unusual histological findings in our case may be analogous to the hyperplasia seen in sweat glands in syringotropic mycosis fungoides (syringolymphoid hyperplasia), and we propose the term basaloid folliculolymphoid hyperplasia to describe this feature. Basaloid follicular hyperplasia has been previously described as a component of follicular mucinosis but may apparently develop in the absence of overt mucinosis.
Desmosomal dissolution in Grover's disease, Hailey‐Hailey's disease and Darier's disease
Authors: Hashimoto Ken , Fujiwara Keiko , Tada Joji , Harada Masashi , Setoyama Mitsuru , Eto Hiakru
Published: April 2006

Proteins involved in the formation of desmosomes and simpler adherens junctions were studied in three types of non‐immune acantholytic diseases; specifically, four cases of Grover's disease (GD), one case of Hailey‐Hailey's disease (HMD) and one case of Darier's disease (DD), and these were compared to two cases of immune‐mediated acantholytic disease pemphigus vulgaris (PV). The proteins studied included: 1. The intracellular desmosomal proteins, desmoplakin I and II and plakoglobin; 2. The intercellular desmosomal proteins, desmoglein and CD44; and 3. vinculin, which is a major intracellular protein of the simpler aherens junctions. In GD, HHD and DD, immunostaining showed a loss of desmoplakin I and II and plakoglobin from the desmosomes, and a diffuse staining in the cytoplasm. In contrast, in pemphigus vulgaris, these proteins seemed intact and were localized to dot‐like spots on the cell surface. Also, desmoglein, and CD44 were slightly affected in GD, and moderately affected in HHD and DD. Absence of desmosomal attachment plaques, the lack of labeling with desmoglein in the affected desmosomes and a diffusion of the labels into cytoplasm were demonstrated with electron microscopy using an immunogold technique. In PV, desmoglein III is one of the target antigens for the autoantibodies in this disease and was only partially preserved in a small number of lesional cells, while CD44 was mostly preserved. Vinculin was intact in GD, HHD and DD, but was lost in PV. This study, our previous work, and that of others, suggest that: 1. In GD, HHD and DD, the proteins of the desmosomal attachment plaque are primarily affected; 2. In PV, the intercellular glycoproteins are primarily involved; and 3. Simple adherens junctions are intact in GD, HHD and DD, but are damaged in PV.
Epithelial markers and differentiation in adnexal neoplasms of the skin: an immunohistochemical study including individual cytokeratins
Authors: Demirkesen Cuyan , Hoede Nikolaus , Moll Roland
Published: April 2006

Applying immunohistochemical procedures for the detection of eight different cytokeratin (CK) polypeptides and other differentiation markers, we compared the staining patterns of normal cutaneous structures with those of benign adnexal tumors (n=65). Syringomas exhibited a marker pattern highly reminiscent of that seen in normal dermal eccrine ducts (EMA in peripheral cells, CK 10 in intermediate cells, and CK 6, CK 19, and CEA in luminal cells). Nodular hidradenomas exhibited complex patterns suggesting relationship between tumor cells, including clear cells, and normal secretory coil cells (CK 7, CK 8, CK 19, and EMA); however, dermal‐duct and epidermoid differentiation were also detectable. In both cylindromas and spiradenomas, zonal staining patterns were apparent: modified myoepithelial cells were positive for smooth‐muscle‐type actin, while the luminal cells mainly expressed cluctal markers (CK 6 and CK 19) and, less prominently, secretory‐coil markers including CK 7. Eccrine poromas exhibited a widespread reaction for CK5/6 and EMA, analogous to peripheral dermal duct cells, but focal maturation toward inner‐ductal and secretory‐coil cells was also demonstrable. The staining pattern observed in trichoepitheliomas resembled that of the outer but not the inner root sheath. In conclusion, the detailed marker profiles obtained in the present study have broadened our understanding of the differentiation and nature of these highly singular tumor types.
Lipomembranous changes in nodular‐cystic fat necrosis
Authors: Pujol Ramon M. , Wang Chin‐Yao , Gibson Lawrence E. , Daniel Su W. P.
Published: April 2006

Three cases of nodular‐cystic fat necrosis presenting with focal lipomembranous changes are reported. The lesions consisted of solitary (cases 1 and 3) or multiple (case 2) subcutaneous nodules on the upper (case 1) or lower (cases 2 and 3) extremities which had evolved over weeks to years. At surgical excision, solitary or multiple, freely mobile nodules within a cystic cavity were observed. Histologically, encapsulated fat nodules showing variable amounts of necrosis without marked inflammatory changes were present. Focal lipomembranous changes were observed in some nodules. Our observations seem to support the concept that lipomembranous changes are nonspecific and uncommon patterns of fat necrosis caused by a wide variety of local or systemic events that may cause a compromise in the blood supply of the subcutaneous tissue.
Multiple cutaneous myxomas
Authors: Murphy Christine M. , Grau‐Massanés Manuel , Sanchez Ramon L
Published: April 2006

