Strahleninduzierte kutane Hamartome bei einer Patientin mit Cowden-Syndrom Klinische Evidenz für Verlust der Heterozygotie

A 56-year-old woman had typical features of Cowden syndrome in the form of hamartomas involving the skin, lips, and oral mucosa. At the age of 48, a mastectomy was performed for adenocarcinoma with a regional metastasis, and X-ray treatment was applied to the left axilla. Subsequently the patient developed approximately 30 skin-colored nodules surrounding the irradiated axillary region within several months. Histopathological examination of one of these lesions showed characteristic features of sclerotic fibroma. The multiple radiation-induced fibrous hamartomas observed may be best explained by multiple events of loss of heterozygosity (LOH), because molecular studies in other patients with Cowden syndrome have shown that both benign and malignant tumors originate from LOH. The X-ray treatment would have induced LOH in many cells, giving rise to either homo- or hemizygosity for the Cowden mutation.     

Pacinian collagenoma: A distinct form of sclerotic fibroma

Sclerotic fibroma (storiform collagenoma) is a rare benign skin tumor. A solitary tumor, as well as multifocal lesions, are found either sporadically, or associated with Cowden syndrome. The tumor usually presents as clinically asymptomatic, slowly growing papule or nodule on the skin of the head, neck, and upper extremities. Microscopically the lesion is sharply demarcated, composed of hyalinized bands of collagen with low cellularity and a distinctive irregularly whorled or storiform pattern. We describe a case of a unique variant of this tumor in the scalp of a 33-year-old male. The tumor was microscopically composed of concentrically arranged collagen bundles with prevailing type III collagen, which resembled an enlarged Vater-Pacini corpuscle, with low density of CD34-positive and glucose transporter 1-negative spindle shaped cells. The specific microscopic appearance is suggestive of the term “Pacinian collagenoma” for this unique benign tumor.     

Expression of CD34 in sclerotic ("plywood") fibromas

CD34 antigen is expressed in normal human skin on endothelium, in spindle cells located around adnexal structures, and in a subset of interstitial cells in the reticular dermis. CD34 expression has also been identified in a number of fibrohistiocytic neoplasms, such as dermatofibrosarcoma protuberans and solitary fibrous tumors of soft tissue. CD34 expression has not previously been described in sclerotic, or "plywood" fibromas. Here presented are three lesions from three patients, in which histologic examination revealed a well-circumscribed dermal nodule composed of spindled cells with focal nuclear pseudo-inclusions. There was extensive fibrosis with hypocellular, storiform areas, characteristic of sclerotic fibroma. The spindled cells strongly expressed CD34, but not factor XIIIa or markers of melanocytic, neural, or muscular differentiation. A diagnosis of Cowden syndrome was considered in one of the cases. These cases provide evidence that CD34 expression can occur in sclerotic fibromas, either solitary or associated with Cowden syndrome. When diagnosing a sclerotic fibroma, one should comment in the report regarding the possibility of Cowden syndrome.     

Cutaneous solitary fibrous tumor: a report of 2 cases and review of the literature

Solitary fibrous tumor is an uncommon mesenchymal neoplasm that can arise in both pleural and extrapleural locations. Composed of spindled cells intimately admixed with collagen bundles arranged in a "patternless pattern," this heterogeneous tumor can mimic a variety of benign and malignant mesenchymal neoplasms. We present the histological and immunohistochemical findings of two primary cutaneous solitary fibrous tumors, discuss the differential diagnosis, and review the literature. Although solitary fibrous tumors in cutaneous and subcutaneous regions are extremely rare, it should be considered in the differential diagnosis of primary spindle cell neoplasms of the skin.     

