Spindle cell squamous cell carcinoma arising in Bowen's disease: Case report and review of the published work

A 79‐year‐old Japanese woman presented with an ulcerated, brown‐red nodule in the center of a sharply demarcated, tan‐brown plaque situated on the left side of her right breast. Histologically, the plaque demonstrated an acanthosis with an intraepidermal epithelioma of Borst‐Jadassohn. Small oval nests of bland‐appearing basophilic cells in the periphery gradually enlarged into nests of various sizes and irregular shapes, composed of densely cohesive, atypical basophilic cells above the central nodule. The atypical keratinocytes shifted to atypical spindle cells beneath the acanthotic epidermis, penetrating deep into the subcutaneous tissue. In addition to vimentin and p63, the spindle cells were positive for several cytokeratin (CK) markers, including AE1/AE3, 34βE12 and CK5/6, which showed more intense signals closer to the epidermis. Basophilic cells in the clonal nests were positive for p63, AE1/AE3, 34βE12 and CK5/6. The MIB‐1 index was estimated at approximately 40–50% in both the bland‐appearing and the atypical basophilic cells. We describe the first case of spindle cell squamous cell carcinoma arising in an intraepidermal epithelioma expressed by clonal Bowen's disease, which was difficult to differentiate from clonal seborrheic keratosis.     

Desmoplastic seborrheic keratosis

Eleven cases of seborrheic keratoses with desmoplastic stroma and associated nests and cords of squamous epithelium simulating infiltrating carcinoma are presented. There were 7 males and 4 females ranging in age from 44 to 88 years (mean = 62). Eight cases were on the head and neck, one each on the lower and upper extremity, and one on the pubic area. Clinical diagnoses included seborrheic keratosis, squamous and basal cell carcinoma, and dermal nevus. Histologically, the lesions were characterized by exophytic growth pattern of basaloid and squamous cells, without cytologic atypia, and well-demarcated peripheral borders, typical for that seen in seborrheic keratoses. Squamous eddy formation with parakeratosis and spongiosis was present in all cases. Located within the body of the lesions were irregular nests and cords of squamous cells extending into the surrounding dermis with associated fibroblastic dermal proliferation trapping the epithelial nests, simulating invasive carcinoma. Immunohistochemically, the epithelial nests were cytokeratin positive and HPV negative, and the dermal stromal cells were vimentin positive and factor XIIIa, cytokeratin, and CD34 negative. Adjacent changes of carcinoma, trichilemmoma, verruca, or other adnexal neoplasm were not identified. Seborrheic keratoses may demonstrate desmoplastic changes analogous to that seen in desmoplastic trichilemmomas. Awareness of these changes in seborrheic keratosis will avoid misdiagnosis and excessive therapy.     

Expression of TWEAK in normal human skin, dermatitis and epidermal neoplasms: association with proliferation and differentiation of keratinocytes

Background: Tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) has been implicated in the pathogenesis of various inflammatory pathologies and cancer. We aimed to investigate its expression in normal human skin, inflammatory skin diseases and epidermal neoplasms. Methods: Immunohistochemistry for TWEAK was performed in samples of healthy skin, plaque psoriasis, lichen planus, prurigo nodularis, discoid lupus erythematosus, lichen sclerosus, seborrheic keratosis, common warts, actinic keratosis, Bowen's disease, keratoacanthoma and basal and squamous cell carcinoma. Double immunofluorescence was used to investigate co‐localization of TWEAK with cytokeratin‐10 and proliferating cell nuclear antigen (PCNA). Results: TWEAK was robustly expressed in the epidermis of healthy skin and decreased in inflammatory conditions, both in the context of epidermal hyperplasia and atrophy. Decreased TWEAK immunoreactivity was regularly observed in common warts, actinic keratosis and Bowen's disease, particularly in areas of marked proliferation as evidenced by PCNA‐positive nuclei. In squamous cell carcinoma, expression of TWEAK ranged from strong to completely absent, and it mostly corresponded with the expression of cytokeratin‐10. TWEAK was absent in keratoacanthoma and basal cell carcinoma. Conclusions: TWEAK is a constitutively expressed epidermal protein whose downregulation might be an early indicator of disturbed differentiation or pathologic proliferation of keratinocytes that accompany inflammatory and neoplastic skin diseases. Peternel S, Manestar‐Bla?i? T, Brajac I, Prpi?‐Massari L, Ka?telan M. Expression of TWEAK in normal human skin, dermatitis and epidermal neoplasms: association with proliferation and differentiation of keratinocytes.     