An 11‐year‐old Hispanic female was referred for evaluation of multiple asymptomatic papules which had slowly developed since age two. The patient had no significant medical history and no family members, including an older sibling, were similarly affected. Physical examination revealed multiple 2–6 mm flesh‐colored to erythematous papules over the posterior scalp, trunk, and extremities, predominantly in a midline distribution. No lentigines, blue nevi, or evidence of endocrine ab‐normalities were noted. Echocardiogram was normal with no evidence of myxoma. Six cutaneous biopsies showed myxomas, as evidenced by well‐circumscribed dermal tumors composed of stellate, dendritic cells embedded in a mucinous stroma. Special stains and electron microscopy confirmed the H&E findings. Immunoperoxidase staining for Factor XIIIa was positive in the dendritic tumor cells, suggesting a relationship with dermal dendrocytes. This patient represents a case of multiple cutaneous myxomas without other components of Carney's complex of myxomas, spotty pigmentation, endocrine overactivity, and a variety of uncommon tumors. A long‐term follow‐up is indicated since some of the above cited elements of the syndrome could appear over time.
Idiopathic solitary neuroma of skin with unusual histologic changes
Authors: Ahn Sung Ku , Choi Eung Ho , Won Jin Hyoung , Lee Seung Hun
Published: April 2006

We report herein a case of idiopathic solitary neuroma with vascular proliferation and neurofibroma‐like features. Clinically, the skin lesion was a 0.7 cm nodule without tenderness on die forearm. Histologically, there was vascular proliferation in the upper dermis, some neural structures among the proliferative vasculature in the mid dermis and large bundles of neural structures extending in various directions in the mid and deep dermis (resembling neurofibroma). Special stains, such as Masson's trichrome and Luxol fast blue, and immunohistochemical studies, including S‐100 protein, neuron‐specific enolase (NSE), vimentin, desmin, factor‐VIII related antigen and epithelial membrane antigen (EMA), were added for this very rare case.
Kimura's disease and angiolymphoid hyperplasia with eosinophilia: New observations from immunohistochemical studies of lymphocyte markers, endothelial antigens, and granulocyte proteins
Authors: Helander Steven D. , Peters Margot S. , Kuo Tseng‐long , Daniel Su W. P.
Published: April 2006

Kimura's disease (KD) typically presents as large subcutaneous masses in young Oriental males. It is characterized by deep inflammation with vascular proliferation, lymphocytic nodules with subcutaneous germinal centers, fibrosis, and edema. In comparison, angiolymphoid hyperplasia with eosinophilia (ABLE) occurs in all races and the lesions usually are smaller and more superficial. The causes of diese two diseases are debated.

We compared histologic features of 4 cases of KD with 22 cases of ALHE and studied expression of endothelial antigens and lymphocyte markers as well as localization of eosinophil, mast cell, and neutrophil granule proteins in lesional tissue. T‐cell lymphoid aggregates with well‐formed B‐cell germinal centers occurred in KD, and nodular and diffuse T‐cell infiltration with small B‐cell clusters occurred in ALHE. Endothelial proliferation was more pronounced in KD, lacking the atypical histiocytoid endothelial cells characteristic of ALHE. Many intact eosinophils infiltrated lesions in both diseases, although KD had less extracellular granule protein deposition than ALHE. Intact mast cells were seen in both diseases. There was neutrophil elastase staining of occasional scattered intact cells but no extracellular deposition. Compared with KD, ALHE is more varied in its clinical, histopathologic, and immunohistochemical features.
Immunohistochemistry of dermatofibromas and benign fibrous histiocytomas
Authors: Prieto Victor G. , Reed Jon A. , Shea Christopher R.
Published: April 2006

Dermatofibromas (DF) are common, benign skin tumors composed predominantly of cells having elongated nuclei and very scant cytoplasm (i.e., fibroblasts) and capillaries in a collagenous stroma. Some authors distinguish DF from benign fibrous histiocytomas (BFH), which are composed of cells with round to oval nuclei and abundant cytoplasm (i.e., histiocytes). In general, this group of tumors expresses factor XIIIa but not the antigen recognized by MAC 387. However, immunohistochemical differences specifically between DF and BFH have not been reported.

We have studied the immunophenotype of 23 lesions having morphologic features predominantly either of DF (17 cases) or BFH (6 cases) using antibodies against desmin (muscle marker), α‐smooth‐muscle actin (muscle and myofibroblast marker), CD68 and HAM56 antigen (markers commonly expressed by macrophages, so called “histiocytic” markers), CD34 (a marker present in hematopoietic, vascular, and occasional dermal dendritic cells), and factor XIIIa (a transglutaminase present in many cells including dermal dendrocytes). Many spindle‐shaped cells expressed a‐smooth‐muscle actin while many large, round cells expressed the histiocytic markers. However, most lesions expressed at least focally both α‐smooth‐muscle actin and “histiocytic” markers. Thus a clear‐cut distinction between DF and BFH could not be made based on immunophenotype alone. Additionally, the prominent α‐smooth‐muscle actin immunoreactivity and desmin non‐reactivity suggests myofibroblastic differentiation in the spindle‐cell regions of these tumors, and indicates that expression of a‐smooth‐muscle actin cannot be used as definitive proof of muscle differentiation in spindle‐cell tumors. We conclude that DF and BFH are not discrete entities, but represent polar expressions of one nosologic entity exhibiting both myofibroblastic and “histiocytic” differentiation.
Halo nevus or halo phenomenon? A study of 142 cases
Authors: Mooney Maureen A. , Barr Ronald J. , Buxton M. Guy
Published: April 2006