Solitary circumscribed neuroma (palisaded encapsulated neuroma) of the oral mucosa

BACKGROUND: The solitary circumscribed neuroma or "Palisaded Encapsulated Neuroma" is an infrequent benign tumor of the skin of adults, often localised on the face, around the orifices. The involvement of the oral mucosa or of the vermilion border of the lips is rare.CASE REPORTS: In our 5 cases, a small painless and more or less protruding nodule had been present for years on the mucosa of the hard palate (50 year-old man, 43 year-old woman), the soft palate (63 year-old woman), the vermilion border of the lower lip (48 year-old woman), and the gingiva (26 year-old man). The non specific clinical aspect did not permit a correct diagnosis.DISCUSSION: Histologically, the solitary circumscribed neuroma is formed by a proliferation of Schwann cells arranged in interlacing bundles, featuring one or several well-limited nodules, sometimes surrounded by a thin capsule. At first sight, this aspect might sometimes mimic schwannoma or neurofibroma. The lesion is interspersed with a variable amount of axons. An association with neurofibromatosis or MEN syndrome type IIb has never been found. Even after incomplete excision the solitary circumscribed neuroma does not recur, a fact supporting a reactive rather than a neoplastic origin.     

Giant cell collagenoma: case report and review of the literature

BACKGROUND: Giant cell collagenoma (GCC) is a recently described cutaneous fibrous neoplasm that usually affects young to middle-aged adults. Despite its similar histological appearance with circumscribed storiform collagenoma, no association of GCC with Cowden's syndrome has been described so far. To the best of our knowledge only five cases of this rare fibrous tumor have been reported so far. METHODS: We report a case of a 79-year-old male patient presenting with a slow growing flesh-colored dome-shaped lesion in his left forearm, with a clinical diagnosis of fibroma. No stigma of Cowden's syndrome was depicted. RESULTS: The histological analysis showed a symmetrical and well-circumscribed flat-dome-shaped lesion covered by an atrophic overlying epidermis. The neoplasm was composed of hyalinized collagen bundles disposed in a whorled storiform pattern. Admixed with the collagen matrix, there were two distinct cell populations, one composed by spindle-shaped mononuclear cells, and the other composed by bizarre multinucleated giant cells. Immunohistochemical analysis showed positivity for vimentin and actin HHF35 in the mononucleated. The multinucleated cells only immunoexpressed vimentin. CONCLUSION: GCC is an unusual cutaneous fibrous tumor that should be differentiated from circumscribed storiform collagenoma, pleomorphic fibroma, regressive forms of dermatofibroma, and solitary myofibroma based on its histological features.     

Multiple Nuchal-Type Fibromas on the Scalp: A Case Report

Nuchal-type fibroma is a rare, benign, fibrous, tumor-like proliferation characterized by dense hypocellular bundles of collagen, with sparsely scattered fibroblasts, interspersed fat tissue, and entrapped nerve fibers. It usually develops in the posterior neck as a solitary, firm, poorly circumscribed, subcutaneous mass. Herein, we report about a 32-year-old man who presented with a 6-year history of multiple nodules on the scalp. Histopathological features were consistent with those of nuchal-type fibroma. The tumors were surgically excised.     

获得性指(趾)部纤维角化瘤12例

目的 探讨获得性指(趾)纤维角化瘤临床及病理特点.方法 对确诊为获得性指(趾)部纤维角化瘤患者的临床表现、组织病理特点和治疗方法及转归进行分析.结果 12例患者发病年龄17～64.5岁(39.75±17.69)岁,病程0.5 ～ 20年(4.83±5.77)年,男:女为1.4∶1.皮损表现为多形态,主要累及指、趾、甲沟,也可累及非肢端部位.皮损组织病理检查:表皮角化过度和棘层肥厚,表皮突增宽呈分枝状,皮损中心由成熟的胶原束、成纤维细胞和大量扩张毛细血管组成.其中大部分胶原束与表皮相垂直走行,为其特征性表现.结论 获得性指(趾)部纤维角化瘤是一种少见、原因不明的皮肤纤维组织良性肿瘤,多发于成年人指或趾,一般为单发,但也可发生于非肢端.采取手术或激光治疗,少有复发.     

