Bladder carcinoma with shadow cell differentiation: a case report with immunohistochemical analyses

A peculiar case of bladder carcinoma showing shadow cell differentiation (SCD) in a 72-year-old man is presented. The tumor histologically revealed high grade urothelial carcinoma (UC) and partially contained squamous component with a transition to shadow cell nests, similar to those seen in cutaneous pilomatricoma (PMX). Immunohistochemically, the modes of cell death in the component of SCD were identical to those in PMX. The present case as well as 10 cases of cutaneous PMX showed nuclear expression of beta-catenin, whereas 10 cases of bladder UC with squamous differentiation revealed membranous localization without nuclear expression. These results suggest that nuclear accumulation of beta-catenin may play an important role for SCD in the present case. SCD in extracutaneous tumor is extremely rare and, in the literature, the present case is the second one as for bladder carcinoma.     

E-cadherin promoter hypermethylation in preneoplastic and neoplastic skin lesions.

E-cadherin is a calcium-dependent, intercellular adhesion molecule that is specifically expressed in epithelial tissues and plays an important role in maintaining epithelial stability. E-cadherin is widely regarded as a prognostic marker in many types of human cancers. The inactivation of the E-cadherin gene is linked to increased potential for tumor invasiveness and distant metastasis. We previously demonstrated reduced expression of E-cadherin protein immunohistochemically in invasive squamous cell carcinomas of the skin as compared with adjacent normal skin. An epigenetic alteration in association with promoter hypermethylation is one important mechanism of gene silencing. In the present study, we analyze the E-cadherin gene promoter hypermethylation in preneoplastic and neoplastic skin lesions to determine whether epigenetic alteration of the E-cadherin gene also plays an important role in cutaneous squamous carcinogenesis. A total of 33 cases was examined for evidence of E-cadherin promoter hypermethylation, and these consist of nine cases of spongiotic dermatitis as nonneoplastic skin control, nine cases of actinic keratosis, eight cases of squamous cell carcinoma in situ, and seven cases of invasive squamous cell carcinoma. Promoter hypermethylation of the E-cadherin gene was detected in 6 of 7 cases (85%) of invasive squamous cell carcinoma, 4 of 8 cases (50%) of squamous cell carcinoma in situ, 4 of 9 cases (44%) of actinic keratosis, and 2 of 9 cases (22%) of nonneoplastic skin. We conclude that E-cadherin promoter hypermethylation occurs frequently and may represent an important mechanism of E-cadherin inactivation in cutaneous preneoplastic and neoplastic lesions. The frequencies of E-cadherin promoter hypermethylation appear to be correlated with more advanced stage of squamous carcinogenesis in skin.     

Analysis of promoter hypermethylation of death-associated protein kinase and p16 tumor suppressor genes in actinic keratoses and squamous cell carcinomas of the skin.

Death-associated protein kinase is a serine/threonine protein kinase implicated in promoting apoptosis and tumor suppression, whereas p16 is a tumor suppressor gene that inhibits cyclin-dependent kinase 4 and 6 activity and arrests the cell cycle in the G1 phase. Hypermethylation of death-associated protein kinase or p16 gene with resultant gene inactivation has been described in a wide variety of human cancers. Promoter methylation of the death-associated protein kinase and p16 gene has been found in about 55% and 30% cases of head and neck squamous cell carcinoma respectively but has not yet been analyzed in cutaneous premalignant and malignant lesions. A total of 33 cases were examined for evidence of death-associated protein kinase and p16 hypermethylation and these consist of 9 cases of spongiotic dermatitis as nonneoplastic skin control, 9 cases of actinic keratosis, 8 cases of squamous cell carcinoma in situ, and 7 cases of invasive squamous cell carcinoma. Death-associated protein kinase promoter methylation was detected in 1 case of squamous cell carcinoma in situ and 1 case of nonneoplastic skin control but none of the cases of invasive squamous cell carcinoma or actinic keratosis. P16 promoter methylation was detected in 1 case of invasive squamous cell carcinoma and 1 case of nonneoplastic skin control but none of the cases of squamous cell carcinoma in situ or actinic keratosis. Promoter hypermethylation of the death-associated protein kinase and p16 genes does not appear to play an important role in the development of cutaneous squamous cell carcinoma. The data thus suggest that the mechanisms of ultraviolet-induced cutaneous carcinomas differ from those involved in the development of head and neck squamous cell carcinoma, a malignant disease induced by tobacco and alcohol exposure.     