One hundred and forty‐two (142) halo nevi were reviewed. For 66 cases the diagnosis of halo nevus was made both clinically and pathologically, and for 76 cases the diagnosis was based on histological grounds alone. The nevi were classified by type and by degree of atypia. Of the 142 nevi, all were compound, junctional, or intradermal nevi except for one case of a Spitz nevus and two cases that could not be further classified. For those with a clinicopathological diagnosis of halo nevus, 11% exhibited moderate atypia; 16% exhibited minimal atypia to only focally moderate atypia; 24% minimal atypia; and 49% exhibited no significant atypia. For those cases where the diagnosis was pathological only, there was also a broad spectrum of atypia identified, with 8% exhibiting focally severe or severe atypia. This study supports the concept that the halo nevus should not be regarded as a single clinicopathological entity, but rather that the halo phenomenon occurs in a wide spectrum of nevus types exhibiting a wide spectrum of histological atypia. The pathologist is therefore encouraged to classify halo nevi on the basis of the nevus cell population alone, using whatever classification normally utilized.
Basal cell carcinoma of the sole
Authors: Roth Mark J. , Stern Jere B. , Haupt Helen M. , Smith Robert R.L , Berlin Stephen J.
Published: April 2006

Basal cell carcinoma (BCC) of the plantar surface of the foot is rare, with only 22 previously reported cases. This clinico‐pathologic study is based on 20 cases pf BCC of the plantar surface and plantar‐like surfaces from adjacent lower lateral and medial aspects of the foot, submitted to a large podiatric laboratory from 1986 through June 1992 (total specimens for this period = 518,624; total BCC of lower extremities, below knee = 53). There were 15 women and 5 men. The average patient age was 73 years, with a range from 52 to 92 years. The duration of the lesion before diagnosis was 2 months to 12 years, with an average of 2 years. Three patients had a history of trauma. Podiatric clinical diagnoses included BCC (4), SCC (3), soft tissue tumor (2), nevus (1), granuloma (1), keratosis (2), verucca (1), and psoriasis (1). Follow‐up information was available on 10 patients; all were free of disease up to 64 months, with an average follow‐up of 15.7 months. Three of 20 BCC showed predominant histologic patterns characteristic of fibroepithelioma of Pinkus (FEP). An additional three BCC showed focal or suggestive patterns of FEP. Fourteen tumors showed ordinary BCC histologic patterns. No multicentric‐superficial or morphea like BCC were observed. The relatively high incidence of FEP in BCC of the sole correlates with abundant sweat glands and lack of hair follicles on the plantar surface, in accordance with the recent proposal that FEP derives its histologic pattern from the spread of BCC down eccrine ducts, eventually replacing them with solid strands of tumor.
Toxic epidermal necrolysis
Authors: Akosa A. B. , Elhag A. M.
Published: April 2006

Toxic epidermal necrolysis (TEN) is a rare dermatological emergency which is caused by drugs and results in a high morbidity and a mortality rate of 20‐30%. Ten confirmed cases of TEN were retrieved and the sweat glands were examined. Abnormalities of the sweat duct were found in all the cases and included basal vaculopathy, increased lymphocytic infiltration, basal apoptosis, basal cell hyperplasia and necrosis of the duct. Destruction and loss of the distal duct was present in 40% of the cases and was accompanied by dilatation of the proximal duct. In all cases, the proximal duct was involved to a lesser degree and in continuity with the distal duct, supporting the possibility of cytokine action. The secretory gland was normal. The presence of a significant reduction of sweat ducts in a disease process that involves 30‐100% of the total body surface area is of clinical importance.
The use of Michel's transport medium for immunofluorescence and immunoelectron microscopy in autoimmune bullous diseases
Authors: Vaughan Jones S.A. , Palmer I. , Bhogal B. S. , Eady R. A. J. , Black M.M.
Published: April 2006

We report the use of Michel's solution, already a well established transport medium, in the combined use of direct immunofluorescence (IMF) and pre‐embedding immunoelectron microscopy in 3 subepidermal bullous diseases ‐ bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA) and dermal binding linear IgA disease (LABD). Our studies demonstrated that electron microscopy of normal skin maintained in Michel's medium for up to 28 clays showed remarkable preservation of all components of the basement membrane zone, including the ultrastructure of the basal keratinocytes, dermoepidermal junction and papillary dermis. However, epidermal cell cytolysis occurred after just 48 hours.

Immunoelectron microscopy using a gold probe has enabled us to localise the immunoreactants in bullous pemphigoid, epidermolysis bullosa acquisita and dermal‐binding linear IgA bullous dermatoses. Our findings are comparable to and as equally reliable as those on immunoelectron microscopy of fresh skin biopsies with no loss of antigen deposition, and demonstrate an effective new use of a well established transport medium.
Histologic findings in acute HIV exanthem
Authors: Goldman Glenn D. , Milstone Leonard M. , Shapiro Philip E.
Published: April 2006

We describe a patient with acute HIV exanthem with papulo‐vesicular lesions and epidermal necrosis. We also review the literature regarding the histopathologic findings of acute HIV exanthem, which apears to be most commonly characterized by a perivascular lymphocytic infiltrate without epidermal change, but which may be associated with spongiosis, vacuolar alteration, or epidermal necrosis.
Median raphe cyst of the penis with ciliated cells
Authors: Romaní Jorge , Barnadas Maria A. , Miralles Julia , Curell Román , de Moragas José M.
Published: April 2006