Sclerotic (fibroma-like) lipoma: a distinctive lipoma variant with a predilection for the distal extremities

This report details the clinicopathologic and immunohistochemical findings identified in 21 cases of a fibrosclerotic variant of lipoma from acral sites that is frequently misdiagnosed as a fibromatous (nonlipogenic) process. The study includes 12 males and 9 females; aged 7 to 72 (mean and median, 39). The patients presented with solitary, mostly asymptomatic, masses that ranged from 0.6 to 2.2 (median, 1.2; mean, 1.3) cm and involved fingers (n=17), hands or wrists (n=3), and toes (n=1). Microscopically, the lesions were well-circumscribed nodules that showed very low to moderately low cellularity and consisted of cytologically bland spindled and stellate-shaped cells and a minor component of randomly dispersed adipocytes embedded in a collagenous to myxocollagenous stroma. Eight tumors were "fibroma-like" owing to their paucity of spindled cells, dense fibrosclerotic stroma, and inconspicuous vasculature. One tumor showed features of spindle cell/pleomorphic lipoma, whereas another demonstrated a vague onion skin-like arrangement of collagen reminiscent of sclerotic (storiform) fibroma. In all cases, the mitotic activity was negligible. Nonlipogenic tumor cells were immunoreactive for CD99 (6 of 6 cases), CD34 (6 of 8), S-100 protein (4 of 7), and smooth muscle actin (2 of 6). Follow-up data on 8 patients (range, 1 to 20 years; median, 9.5 years) revealed no recurrence in 6, but indicated the possibility of persistent tumor in the remaining 2 individuals after simple excision. Despite histological overlap in 1 case with the sclerotic fibroma, no patient displayed definitive clinical features of Cowden syndrome. Our study indicates that fibrosclerotic lipomas demonstrate a broader histological scope than what was initially described.     

Trichilemmomas show loss of PTEN in Cowden syndrome but only rarely in sporadic tumors

Background: Trichilemmoma (TL) can occur as a solitary sporadic lesion usually on the face or as multiple facial lesions almost invariably associated with Cowden syndrome (CS). CS is a multisystem disorder caused by a germline inactivating mutation in PTEN (10q23.31), a tumor suppressor gene. We sought to identify PTEN loss by immunohistochemistry (IHC) in sporadic and CS‐associated TL to determine whether IHC is a useful tool to assess an individual for CS. Methods: Six TL biopsies associated with CS and 33 biopsies without CS were retrieved. IHC for PTEN was performed. Results were scored as positive (reactivity in TL cells) or negative (no reactivity in TL cells); normal squamous epithelium and vascular endothelium served as internal positive controls. Results: Complete PTEN loss was noted in 5/6 (83%) CS‐associated TL and 1/33 (3%) sporadic (non‐CS) TL. Conclusion: Demonstration of complete PTEN loss in TL by IHC is strongly suggestive of association with CS, but retention of PTEN staining does not entirely exclude CS. Therefore, PTEN IHC in TLs may be helpful in screening TL for association with CS, but should be used in context with other established clinical criteria, and possibly germline PTEN genotyping to confirm a diagnosis of CS. Al‐Zaid T, Ditelberg JS, Prieto VG, Lev D, Luthra R, Davies MA, Diwan AH, Wang W‐L, Lazar AJ. Trichilemmomas show loss of PTEN in Cowden syndrome but only rarely in sporadic tumors.     

Cowden's syndrome: a clinical, immunological, and histopathological study

Background Cowden’s syndrome is a rare, autosomal dominant condition characterized by hamartomas of the gastrointestinal tract and cancer of the breast and thyroid. This study describes the clinical, immunological, and histopathological status of four Cowden’s syndrome cases from two different families. Methods Biopsies were taken from different skin, mucous membrane, and intestinal lesions in all patients. Blood samples from patients and their parents were also examined. Results Two brothers in the first family had more flexural distribution of papular and warty skin lesions as well as other manifestations of the syndrome, including recurrent pyogenic and fungal infections. Flow cytometric study revealed decreased total T and B‐cell percentages and abnormal helper : suppressor ratios in these patients. The other two patients from the second family showed the classical picture of the syndrome and normal immunological parameters. Histopathologically, most skin lesions of the face showed trichilemmomas, and all oral and some of the other skin lesions showed benign fibromas with giant cells (Cowden’s fibroma). Examination of intestinal biopsies revealed hamartomatous and hyperplastic polyps. Conclusions Some cases of Cowden’s syndrome may be associated with prominent flexural skin lesions, recurrent pyogenic and fungal skin infections, decreased total T and B‐cell counts, and an abnormal helper : suppressor ratio.     