High-risk cutaneous squamous cell carcinoma of the head and neck

Nonmelanoma skin cancers (squamous cell and basal cell carcinomas) occur at an epidemic rate in many countries with the worldwide incidence increasing. The sun-exposed head and neck are the most frequent sites for these cancers to arise and in most patients diagnosed with a cutaneous squamous cell carcinoma, local treatment is usually curative. However, a subset is diagnosed with a high-risk cutaneous squamous cell carcinoma. High-risk factors include size (>2 cm), thickness/depth of invasion (>4 mm), recurrent lesions, the presence of perineural invasion, location near the parotid gland, and immunosuppression. These patients have a higher risk (>10-20%) of developing metastases to regional lymph nodes (often parotid nodes), and in some cases also of experiencing local morbidity (perineural invasion), based on unfavourable primary lesion and patient factors. Despite treatment, many patients developing metastatic cutaneous squamous cell carcinoma experience mortality and morbidity usually as a consequence of uncontrolled metastatic nodal disease. It is therefore important that clinicians treating nonmelanoma skin cancers have an understanding and awareness of these high-risk patients. The aim of this article is to discuss the factors that define a high-risk patient and to present some of the issues pertinent to their management.     

Radiation-induced laryngeal angiosarcoma after cervical tuberculosis and squamous cell carcinoma: case report and review of the literature

Primary laryngeal angiosarcoma (LA) is quite rare with only 13 cases reported in English literature to date. A case of LA after radiation therapy for tuberculosis and squamous cell carcinoma is reported. A 70-year-old woman had a history of radiation therapy for left cervical tuberculosis at the age of 28. At 60 years of age a squamous cell carcinoma of the larynx was found and chemotherapy and radiotherapy, consisting of a total dose of 68.4 Gy, were administered. At the age of 68, recurrent squamous cell carcinoma was suspected from several biopsies, and a total laryngectomy with right thyroidectomy was performed. The tumor cells formed vascular spaces and expressed some endothelial markers, such as CD34, CD31, and Ulex europaeus agglutinin I, but no epithelial markers, such as cytokeratins or epithelial membrane antigen. No residual squamous cell carcinoma was found. In the present case, it was suspected that irradiation to the larynx for cervical tuberculosis and squamous cell carcinoma induced angiosarcoma. The patient was still alive despite multiple skin and soft tissue metastasis 3 years and 6 months after the radical operation. Distinction of postirradiation angiosarcoma from pseudoangiosarcomatous carcinoma seems difficult but is important because irradiation is not effective and an initial radical surgery is the only effective treatment. Although irradiation is a common treatment for laryngeal squamous cell carcinoma, this is only the second case of radiation-induced LA in English literature.     

Fine‐needle aspiration cytology in the diagnosis of malignant proliferating trichilemmal tumor: Report of a case and review of the literature

Malignant proliferating trichilemmal tumor is a rare cutaneous neoplasm derived from the outer root sheath of the hair follicle. Fine‐needle aspiration cytology is being increasingly used in the investigation of primary and metastatic cutaneous tumors. However, there are few reports on the cytology of trichilemmal tumors in the literature. We describe the cytological features of this uncommon adnexal tumor presenting as a scalp mass in a 58‐year‐old woman. In view of its aggressive biological behavior, it is crucial for cytologists to be aware of this rare lesion and distinguish it from primary cutaneous squamous‐cell carcinoma. The differences on fine‐needle aspiration cytology can be subtle and pose problems in diagnosis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Pigmented spindle cell carcinoid tumour of the thymus with ectopic adrenocorticotropic hormone secretion: report of a rare variant and differential diagnosis of mediastinal spindle cell neoplasms

AIMS: A variety of histological variants of thymic carcinoid tumour have been described. A rare case of pigmented spindle cell carcinoid tumour of the thymus is documented and compared with the reported cases of thymic pigmented carcinoid tumour in the literature, with a discussion of the differential diagnosis of spindle cell tumours of the mediastinum. METHODS AND RESULTS: A thymic tumour with ectopic adrenocorticotropic hormone (ACTH) secretion was resected from a 24-year-old man suffering from Cushing's syndrome. Histological, immunohistochemical, and ultrastructural studies revealed an ACTH-producing spindle cell carcinoid tumour harbouring pigmented melanocytes. Among four thymic pigmented carcinoid tumours reported before, only one was similar to the present case by being also an ACTH-secreting pigmented spindle cell thymic carcinoid tumour. The clinicopathological features of this tumour distinguish it from a spindle cell thymoma, spindle cell thymic carcinoma, and other mediastinal spindle cell tumours. CONCLUSIONS: This case illustrates an extremely rare variant of thymic carcinoid tumour exhibiting a spindle cell morphology and harbouring pigmented melanocytes. Awareness of this histological variant is important in the differential diagnosis of spindle cell tumours of the mediastinum.     