Cystic lesions occurring on the ventral surface of the penis have been classified as median raphe cysts of the penis. They are lined by pseudostratified, columnar or stratified squamous cell epithelium, mimicking the epithelial lining of the male urethra. Ciliated cysts of the human skin are unusual. Cystic lesions containing ciliated cells have been noted to occur in the chest, neck, or head, and bronchogenic origin has been the most accepted explanation for its origin. Other reports show the presence of ciliated cysts on the lower extremities, and the mechanism of formation is still a debated question. A case of median raphe cyst of the penis containing ciliated epithelium is presented. The existing literature about these cutaneous lesions is reviewed, including the possible mechanisms believed to be involved in its origin.
Neoplasms with sweat gland differentiation express various glycoproteins of the carcinoembryonic antigen (CEA) family
Authors: Metze Dieter , Grunert Fritz , Neumaier Michael , Bhardwaj Ranjit , Amann Udo , Wagener Christoph , Luger Thomas A.
Published: April 2006

Carcinoembryonic antigen (CEA) is a well‐established marker for sweat gland differentiation in adnexal neoplasms. In contrast to previous assumptions, CEA does not represent a single oncofetal antigen but comprises a family of homologous glycoproteins, i.e. the classical CEA‐180, biliary glycoprotein (BGP), and non‐specific crossreacting antigens (NCA). The aim of the study was to evaluate the distribution of the respective glycoproteins of the CEA family in sweat gland neoplasms, as compared to normal sweat glands. A panel of mono‐specific antibodies was applied to a total of 83 samples of hyperplastic and cystic alterations of sweat glands, sweat gland neoplasms, and cutaneous metastases of different origin. Within a single group of neoplasms the immunohistochemical profile was rather consistent. Staining for both CEA‐180 and NCA‐90 indicated ductal differentiation of both eccrine and apocrine glands. Co‐expression of CEA‐180, NCA‐90, and BGP was consistent with differentiation towards the secretory part of eccrine glands or the transitional portion of proximal ducts. Neoplasms with signs of apocrine secretion showed a preferential immunoreactivity for NCA‐90 and BGP. In conclusion, a specification of the members of the CEA family may be of some value in the differential diagnosis of adnexal neoplasms, but not in the discrimination of sweat gland carcinoma from metastatic carcinoma.
IgA deposition in the skin of patients with alcoholic liver disease
Authors: Saklayen Mohammad G. , Schroeter Arnold L. , Nafz Mary Ann , Jalil Khalid
Published: April 2006

In patients with alcoholic liver disease, IgA deposits are often found in the liver, kidneys and skin. The present study was undertaken to determine the specificity, sensitivity and characteristics of IgA deposition in the skin of a group of alcoholic patients with or without overt liver disease, and compare these with findings in non‐alcoholic cirrhotics. Twenty‐six out of 28 patients with alcoholic cirrhosis had IgA deposition in the skin. In contrast, only 6 out of 11 patients who were alcoholic without any clinical liver disease and 3 out of 13 patients with non‐alcoholic cirrhosis of the liver had IgA deposition. In the control group, only 1 out of 52 patients with various dermatoses (excluding IgA dermatoses) had this IgA deposition. Unlike other IgA dermatoses, such as Henoch‐Schoenlein pnrpura or dermatitis herpetiformis, IgA deposition in alcoholic liver disease is characterized by its presence in the basement membrane of the eccrine secretory coils. This particular pattern of IgA deposition can be helpful in the diagnosis of alcoholic liver disease or alcoholism since the specificity is 100% with a sensitivity of 75%.
In vivo expression of the insulin‐like growth factor‐I (IGF‐I) receptor in congenital pigmented nevi
Authors: Hodak E. , Gottlieb A.B. , Colen S. , Anzilotti M. , Krueger J.G.
Published: April 2006

Growth of normal melanocytes, nevus cells and primary melanoma cells is enhanced by insulin/insulin‐like growth factor‐I (IGF‐I) in vitro. It has been shown that a melanoma cell line possesses the IGF‐I receptor which plays a role in activation of the chemotactic response. Little is known about the in vivo expression of the IGF‐I receptor and its role in melanocytic lesions. In an immunohistochemical study, we investigated the expression of IGF‐I receptor in frozen sections of congenital pigmented nevi from 10 patients (ages 8 months to 4 yrs) using the monoclonal antibody αIR3, which specifically recognizes the extracellular alpha subunit of the IGF‐I receptor. The proliferative activity of the nevus cells was examined by staining with Ki67 monoclonal antibody (reactive with all actively cycling cells). IGF‐I receptor was found to be widely expressed by the cell surface of the nevus cells. Membrane staining was occasionally stronger in the superficial portion of the congenital pigmented nevi. In contrast, Ki67‐positive cells were only sparsely scattered throughout the nevi with some tendency to localization to the superficial portion.

This study indicates that in vivo the IGF‐I receptor is widely expressed by congenital pigmented nevus cells. As opposed to keratinocytes, in which IGF‐I receptor expression defines the proliferation pool of the normal and disordered epidermis, the IGF‐I receptor is expressed by all nevus cells, irrespective of their proliferative status.