组织蛋白酶D在皮肤鳞状细胞癌、基底细胞癌和脂溢性角化病的组织表达及其意义

目的：观察组织蛋白酶D（cathepsinD，CD）在皮肤鳞状细胞癌（SCC）、基底细胞癌（BCC）、脂溢性角化病（SK）的组织表达，分析其表达差异及其意义。方法：用免疫组化SP染色法检测CD在15例SCC、15例BCC、14例SK及10例正常对照皮肤组织中的表达。结果：CD在正常皮肤组织表达为阴性．在SK、BCC、SCC瘤组织中表达依次升高，在SCC、SK之间表达有显著性差异（P〈0．05）；CD在SK、BCC、SCC间质细胞表达阳性率分别为85．7％、66，7％、33．3％。结论：CD的表达水平可能与SCC侵袭和转移有关。     

Seborrheic keratosis with pseudorosettes and adamantinoid seborrheic keratosis: two new histopathologic variants

Aims:  Seborrheic keratoses are the most common benign cutaneous neoplasms in adult and middle-age patients. There are six distinctive histopathologic variants of seborrheic keratosis, namely, acanthotic or solid, reticulated or adenoid, hyperkeratotic or papillomatous, clonal or nested, irritated and inflamed.
Methods:  We report two additional histopathologic variants of seborrheic keratosis.
Results:  One lesion showed abundant intercellular mucin, closely resembling to adamantinoma, and therefore was named adamantinoid seborrheic keratosis. The other one exhibited a peculiar distribution of the basaloid keratinocytes, which were arranged radially around small central spaces, resulting in pseudorosette formation.
Discussion:  To our knowledge, these two histopathologic variants of seborrheic keratosis have been not previously described in the literature.     

Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it from Bowen's disease and seborrheic keratosis

Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To date, there has never been a report focusing on dermoscopic features to distinguish HAS from BD and SK. We found the following dermoscopic findings to be characteristic of HAS: fine black dots/globules (75% of cases) and fine scales arranged annularly (100% of cases). In contrast, glomerular vessels, which are typically observed in BD, were not seen in any of the four cases. Cerebriform appearance and milia‐like cysts, which are typically observed in SK, were also not seen in any of the four cases. The existence of “scattered fine black dots/globules” and “fine scales arranged annularly”, and the absence of the glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS resembles BD or SK clinically, it can be distinguished from these by the characteristic dermoscopic features.     

Expression profiles of ProEx C and Ki67 in squamous cell carcinoma in situ of the skin and their relationship with human papillomavirus genotypes

Background: ProExC is a new marker for identification of precursor lesions of cervical carcinoma. Its utility in noncervical squamous cell carcinoma in situ (SCCIS) such as Bowen's disease (BD) and actinic keratosis (AK) where human papillomavirus (HPV) plays a role has not been elucidated. Our aim was to ascertain the immunohistochemical features and clinical utility of ProExC in SCCIS of the skin. Methods: HPV presence was tested in SCCIS (38 BD and 7 AK) using GP5+/6+ and Short PCR fragment (SPF) primers and subsequently genotyped. Histopathologic sections were stained for ProExC and Ki67. A set of non‐neoplastic skin proliferative lesions were included for immunohistochemical evaluation [14 psoriasis (PS) and 6 psoriasiform dermatitis (PSD)]. Results: HPV was detected in 18.9% BD. ProExC and Ki67 in the whole epidermis thickness was observed in 86.5 and 37.1% BD, respectively (p < 0.0001). ProExC and Ki67 were restricted to the lower third of the epidermis in PS and PSD. Conclusions: ProExC expression is not associated with HPV in SCCIS of the skin. Proliferating cells are better delineated in SCCIS by ProExC which may be useful to assess the extent of these lesions. Different immunohistochemical profiles seen in neoplasic and non‐neoplastic skin lesions suggest diverse alteration of cell‐cycle kinetics. Sánchez‐Hernández M, Conesa‐Zamora P, García‐Solano J, Corbalán‐Vélez R, Martínez‐Barba E, Pérez‐Guillermo M. Expression profiles of ProEx C and Ki67 in squamous cell carcinoma in situ of the skin and their relationship with human papillomavirus genotypes.     