Clinicopathologic features of cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma

The clinicopathologic features of 32 cutaneous squamous cell carcinomas of the head and neck in 12 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were examined to determine the frequency of clinically aggressive and histologically poorly differentiated carcinomas in this group of patients. Two thirds of the neoplasms were multiple and 56% were high grade (grade 3 or 4). One of the 12 patients had recurrent carcinoma, two patients had recurrent and metastatic disease, and two patients had metastatic tumor without recurrence. Two patients died of tumor, one patient is alive with extensive recurrent and metastatic disease, and one patient died of an uncertain type of carcinoma. An additional patient with squamous cell carcinoma of the face died of cutaneous squamous cell carcinoma that arose on the chest. This study shows that cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma are often high grade and have the potential for recurrence and metastasis.     

VCAM (CD-106) and ICAM (CD-54) adhesion molecules distinguish keratoacanthomas from cutaneous squamous cell carcinomas.

Keratoacanthomas are rapidly growing benign epithelial derived neoplasms that may evolve into squamous cell carcinomas, or represent a variant of squamous cell carcinoma. ICAM (CD-54) is a ligand for the cell adhesion receptor LFA-1, shown to be important in immune stimulation that is upgraded in inflammatory cutaneous disorders. VCAM (CD-106) is an adhesion molecule normally found in stimulated endothelium, that plays a critical role in the migration of leukocytes. We examined the immunohistochemical expression of ICAM (CD-54) and VCAM (CD-106) in a series of 50 evolving, fully developed, resolving keratoacanthoma and well-differentiated and poorly differentiated squamous cell carcinoma to evaluate the possible temporal and pathogenic relation of these immune recognition markers and epithelial derived tumors. ICAM (CD-54) showed an increase in expression in the fully developed keratoacanthoma and was absent in the evolving and resolved keratoacanthoma. In the squamous cell carcinomas, expression was focally observed in the well-differentiated squamous cell carcinomas with a dramatic increase seen in the poorly differentiated squamous cell carcinomas. Similarly, VCAM (CD-106) was expressed in the fully developed keratoacanthoma and was absent in the evolving and resolved keratoacanthoma. Moderate expression for VCAM (CD-106) was seen in the well-differentiated squamous cell carcinoma, and intense expression was seen in the fully developed keratoacanthoma and poorly differentiated squamous cell carcinoma. As a group, keratoacanthoma and squamous cell carcinoma are immunophenotypically distinct. There is a temporal related increase in expression of VCAM (CD-106) in conjunction with the evolution of keratoacanthoma. Increased expression of both markers is seen with squamous cell carcinoma dedifferentiation. Application of these markers might be an important adjunct in predicting the biologic behavior and pathogenesis of these lesions.     

Cutaneous papillary squamous cell carcinoma. Report of three new cases and review of the literature

Squamous cell carcinoma is one of the most common malignant cutaneous tumors. Several histological variants have been described; the papillary subtype is one of the most infrequent, with only four cases having being reported previously. We report three new cases of this unusual variant of cutaneous squamous cell carcinoma, review the literature and consider the main differential diagnoses. Polymerase chain reaction performed in our three cases did not demonstrate human papilloma virus infection.     

Basaloid squamous carcinoma of the larynx. A potential diagnostic pitfall

Basaloid squamous carcinoma is a rare variant of squamous cell carcinoma. It is frequently diagnosed at an advanced stage with metastases. Histologically, it is identical to basaloid carcinoma at other anatomical sites. Some authors suggest that it may be associated with second primary tumors. Others implicate the Epstein-Barr and human papilloma viruses. All reports but one warn of its aggressive biological behavior. Our case concerns a 52-year-old man who had a small lesion in his right cord. Biopsy of the lesion was performed twice, and conventional squamous cell carcinoma was diagnosed; the patient returned 2 months later with progressed metastatic disease. The patient underwent a laryngectomy and a complete clinical and immunohistochemical investigation. Basaloid squamous carcinoma is a totipotential neoplasm with a grave prognosis. It can be misdiagnosed; therefore, the authors would like to emphasize the significance of this condition in comparison to conventional squamous cell carcinoma, and we provide a review of the relevant recent literature.     