Further studies are needed to assess whether the IGF‐I receptor expression can serve as a marker for increased risk for development of malignancy in various types of benign melanocytic lesions.
Mdm‐2 is not induced by p53 in human keratinocytes in vivo
Authors: Burden A. D. , Stables G. I. , Campbell I. , Thomson W. , MacKie R. M.
Published: April 2006

Normal p53 protein protects the genome after DNA damage by delaying replication and allowing DNA repair, mdm‐2 is a recently discovered protein that controls p53 activity by binding to and inactivating p53 protein. A negative feedback loop has been suggested in which p53 induces mdm‐2 expression. We have shown that doses of ultraviolet B radiation that cause mild sunburn clinically, produce thymine dimers in keratinocytes detectable by immunocytochemistry. This causes an elevation of p53 protein without a concomitant p53‐mediated induction of mdm‐2.
Differences of bcl‐2 protein expression between Merkel cells and Merkel cell carcinomas
Authors: Moll Ingrid , Gillardon Frank , Waltering Stefan , Schmelz Monika , Moll Roland
Published: April 2006

The bcl‐2 gene, originally identified in B‐cell lymphomas, encodes for proteins which may assume oncogenic functions by blocking apoptosis. Bcl‐2 proteins are broadly distributed among various tissues, including epithelial ones. Within the skin, bcl‐2 is strongly expressed in melanocytes, but its further distribution is yet unclear. The Merkel cells, neuroendocrine‐epithelial cells of the skin, are present within the epidermis and hair follicles, mostly nerve‐associated, and are believed to be postmitotic and long lived. Possibly they give rise to the malignant Merkel cell carcinomas. In the present study we investigated the bcl‐2 expression on the protein level by means of immunohistochemical techniques including double confocal laser scanning microscopy, as well as on the RNA level by RT‐PCR techniques, in Merkel cells, Merkel cell carcinomas, and cell lines. Merkel cells were identified by double staining for cytokeratins 20 or 8/18. We demonstrate that fetal epidermal and dermal Merkel cells are immunostained for bcl‐2 protein, most of them clearly weaker than melanocytes. Adult Merkel cells also express bcl‐2 protein very heterogeneously, mostly weak. In contrast, Merkel cell carcinomas are visually strongly positive for bcl‐2 protein with some degree of heterogeneity. This is different from malignant melanomas in which bcl‐2 expression is reduced as compared to normal melanocytes. Bcl‐2 gene expression was also shown for Merkel cell carcinoma cell lines on both the mRNA and the protein level. Possibly bcl‐2 protein expression is downregulated during the life span of Merkel cells, arguing that they may succumb to a certain cell turnover. The comparably high bcl‐2 protein level in Merkel cell carcinomas may reflect peculiar biological and clinical characteristics.
Expression of basic fibroblast growth factor in desmoplastic melanoma
Authors: AL‐ALousi Suad , Carlson John A. , Blessing Karen , Cook Martin , Karaoli Themis , Bamhill Raymond L.
Published: April 2006

Basic fibroblast growth factor (bFGF) is an established growth factor for melanocytes and a potent angiogenic factor. The expression of bFGF was investigated in 23 desmoplastic melanomas. (DM) (12 males, median age 64 years, and 11 females, median age 54 years) by immunostaining of formalin‐fixed, paraffin‐embedded sections with high‐affinity purified antibody raised against recombinant human bFGF (Scios Nova, Inc.). The tumors were characterized by level II invasion in 1 case (5%), level IV invasion in 11 cases (48%), level V invasion in 8 cases (35%), and indeterminate in 3 cases. bFGF expression was observed in 22 of 23 tumors (95%), either immune localized to tumor cell nuclei in 17 of 22 tumors (77%), or to the cytoplasm of tumor cells in 5 of 22 tumors (23%). Also in these cases, bFGF was strongly expressed in the nuclei of vascular endothelial cells. Maximal expression was noted in the peripheral blood vessels of 20 tumors (91%) versus intratumoral vessels of 13 DM (59%). In conclusion, the expression of predominantly nuclear bFGF by tumor cells in DM suggests a role in mediating the desmoplastic phenotype. In addition, the localization of bFGF to vascular cndothelium, particularly at the periphery of the tumor, may be relevant to tumor angiogenesis.
Immune‐associated cells in basal cell carcinomas of skin
Authors: Deng J.S. , Brod B.A. , Saito R. , Tharp M.D.
Published: April 2006