Fibroma esclerótico con células gigantes multinucleadas

—Sclerotic fibroma is a benign neoplasm usually solitary (when it is multiple, it is part of the Cowden syndrome) whose right diagnosis is only established after histopathologic study. In 1998, a histological variant containing multinucleated giant cells has been described.We report a case of this new variant. It was a nodule, 1 cm in diameter, on a finger of a 35-year-old man.     

Multiple cutaneous fibrous histiocytomas in association with systemic lupus erythematosus

Cutaneous fibrous histiocytomas are usually regarded as superficial lesions and commonly known as dermatofibromas; however, unusual cases histologically showing fibrohistiocytic proliferation extending into the deeper dermis or subcutaneous tissues are occasionally experienced. Some authors propose this type as benign fibrous histiocytoma of the skin, distinct from dermatofibroma. We describe herein a case of systemic lupus erythematosus (SLE) who developed multiple nodules on the face, trunk and extremities. The nodule on the forehead did not present a typical clinical appearance of dermatofibroma, and histopathological examination showed fibrohistiocytic proliferation with a storiform pattern extending into the deep dermis and subcutaneous tissues. By contrast, histology of the nodule on the abdomen showed fibrohistiocytic proliferation confined to the dermis and compatible with dermatofibroma. Although multiple dermatofibromas are occasionally seen in patients with SLE, benign fibrous histiocytoma of the skin showing deeper invasion than dermatofibroma is rarely associated with SLE.     

Fibrous papule of the face. A study of five cases by electron microscopy

The stellate-shaped and multinucleated cells in fibrous papule of the face from five patients were studied by electron microscopy and found to be fibrohistiocytic cells.     

Skin abnormalities in individuals with macrocephaly: Cowden disease from a dermatologist's point of view

Cowden disease is a rare autosomal dominant disorder characterized by multiple hamartomas and (malignant) tumors affecting major organs including the breast, thyroid, endometrium, brain, skin and mucosa. Diagnostic criteria as formulated by the International Cowden Consortium serve as a guideline to clinically identify patients in which Cowden disease is suspected. However, the spectrum of abnormalities associated with PTEN mutations is very broad, such that the term PTEN hamartoma tumor syndrome (PTHS) is often used. The diagnostic criteria for Cowden disease do not always serve to reliably identify patients who fall within the PTHS spectrum. Therefore, it is important that clinicians are aware of features that should raise the suspicion of such a syndrome. To illustrate this point, we present three patients with clinical features of the PTEN hamartoma tumor syndrome spectrum. These patients have macrocephaly in common. Two of them meet the criteria for Cowden disease; one patient refused mutation analysis, while mutation analysis in the other patient revealed no PTEN mutation. The third patient does not meet the criteria for Cowden disease; however, genetic analysis showed a pathogenic mutation in the PTEN gene. Dermatologists regularly encounter the (muco-)cutaneous abnormalities that can be seen in PTEN hamartoma tumor syndrome. These findings combined with a (family) history of internal malignancy or a macrocephaly should raise the suspicion of PTHS, even in the absence of classical Cowden criteria.     

Light and electron microscopy of eruptive collagenoma

Connective tissue nevi may be multiple or solitary, sporadic or familial. Eruptive collagenoma is a variant of the acquired collagenomas characterized by multiple sclerotic papules with an acute onset. A 13-year-old girl reported that in the past year, small asymptomatic lesions began to appear in her skin, 30 lesions were seen in the trunk, 5 in the cervical region and 1 in the face. Light microscopy with hematoxylin and eosin staining showed sparse collagen fibers, with Weigert staining diminished elastic tissue was observed. Scanning electron microscopy of the dermis showed individualized collagen fibers forming waved compact masses and not bundles. Transmission electron microscopy also showed sparse and loose collagen fibers with different diameters in cross sections.     