Epidermal growth factor receptor: a novel biomarker for aggressive head and neck cutaneous squamous cell carcinoma

There is currently no prognostic tool that reliably predicts the risk of metastasis in cutaneous squamous cell carcinoma, most of which occur in the head and neck region. Epidermal growth factor receptor has received much interest in recent years with the advent of epidermal growth factor receptor-targeted molecular therapy in clinical oncology. We investigate the role of epidermal growth factor receptor as a biomarker for head and neck cutaneous squamous cell carcinoma. Using immunohistochemistry and fluorescence in situ hybridization, we assessed the epidermal growth factor receptor protein expression and gene copy in 3 groups of head and neck cutaneous squamous cell carcinoma: primary lesions not associated with metastasis (P), primary lesions associated with subsequent metastasis (PM), and metastatic nodal disease (M). Epidermal growth factor receptor overexpression was detected in 36% and 79% of P and PM cases, respectively. Epidermal growth factor receptor overexpression was significantly associated with PM (P = .03) and was found to be an independent prognostic factor for metastasis on multivariate analysis (P = .05). However, epidermal growth factor receptor overexpression was only maintained in 47% of cases in the M group. None of the 27 cases that overexpressed the epidermal growth factor receptor protein showed gene amplification: the results were uninterpretable in 2, and polysomy and balanced disomy were detected in 5 and 20 cases, respectively. These observations may have important prognostic and therapeutic implications for head and neck cutaneous squamous cell carcinoma.     

Primary squamous cell carcinoma of the colon arising in a villous adenoma

The first case of pure squamous cell carcinoma arising in a villous adenoma of the cecum is reported, and the literature of squamous cell carcinoma of the colon is reviewed. The possible origin of this neoplasm in adenomas of the colon, similar to that of adenocarcinoma, is discussed, and the site distributions of adenocarcinoma and squamous cell carcinoma are compared. The distribution of primary colonic squamous cell carcinoma is found to be predominantly right-sided in comparison to adenocarcinoma (p less than 0.05). Although this result does not preclude adenomas as the origin of most squamous cell carcinomas, it suggests the influence of as yet unknown site-asymmetric factors that are different from those for adenocarcinoma.     

Signet-ring squamous cell carcinoma

Among carcinomas, signet-ring morphologic characteristics have been regarded as pathognomonic of adenocarcinoma. This report presents the case of a poorly differentiated cutaneous squamous cell carcinoma with a monodispersed, invasive signet-ring component. Kreyberg stains had negative results for mucin. Immunohistochemical analysis demonstrated that concentric rings in the signet-ring cells were composed of keratin. To the best of the authors' knowledge, this is the first report of signet-ring squamous cell carcinoma. Another feature that bears emphasis is that this squamous cell carcinoma led to the death of the patient, even though it originated in a field of actinic keratosis.     

Follicular squamous cell carcinoma is an under-recognised common skin tumour

Current thinking assumes most cutaneous squamous cell carcinoma arise from the surface epidermis. Uncommon pilar and tricholemmal carcinomas are well recognised and recently authors have drawn attention to uncommon squamous cell carcinoma with predominant follicular infundibular differentiation. In contrast we propose that follicular (infundibular-tricholemmal) squamous cell carcinoma is exceedingly common and can be defined as follows: cytologically malignant tumour, abrupt connections to the epidermis (at follicular infundibula), infundibular and/or tricholemmal differentiation and lacking co-existent Bowen's disease or distinctive clinical-pathological features of keratoacanthoma. Recognition that many cutaneous squamous cell carcinoma are of follicular origin has major implications for differential diagnosis, staging, prognosis, management and future research.     

Pigmented oral squamous cell carcinoma: a case report and brief review of the literature

Melanin impregnation in squamous cell carcinoma (SCC) is an uncommon histological finding. Rare nonmelanocytic entities were previously described as having melanocyte colonization. A 57-year-old Brazilian woman was referred with a pigmented lesion in the lower lip and alveolar ridge with a prior clinical diagnosis of melanoma. The incisional biopsy of the tumor revealed an SCC with strong colonization of melanocytes in the stroma. The authors report a case of an unusual SCC variant and a brief review of the literature.     

Metalloproteinase-2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas.