Simple epithelial cytokeratin-expression in seborrheic keratosis

The cytokeratin expression of seborrheic keratosis was studied by means of immunohistochemistry and compared with that of normal human skin. The following findings were obtained in seborrheic keratosis: (1) a partial lack of high molecular weight cytokeratin (#1/68 kD, #10/56.6 kD) in all ten cases examined; (2) the detection of cytokeratin typical for simple epithelia (#8/52.5 kD, #18/45 kD, #19/40 kD) in eight of ten cases; and (3) the detection of cytokeratin #5/58 kD in suprabasal cells in 5 of 10 cases. An immunoelectron-microscopic investigation, using an anti-keratin antibody against cytokeratin #19/40 kD, revealed a whirl-like arrangement of keratin filaments within immunoreactive cells, in contrast to a linear, parallel arrangement in non-immunoreactive cells. Cells known to express cytokeratin typical for simple epithelia, such as sweat gland cells or Merkel cells, were not observed. The altered cytokeratin gene-expression in seborrheic keratosis may be attributable to de-differentiation of tumor cells or potential re-differentiation towards embryonic keratinocytes.     

Acantholytic variant of seborrheic keratosis

From among 524 histologic specimens of seborrheic keratosis (SK), 29 showed acantholysis, not related to pemphigus, Darier's disease, actinic keratosis or acantholytic squamous cell carcinoma. Acantholysis was found in 24 (23.3%) of the irritated type of SK, almost exclusively in the squamous cell nests showing dyskeratosis and spongiosis between and around squamous eddies or horn cysts. Clinically, 65.5% of the lesions were located on the face and scalp, 20.7% on the trunk and 13.8% on the limbs. It was speculated that dyskeratotic, degenerative changes of the keratinocytes together with spongiosis were responsible for the acantholysis.     

High expression level of homocitrulline is correlated with seborrheic keratosis and skin aging

BackgroudHomocitrulline (Hcit), is involved in the pathological processes of some diseases. However, the role and function of Hcit (CBL) in human skin remains largely obscure.ObjectiveTo investigate the correlation of the level of Hcit in seborrheic keratosis, skin aging, and its clinical significance.MethodsImmunohistochemistry was used to analyze the level of Hcit in skin lesions of seborrheic keratosis (SK), unaffected skin (distant 0.5 centimeters from SK lesion), and normal skin of healthy subjects in the control group. ELISA test was used to detect the serum level of CBL in SK patients and healthy subjects of different ages.ResultsHcit was mainly localized in the nucleus of epidermal cells. In healthy control skin, the expression of Hcit increased with age and showed a positive correlation with age (the correlation coefficient was 0.806, p = 0.0002). The expressional level of Hcit in SK lesions was higher than that in healthy control skin (Z = −3.703, p = 0.0002). The serum level of CBL in healthy subjects and in SK patients increased with age (the correlation coefficient were 0.5763, p = 0.0032; 0.682, p = 0.004. respectively). The serum level of CBL in SK patients was higher than that in healthy subjects (Z = −2.19, p = 0.030).Study limitationsThe small serum sample size in the study.ConclusionThe high expressional level of Hcit is correlated with seborrheic keratosis and skin aging. HCit may be one of the potential biomarkers of skin aging.     

Verruciform xanthoma-like phenomenon in seborrheic keratosis

Verruciform xanthoma is xanthomatous dermal infiltrate in a proliferating epidermal lesion and is an uncommon phenomenon. It has been reported in various neoplastic or inflammatory conditions. We report a 72-year-old man who had an asymptomatic 1-cm black nodule on his abdomen. Histopathology showed a typical acanthotic type of seborrheic keratosis characterized by basaloid keratinocyte proliferation and pseudohorn cysts. Many aggregated xanthomatized cells were seen in dermal papillae within the acanthotic epithelium. Papillomatosis, parakeratosis, and neutrophil infiltrates, the histologic features of typical verruciform xanthoma, were not seen. The foamy cells were positive for CD-68 and vimentin and negative for cytokeratin and S-100. No human papillomavirus DNA was found by nested polymerase chain reaction. The blood lipid profile was normal. The presence of verruciform xanthomatous change in seborrheic keratosis provides further evidence that verruciform xanthoma may be a reactive phenomenon occurring in common skin disorders.     