Increased numbers of mast cells (MCs) and lymphocytes infiltrating in basal cell carcinomas (BCCs) have been observed. The presence of these infiltrating cells has been considered a sign of an immunologic anti‐tumor response in the host, but the relationship of these two cell populations has not been examined. To elucidate this possible relationship, 30 non‐ulcerated BCCs were analyzed. Frozen sections of the tumors were stained with monoclonal antibodies for Langerhans' cells, lymphocyte subsets and natural killer cells. Fluorescein isothiocynate (FITC) ‐aviclin as well as anti‐tryptase and anti‐CD45RO monoclonal antibodies were used on formalin‐fixed, paraffin‐embedded secdons for mast cell and T cell identification, respectively. B cells and natural killer cells were rarely observed in these tumors. MCs and T cells were quantified by direct enumeration and expressed as number of cells per high power field (hpf). FITC‐avidin and anti‐tryptase antibodies were equivalent in their ability to identify MCs. MC content in BCCs ranged from 1.0 to 31 cells/hpf. The number of T cells ranged from 0 to 50 cells/hpf with helper/suppressor cell ratios of 0.2 to 10. There was no correlation between helper/suppressor ratios and mast cell numbers; however, an inverse relationship was observed between the numbers of T cells and the number of mast cells in these tumors. These studies indicate that T cells and MCs are the primary immune cell populations responding to BCCs, and that decreased numbers of T cells are associated with more aggressive tumors.
Infundibulocystic basaloid neoplasm
Authors: de Eusebio Esther , Yus Evaristo Sánchez , Bran Eduardo López , Rojo Sonsoles , Rueda María , del Cerro Marta
Published: April 2006

Infundibulocystic basal cell carcinoma was described in 1987 as a new type of basal cell carcinoma with follicular differentiation. A great controversy followed this description, mainly about the malignant or benign character of this neoplasm and the distinction from other tumors with follicular differentiation. We present two new cases of this neoplasm: the first one had the typical features of this entity, except for the absence of stroma; the second one showed in the deep portion basaloid nodules similar to those of a nodular basal cell carcinoma. We review the criteria adduced to establish the malignant character of this neoplasm and conclude that both the nosology and biological behavior of this neoplasm with follicular differentiation remain to be determined.
Mid‐dermal elastolysis: a pathological and ultrastructural study of five cases
Authors: Neri Iria , Patrizi Annalisa , Fanti Pier Alessandro , Passarini Beatrice , Badiali‐De Giorgi Lucilla , Varotti Claudio
Published: April 2006

The aim of this study was to evaluate the presence of inflammatory phenomena and elastic fiber phagocytosis in mid‐dermal elastolysis. The pathological and ultrastructural features of 5 Caucasian female patients (ranging from 26 to 40 years) with acquired diffuse asymptomatic areas of skin wrinkling have been reviewed. The clinical features of all cases were characteristic of this condition and only in one patient were erythematous urticaria‐like, non pruriginous patches also observed. In 4 cases a history of prolonged sun bathing was present and in 3 cases there was a short history of oral contraception. The pathological study confirmed the typical absence of elastic fibers in the mid‐reticular dermis. In two cases elastic fibers were still detectable in the periadnexal dermis. Hematoxylin and eosin sections showed a mild perivascular infiltrate in two cases, while in three patients histiocytes were scattered among collagen bundles. Multinucleated giant cells containing fragmented elastic fibers were detectable in one patient. Ultrastructural analysis revealed large mononuclear cells with phagocytic aspects toward elastic fibers in all cases.
Malignant peripheral nerve sheath tumor of the skin: a superficial form of this tumor
Authors: Misago Noriyuki , Ishii Yutaka , Kohda Hiromu
Published: April 2006

A case of malignant peripheral nerve sheath tumor (MPNST) of the skin, which is a superficial form of this type of tumor, is described. Although our patient did not present the usual diagnostic criteria for MPNST, the clinicopathologic findings for both the initial and recurrent tumors were compatible with those of the ordinary type of this tumor and not with those of neurotropic melanoma or cellular schwannoma. The recurrent tumor presented progression compared to the low grade malignancy in the original tumor. Perhaps because of the superficial location of the tumor our patient showed an unexpected favorable outcome in spite of repeated recurrences. Reports indicate that, of the superficial forms, the ordinary type is still less frequently encountered than the epithelioid type. We also discuss the differentiation between MPNST of the skin and neurotropic melanoma.
Correlation between clonotypic T‐cell receptor beta chain variable region (TCR‐Vβ) gene expression and aberrant T‐cell antigen expression in cutaneous T‐cell lymphoma
Authors: Finn Daniel T. , Jaworsky Christine , Chooback Lilian , Jensen Pamela J. , Lessin Stuart R.
Published: April 2006

Immunohistochemical studies can augment the clinicopathologic diagnosis of cutaneous T‐cell lymphoma (CTCL). Our goal was to determine whether a panel of 11 T‐cell receptor (TCR) beta chain variable region (Vβ) monoclonal antibodies (moAbs) could consistently identify clonal T‐cell populations within CTCL skin infiltrates, and whether these cells exhibited aberrant T‐cell antigen expression. Biopsies from 24 CTCL and 3 parapsoriasis patients were analyzed. Of the 27 patients, 4 (15%) demonstrated T‐cell clonality by restricted TCR‐Vp moAb staining. The Vp+ restricted cells expressed aberrant antigen profiles. Overall, aberrant antigen profiles were detected in 18/24 (75%) CTCL patients. Vβ18 moAb crossreacted with a 85 kD protein produced by basal and suprabasal keratinocytes. We conclude: 1) Restricted TCR‐Vp expression correlated with aberrant T‐cell antigen profiles; 2) In the absence of a complete panel of TCR‐Vp moAbs, localization of aberrant T‐cell antigen expression can be useful in identifying malignant T‐cells within CTCL skin infiltrates; 3) The detection sensitivity and specificity of the currently available TCR‐Vβ moAbs may limit their utility to consistently detect clonal T‐cell populations in CTCL skin biopsies; 4) A 85 kD protein present on basal and suprabasal keratinocytes is recognized by Vβ18 moAb and may be related to immune function (s) of the epidermis.
The role of αEβ7 integrin (CD103) and E‐cadherin in epidermotropism in cutaneous T‐cell lymphoma
Authors: Dietz Stephanie B. , Whitaker‐Menezes Diana , Lessin Stuart R.
Published: April 2006