Cowden综合征1例

患者女,19岁,口腔、面、四肢丘疹15年,腹痛2周。皮肤科情况:口腔黏膜、舌部、面部及四肢可见散在皮色角化性丘疹,部分呈疣状或乳头瘤样,面部为甚。胃肠镜检查:消化道多发性息肉。组织病理学检查:(胃窦黏膜)增生性息肉伴中度慢性炎症,HP(+);(舌部)鳞状上皮乳头状瘤;(右前臂)表皮角化过度,局部棘层及颗粒层增生。诊断:Cowden综合征。     

Focal dermal hypoplasia: ultrastructural abnormalities of the connective tissue

We followed over 10 years three girls with focal dermal hypoplasia syndrome. The histopathological changes demonstrated at the optical level an hypoplastic dermis with thin and scarce collagen bundles and a marked diminution of elastic fibers. Mature adipose tissue was found scattered within the papillary and reticular dermis. No alterations in the basal membrane were observed by immunocytochemical or ultrastructural techniques. Ultrastructurally, in the skin-affected areas, loosely arranged collagen bundles composed of few fibrils were seen scattered in the extracellular matrix. Scarce elastic fibers of normal morphology were also observed. Fibroblasts were smaller, oval-shaped, and diminished in number with a poorly developed cytoplasm. In these fibroblasts, the most conspicuous feature was a remarkable and irregular thickening of the nuclear fibrous lamina. Taking into account that a common link between all laminopaties may be a failure of stem cells to regenerate mesenchymal tissue, this failure would induce the dermal hypoplasia observed in our patients presenting Goltz syndrome.     

Multibranched acquired periungual fibrokeratomas with confounding histopathologic findings resembling papillomavirus infection: a report of two cases

Acquired periungual fibrokeratomas are benign fibrous tissue tumors and are considered as the topographical variant of acquired digital fibrokeratoma. They usually present as solitary tumors. In some instance, the entity may appear in multibranched fashion. The main histopathologic features consist of acanthosis, thick collagen bundles mainly oriented in a vertical axis forming a central core, and numerous proliferating fibroblasts. In this article, we present two cases of acquired multibranched periungual fibrokeratoma and depict their varying clinical features over time. Binucleation and perinuclear halos of keratinocytes mimicking human papillomavirus (HPV) infection were detected microscopically, but there was no reactivity with HPV immunostaining. In context, anti‐HPV immunostaining may be helpful in the differentiation of fibrokeratomas from HPV infection. On the other hand, it should be kept in mind that these histopathologic findings may be found in acral biopsies independent of viral effects.     

Giant aneurysmal benign fibrous histiocytoma (dermatofibroma)

Aneurysmal benign fibrous histiocytomas are variants of dermatofibromas. These benign blood‐filled lesions can mimic malignancies due to their rapid and recurrent growth. Our patient is a 42‐year‐old Caucasian female with a past medical history of morbid obesity, diabetes, and hypertension, who presented with a mass on her left shoulder for 5 years’ duration. The mass oozed occasionally and would appear to regress but then recur replaced with progressively larger masses. Upon inspection, the patient had a large pedunculated exophytic mass with vascularity. The mass was surgically removed under general anesthesia via wide local excision. Grossly, the excised skin was purple‐tinged with an underlying fungating solid mass measuring 8.5 cm. Serial sections revealed a hemorrhagic, spongy, and granular cut surface. Histologically, the epidermis was hyperplastic, with underlying hyaline collagen bundles. The remainder of the mass was chronically inflamed and composed of spindled histiocytes, hemosiderin‐laden macrophages, and blood‐filled spaces lacking an endothelial lining. There was focal pleomorphism but no significant atypia. Immunohistochemical stains were strongly positive for vimentin and negative for CD31, CD34, and desmin. The overall architecture and immunophenotype are consistent with the diagnosis of aneurysmal benign fibrous histiocytoma.