Extramammary Paget's disease mimicking acantholytic squamous cell carcinoma in situ: a case report

Background: Extramammary Paget's disease (EMPD) is an uncommon skin neoplasm characterized by Paget's cells with pale‐staining cytoplasm in the epidermis, and cases with distinguished acantholysis but lacking characteristic Paget's cells were rarely reported in the literature. Methods: An 80‐year‐old male with lesion on scrotum was screened histologically and immunohistologically for the diagnosis of his tumor. Results: Histological examination showed acanthosis with cellular atypia and focal acantholysis, consistent with acantholytic squamous cell carcinoma in situ (SCCIS). No characteristic Paget's cells were observed in low magnification. Immunohistochemical staining showed carcinoembryonic antigen (CEA), cytokeratin 7 (CK7) and cytokeratin 8 (CK8) to be strongly expressed in the nests and singly arranged large tumor cells, and the surrounding epidermis was positive for CK5/6 and negative for CEA. Sporadic periodic acid‐schiff (PAS)‐positive cells could be seen in some areas. Conclusions: These findings strongly indicated the diagnosis of EMPD mimicking acantholytic SCCIS. Du X, Yin X, Zhou N, Zhang G, Shi H, Cao S. Extramammary Paget's disease mimicking acantholytic squamous cell carcinoma in situ: a case report.     

Human Papillomavirus Deoxyribonucleic Acid may not be Detected in Non-genital Benign Papillomatous Skin Lesions by Polymerase Chain Reaction

Background:

Papillomatosis is a known histopathologic pattern usually seen in human papillomavirus (HPV) infection and verruca vulgaris is the typical example. This pattern is also detected in some other benign cutaneous lesions such as nevus sebaceous (NS), seborrheic keratosis (SK), trichilemmoma (TL) and inverted follicular keratosis (IFK). The association between papillomatous lesions and HPV infection is questionable.

Objective:

The objective of this study was to investigate the presence of HPV deoxyribonucleic acid (DNA) in non-genital benign papillomatous skin lesions (NS, SK, TL and IFK) by polymerase chain reaction (PCR).

Materials and Methods:

A total of 100 specimens of non-genital NS, SK, TL and IFK were retrieved from archives of Dermatopathology Department of Razi Hospital, between 2003 and 2010. The conventional PCR using consensus GP5+/GP6+ primer and hydroxymethylbilane synthase gene as inner control was performed.

Results:

PCR for HPV DNA revealed no positive results in any of 28 seborrheic keratosis (SK), 28 nevus sebaceous (NS), 28 inverted follicular keratosis (IFK) and 13 trichilemmoma (TL) studied specimens.

Conclusion:

Papillomatosis is usually a characteristic pattern of HPV infection. However, we found no association between HPV infection and non-genital benign papillomatous lesions.     

Apoptosis Identified by DNA Fragmentation in Epidermal Neoplasms

In the previous study, we demonstrated apoptotic cells in basal cell carcinomas by means of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Positive staining cells were present at the peripheries and centers of the nests. The number of positive cells increased in cases showing deep infiltration. We also stained other epidermal neoplasms using this modified TUNEL method. In squamous cell carcinomas, many positive cells were observed in poorly differentiated types, but only a few cells were stained in well-differentiated types. TUNEL positive cells were rare in Bowen's disease. No positive cells were seen in seborrheic keratosis or verruca vulgaris. Our studies showed that apoptotic cells were more common in rapid growth neoplasms than in slow growth neoplasms.     

脂溢性角化病96例和日光性角化病28例临床与病理分析

目的观察脂溢性角化病(SK)与日光性角化病(AK)的临床及病理差异。方法回顾性分析本科门诊2006年1月-2011年7月经病理确诊的96例SK和28例AK患者的临床及病理资料,对数据用Excel整理与分析。结果①SK好发于中老年人,而AK好发于老年人;②SK皮损好发于头面、躯干及四肢,而AK好发于头、面和颈等光暴露部位;③组织病理:SK以角化型和棘层肥厚型为主,而AK以原位癌型和萎缩型为主;④SK临床与组织病理的诊断符合率为70.83%,而AK临床与组织病理的诊断符合率仅为46.43%,临床上易将AK误诊为SK。结论 AK发病晚于SK,临床上AK误诊率高于SK,两者鉴别诊断主要依赖组织病理。     

The "intraepidermal epithelioma" revisited: immunohistochemical study of the borst-jadassohn phenomenon