Adhesion molecules such as integrins and cadherins are thought to play a critical role in T‐cell migration and localization within the epidermis (epidermotropism). The purpose of this study was to correlate T‐cell expression of the integrin GD103 and E‐cadherin in cutaneous T‐cell lymphoma (CTCL). Serial sections of skin biopsies from 22 patients with CTCL and 13 with benign reactive dermatitis were stained with antibodies to CD4, CD103, and E‐cadherin by the avidin‐biotin peroxidase technique. CD 103 was expressed on single epidermotropic CD4+ T‐cells in 9/9 early stage (patch/plaque) CTCL and 6/10 reactive dermatitis biopsies. Less than 30% of dermal T‐cells expressed CD103. All 4/4 late stage (tumor) CTCL were GD103–. Epidermal aggregates of CD4+T‐cells (Pautrier's microabscesses) were CD103–. E‐cadherin was expressed on epidermal keratinocytes and follicular and sweat gland epithelia but not on T‐cells.

We conclude that CD 103 expression on cutaneous T‐cells parallels the degree of epidermotropism exhibited in both neoplastic and inflammatory disorders of the skin. E‐cadherin is not expressed on T‐cells infiltrating the skin. Further investigation is necessary to further elucidate the interaction between CD103 and E‐cadherin in facilitating trafficking of T‐cells into the epidermis.
The role of MT2 and anti‐bcl‐2 protein antibodies in the differentiation of benign from malignant cutaneous infiltrates of B‐lymphocytes with germinal center formation
Authors: Chimenti Sergio , Cerroni Lorenzo , Zenahlik Paul , Peris Ketty , Kerl Helmut
Published: April 2006

MT2/CD45RA and anti‐bcl‐2 protein (Bcl‐2) monoclonal antibodies are useful markers in distinguishing follicular lymphomas from reactive follicular hyperplasia of the lymph nodes. We examined biopsy specimens from 11 patients with primary cutaneous B‐cell follicle center lymphomas, 10 patients with cutaneous pseudolymphomas with germinal centers, and 6 patients with inflammatory infiltrates with germinal centers in non‐lymphoid cutaneous tumors (3 basal cell carcinomas, 2 malignant melanomas, and 1 solar keratosis), in order to evaluate the utility of MT2 and anti‐Bcl‐2 antibodies in differentiating benign from malignant germinal center cell proliferations in the skin. Immunohistochemical evaluation of MT2 and Bcl‐2 was focused exclusively on the reactivity of germinal center cells. Specific membranous MT2 positivity was found in 2/11 cutaneous follicle center lymphomas; a diffuse, non‐specific staining pattern was identified in 3/11 follicle center lymphomas and in 1/6 inflammatory infiltrates in non‐lymphoid tumors. A negative MT2 reaction was observed in 6/11 follicle center cell lymphomas, in all cases of pseudolymphomas and in 5/6 inflammatory infiltrates in non‐lymphoid tumors. Bcl‐2 positivity was detected only in 1/11 follicle center lymphomas. Germinal center cells in all other cases were Bcl‐2 negative. Our results suggest that MT2 and anti‐Bcl‐2 antibodies are only of limited value in differentiating primary cutaneous follicle center lymphomas from cutaneous pseudolymphomas with germinal centers.
Extranodal spread of anaplastic large cell (CD30+) lymphoma presenting as a cutaneous perivascular infiltrate
Authors: Derringer Gregory A. , Cotton Jenny P. , Melemed Allen S. , Treadwell Patricia A. , Hood Antoinette F.
Published: April 2006

Cutaneous lesions of anaplastic large cell (CD30+) lymphoma (ALCL) typically present as solitary or multiple ulcerated nodules. This tumor is histologically characterized by a diffuse dermal and sometimes subcutaneous infiltrate composed of bizarre, pleomorphic, neoplastic cells that may be occasionally multinucleated. We report a case of extranodal spread of ALCL to the skin in a 21/2‐year‐old boy presenting as a widespread papular eruption that on biopsy showed lymphoma restricted to the perivascular and periadnexal dermis.
Nuclear morphometry, immunohistochemical staining with Ki‐67 antibody and mitotic index in the assessment of proliferative activity and prognosis of primary malignant melanomas of the skin
Authors: Talve Lauri Arvo Ilmar , Collan Yrjö Urho Ilmari , Ekfors Tauno Olavi
Published: April 2006

Nuclear morphometry, immunohistochemical staining with Ki‐67 antibody and mitotic index were studied in primary cutaneous malignant melanomas. The number of Ki‐67 positive cells/200 tumor cells did not correlate with any nuclear morphometrical parameters, and it only approached but did not reach significant correlation with melanoma thickness according to Breslow. The nuclear area, short axis and long axis correlated with melanoma thickness, but the nuclear axis ratio (which reflects the sphericity of nuclei) and melanoma thickness did not show significant correlation. Mitotic index was higher in thick melanomas and in melanomas with high Ki‐67 positivity, large nuclear area, long nuclear short axis, and small nuclear axis ratio. In Cox's stepwise proportional hazard model, melanoma thickness and the nuclear axis ratio were significant independent prognostic factors for patient survival, while the nuclear area, short axis and long axis, gender, age, Clark level, mitotic index and Ki‐67 positivity lacked significant independent prognostic value.