Matrix metalloproteinases compose a family of enzymes involved in degradation of the extracellular matrix. Tumor cells must penetrate the basement membrane and traverse the extracellular matrix in order to invade surrounding structures and metastasize to distant sites. Gelatinases, particularly gelatinase A (matrix metalloproteinase-2), demonstrate degradative activity against components of the basement membrane and may be involved in the progression of in situ squamous cell carcinoma lesions. Matrix metalloproteinase-2 overexpression has been correlated with tumor invasiveness and metastasis in a wide variety of cancer types, including squamous cell carcinoma arising on mucous membranes. However, correlation between matrix metalloproteinase-2 overexpression and the spread and prognosis of cutaneous squamous cell carcinoma has not been characterized in the literature at present. In this study, we used immunohistochemical techniques to examine the expression of matrix metalloproteinase-2 in 10 actinic keratosis, 15 in situ, 13 invasive, 13 primary (with documented metastatic disease), 11 metastatic, and 8 recurrent squamous cell carcinoma cases. We found that while the average staining intensity (scale 0-3+, 3+ being strongest) of actinic keratosis and in situ lesions was not statistically significant (0.87-1.3 and 0.75-1.4, respectively), the average staining intensity of invasive squamous cell carcinomas (1.6-2.5) was significantly greater than that of actinic keratosis and in situ lesions. Likewise, while the average staining intensity of primary squamous cell carcinomas and metastatic squamous cell carcinomas was not found to be statistically significant (3.1-3.5 and 3.1-3.8, respectively), the average staining intensity of these lesions was significantly higher than that of invasive lesions. We also found that the intensity of matrix metalloproteinase-2 staining correlates with cellular atypia, inflammation, neovascularization, and the invasive tumor front, as well as tumor aggressiveness, and may play a role in the pathogenesis, invasion, and metastasis of cutaneous squamous cell carcinoma.     

人类疱疹病毒8型的K1基因亚型与鳞状细胞癌不同发病部位的相关性研究

目的 了解鳞癌组织中人类疱疹病毒8型(HHV-8)感染情况,探讨感染HHV-8 K1基因亚型与鳞癌发病部位的关系.方法 对40例皮肤鳞癌、40例食管鳞癌石蜡包埋组织进行HHV-8K1基因的DNA抽提、扩增、双向测序,使用Lagergene软件、CLUSTAL W软件和PHYLIP软件包对测序结果进行系统发生学分析,从而...     

Could EMA and cytokeratin 7 be useful in distinguishing tricholemmal carcinoma from clear-cell squamous cell carcinoma? A case series from our department and a brief review of the literature

Tricholemmal carcinoma is a malignant cutaneous adnexal tumor showing outer root sheath differentiation, thought to be the malignant counterpart of trichilemmoma. Although the real existence of tricholemmal carcinoma continues to be a matter of debate, it has been introduced in the recently published 4th edition of World Health Organization classification of skin tumors. Herein, we evaluated whether immunohistochemistry (EMA, CK7, CK5/14, p63, p16, and Ber-EP4) supports tricholemmal carcinoma as a separate entity and whether it could be useful in this differential diagnosis. A total of 9 cases, 3 tricholemmal carcinomas and 6 clear-cell squamous cell carcinomas were evaluated on the basis of histological criteria suggested by the WHO. In our opinion, although these results need to be validated in larger series, they support tricholemmal carcinoma as a separate entity and suggest an immunohistochemical profile (clear-cell squamous cell carcinomas: EMA diffusely positive, CK7 negative; tricholemmal carcinoma: EMA negative, CK7 patchy or moderately positive) that could be useful for this differential diagnosis.     

The presence of stage II melanosomes (premelanosomes) in neoplasms other than melanomas

Aside from melanomas, other nonmelanocytic pigmented tumors synthesize melanin or contain benign passenger melanocytes. While Stage IV melanosomes (mature melanosomes) occur in neoplasms which synthesize melanin as well as in those with benign companion melanocytes, Stage II melanosomes (premelanosomes), which are found in melanocytes and cells of pigmented nonmelanocytic tumors of neural crest origin, are considered the morphologic hallmark of in vivo melanin synthesis. To test this widely held concept, we studied the ultrastructure of representative malignant melanomas and other pigmented tumors (pigmented variants of the nevocellular nevus, squamous cell carcinoma, schwannoma, basal cell carcinoma, and seborrheic keratosis). Discrete intracytoplasmic Stage II melanosomes were noted in neoplastic cells of tumors of neural crest origin (melanoma, schwannoma, and nevocellular nevus), which are widely believed to synthesize melanin. In addition, they were also detected in neoplastic epithelial cells of a squamous cell carcinoma, basal cell carcinoma, and seborrheic keratosis. In these epithelial tumors, a spectrum of melanosomes from Stage II through Stage IV were presumably acquired from nonneoplastic companion melanocytes, which were an integral part of the tumor. Because squamous epithelium has not been shown to synthesize melanin, this study suggests that the finding of intracytoplasmic Stage II melanosomes does not necessarily imply melanin synthesis. When accompanied by melanocytes, epithelial and perhaps other tumors may contain ingested Stage II melanosomes.