The true nature of the so-called intraepidermal epithelioma of Borst-Jadassohn is poorly understood; whether this represents a distinct tumor or a morphological phenomenon [Borst-Jadassohn phenomenon (BJP)] shared by different entities has been debated. So far, no detailed immunohistochemical studies have been performed to address this issue. The aim of our study was to get further insight into the pathogenesis of the intraepidermal epithelioma of Borst-Jadassohn/BJP. Tumors showing the BJP [mainly clonal seborrheic keratoses (cSK) and clonal Bowen disease (cBD)] were studied and compared with typical (nonclonal) counterparts. Cell nests in cSK, cBD, hidroacanthoma simplex (HS), and porocarcinoma (PC) showed strong expression of epidermal growth factor-receptors (EGF-R), Ki-67, p63, and p53. Cell nests of clonal SK and HS (but not of clonal BD or PC) expressed keratin 5/6. The expression of E-cadherin and the number of CD1a+ Langerhans cells were reduced within the nests of all lesions, whereas melanocytes were increased in all of them. Keratins 7 and 19 were not expressed in any of the lesions. Tumors showing the BJP exhibit some immunohistochemical differences, suggesting that they represent separate entities. However, they all show strong expression of EGF-R within intraepidermal keratinocyte nests, suggesting that the epithelial growth factor pathway plays a role in the development of the BJP.     

Differentiation of hidroacanthoma simplex from clonal seborrheic keratosis--an immunohistochemical study

Hidroacanthoma simplex (HS) is an uncommon poroid neoplasm confined within the epidermis. The clinical features of HS are not distinctive and histopathologically HS may be confused with clonal seborrheic keratosis (CSK) if cystic or ductal structure is not present. The purpose of our study was to differentiate HS from CSK by the immunohistochemical expressions of various cytokeratins, CEA, CD1a, and S-100 protein, as well as by the degrees of deposition of melanins and glycogen. Four cases of HS and seven cases of CSK were included in the research. In contrast with CSK, HS showed a very low density of Langerhans cells (19.9 +/- 7.7 versus 3.1 +/- 1.0 CD1a (+) cells/mm, P = 0.027) and sparse melanin deposition in the nests. However, HS could not be set apart from CSK by the expressions of cytokeratins. The nests of both HS and CSK showed very similar patterns of cytokeratin expression and seemed to be mainly composed of basaloid cells with focal differentiation toward epidermal suprabasal cells.     

转化生长因子-α在脂溢性角化病皮损中的表达

目的　探讨转化生长因子 α(TGF α)与脂溢性角化病 (SK )发病的关系。方法　采用免疫组化法检测 3 0份SK皮损组织和 10份正常皮肤组织中TGF α的原位表达水平。结果　SK皮损组织中有TGF α的表达 ,其阳性表达程度与正常对照组比较差异有显著性。结论　SK皮损组织中TGF α异常高表达 ,提示TGF α可能参与了SK的增殖过程     

A comparative study of seborrheic keratoses and basal cell epitheliomas by complement immunofluorescence and electron microscopy

Eight cases of seborrheic keratosis (SK) and 7 cases of basal cell epithelioma (BCE) were studied comparatively by complement immunofluorescence using pemphigoid serum which was reactive not only to the basement membrane zone (BMZ) but also to the cell membrane or the intercellular space (CMICS) of basal cells in normal human epidermis. Positive immunofluorescence both at the BMZ and the CMICS of proliferating basaloid cells was observed in all cases of SK, whereas in BCE, immunofluorescence weaker than that in SK was observed only a the BMZ of tumor cell nests. These tumors were also examined by light and electron microscopy, and differences already described in the literature between SK and BCE were confirmed. These findings suggest that antigenic properties of the BMZ of the skin are affected by proliferating epithelial cells and that epithelial cells are involved in the formation of the BMZ.     

Detection of human papillomavirus DNA in seborrheic keratosis by polymerase chain reaction.

We searched for HPV DNA in 72 cases of seborrheic keratosis (nongenital SK 29, genital SK 43) using polymerase chain reaction. Amplification of HPV DNA was found in 24 (nongenital, 1; genital, 23). HPV DNA type 6 was present in 18 cases and type 11 in four and type 33 in two. Twenty-three (53%) cases of genital region SK and one (3%) case of nongenital region SK contained HPV DNA sequences. Histopathologically, the perinuclear vacuolization of epithelial cells, mitosis and dyskeratotic cells were more marked in HPV DNA-positive SK than those in negative SK (P < 0.01). We suppose HPV may play an important role in epidermal proliferation of SK in the genital region.