The results suggest that the proliferative activity of tumor cells does not alone explain the great importance of tumor thickness as prognosticator in melanoma. The thickness of melanoma measured according to Breslow and the nuclear axis ratio are more efficient prognosticators in melanoma than parameters associated with proliferation.
Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty‐five cases
Authors: DeVito James R. , Merogi Athir J. , Vo Thao , Boh Erin E. , Fung Hank K. , Freeman Scott M. , Cockerell Clay , Stewart Kelly , Marrogi Aizen J.
Published: April 2006

Morphea (localized scleroderma), and lichen sclerosus et atrophicus (LSA) share common features with acrodermatitis chronica atrophicans (ACA), a known chronic form of borreliosis. These include similar histologic findings such as diffuse dermal fibrosis. These observations have led several investigators to consider the possibility of Borrelia burgdorferi (Bb) as a common etiologic factor among all of these diseases.

The aim of this study is to investigate the role of Bb in the pathogenesis of morphea and LSA, by assaying for its presence in lesional skin biopsies from patients with these diseases. We utilized the nested polymerase chain reaction (PCR) technique to selectively amplify a longer segment of a Bb‐specific somatic gene, on DNA from paraffin‐embedded, formalin‐fixed tissues. The results revealed no Bb‐specific DNA sequence in 28 specimens of morphea/scleroderma and 7 of LSA with varying stages of disease. Furthermore, confirmatory Southern blot of the PCR product, resulted in similar findings. These data seriously question the role played by this spirochete in the pathogenesis of morphea and LSA, at least in the southeastern part of the USA.
Apoptotic cell death in formation of vesicular skin lesions in patients with acquired zinc deficiency
Authors: Mori Hijiri , Matsumoto Yoshinari , Tamada Yasuhiko , Ohashi Masaru
Published: April 2006

We investigated the role of apoptotic cell death in the production of skin lesions in patients with acquired zinc deficiency. Nuclear condensation of keratinocytes was observed at an early stage of skin lesions in patients with zinc deficiency, especially around vesicular lesions. Nuclei of keratinocytes in perivesicular lesions of the epidermis were positively stained by the nick‐end labeling specific for fragmented DNA. Lewis Y antigen was also expressed on perivesicular lesions. On the other hand, there were no such positively stained cells in hyperkeratotic skin lesions of the patients. Therefore, it was suggested that apoptotic cell death might play a role in the formation of vesicular skin lesions in patients with zinc deficiency, but not in the formation of hyperkeratotic skin lesions.
Fibro‐osseous pseudotumor of the digit: a comparison to myositis ossificans by light microscopy and immunohistochemical methods
Authors: Sleater J. , Mullins D. , Chun K. , Hendricks J.
Published: April 2006

Fibro‐osseous pseudotumor of the digit is an unusual cutaneous process characterized histologically by a fibroblastic proliferation admixed with reactive/metaplastic osteoid formation. The osteoid formation can be florid and immature, mimicking the appearance of malignant osteoid‐forming neoplasms. Fibro‐osseous pseudotumor of the digit has histologic and clinical features in common with myositis ossificans. This has led many to consider the two to be synonymous. We studied three cases of fibro‐osseous pseudotumor, compared to five cases of myositis ossificans, using routine light microscopy and a battery of immunohistochemical stains.

Both entities displayed a “zoning” pattern of immature spindled areas admixed with more mature areas having osteoid metaplasia. This was more pronounced in myositis ossificans. In each lesion, the spindle cells stained positively for vimentin and actin. CD34 and Factor VIII highlighted the vasculature. No stromal staining for MAK‐6 (cytokeratin) or S‐100 was identified. Ki‐67, a proliferation marker, showed positive staining of the stromal cells in both lesions, which was strongest in the immature spindled areas. The immunohistochemical and histologic similarities of the lesions support fibro‐osseous pseudotumor of the digit being a cutaneous variant of myositis ossificans.
Ossifying fibromyxoid tumor of soft parts
Authors: Velasco‐Pastor A. Manuel , Martinez‐Escribano J. , del Pino Gil‐Mateo M. , Quecedo‐Estébanez E. , Fortea‐Baixauli J. Miguel , Aliaga‐Boniche A.
Published: April 2006

Ossifying fibromyxoid tumors (OFT) of soft parts are very rare neoplasms recently described by Enzinger et al. (1). They usually present as well‐circumscribed, slow‐growing, asymptomatic subcutaneous masses. A characteristic finding is a fibrous capsule and an incomplete peripheral shell of mature bone. Although most cases behave as benign tumors, a high rate of local recurrences have been described. We describe a 43‐year‐old male with a perianal subcutaneous tumor of 10 years evolution. The histopathology was compatible with OFT. Due to the subcutaneous location of OFF, both the dermatologist and dermatopathologist need to know about this rare tumor.