An atypical, painful foot ulcer.

To the Editor: We have read with great interest the articles of Kazakov et al1 and Wilk et al2 on cutaneous adenolipoma, which were published in recent issues of the American Journal of Dermatopathology. To our knowledge, 8 previous well-documented cases of spindle cell lipoma combined with eccrine or apocrine components in the form of cutaneous spindle cell adenolipoma (SCAL) were reported so far in the literature.1,2 Recently, we had the opportunity to observe one similar case. SCAL can present diagnostic challenges for the unwary pathologists because of its rarity, unusual location, ill-defined border, and resemblance to other cutaneous lesions, both benign and malignant. Its true histogenesis is also controversial. A 35-year-old woman presented with a single soft polypoid skin nodule on the left arm for 4 months. It was asymptomatic, nontender, and slowly growing nodule. The initial clinical impression was neurofibroma, skin tag, or lipoma, and the lesion was surgically excised. Although the lesion was incompletely excised, there was no evidence of recurrence after 3-month follow-up. Macroscopically, the mass was soft polypoid skin nodule with intact skin surface. It measured 2.1 × 1.7 × 0.8 cm. The cut surface showed yellow tan to gray white solid ill-defined mass occupying the dermis and underlying subcutis. Microscopically, the lesion had an ill-defined low-power growth pattern. The bulk of the lesion was centered in the deep reticular dermis with irregular extension of the fibromyxoid mesenchymal stroma into the overlying superficial dermis and into the lobules of the underlying subcutaneous fat (Figs. 1A, B). Irregularly separated and dilated eccrine sweat glands and ducts were seen intermingled with the fibromyxoid spindle cell stroma (Figs. 1A–C). The stromal component was dominated by myxoid spindle cell mesenchymal proliferation admixed with mature adipocytes, ropy collagen strips, and scattered inflammatory cells, mainly mast and plasma cells (Fig. 1C). The spindle cells were bland, and no atypia or increased mitotic activity was seen. No prominent vascular proliferation or lipoblasts were seen. The epithelial component consisted of ordinary eccrine glands and ducts alternating with dilated and irregular ducts completely incorporated within the lipomatous component (Fig. 1C). The lining epithelium had the characteristic 2-layered cells encircled by intact basement membrane and underlying myoepithelial basal cells. The epithelium in the dilated ducts was flattened. No evidence of squamous metaplasia or hyperplasia was seen. Immunohistochemistry study for CD34, S-100 protein, smooth muscle actin (SMA), desmin, cytokeratin, factor XIIIa, and Ki67 was performed. The neoplastic spindle cells were positive for CD34 but negative for S-100 protein, cytokeratin, SMA, desmin, and factor XIIIa (Fig. 1D). The adipocytes were positive for S-100 protein (Fig. 1D). Ki67 index was very low in the spindle cells.FIGURE 1: A, The bulk of the fibromyxoid lesion is centered in the deep reticular dermis with irregular infiltration into the overlying superficial dermis. The epidermis and papillary dermis are uninvolved [hematoxylin and eosin (H&E), original magnification ×20]. B, The mixed myxoid adipocytic stromal and glandular components dissect through the collagen fibers of the deep dermis and extend into the lobules of the subcutaneous tissue (H&E, original magnification ×20). C, The lesion is composed of mixed fibromyxoid mesenchymal stroma and epithelial glandular structures. The predominantly myxoid stroma is admixed with adipocytic and fibrocollagenous tissue with ropy collagen strips. The glandular component consists of banal eccrine glands and ducts. Some are irregularly dilated ducts with flattened epithelium (H&E, original magnification ×200). D, CD34 immunomarker shows positive spindle cells (CD34; Dako, Glostrup, Denmark, ×400). Inset shows the S-100 protein–positive mature adipocytes and the negative spindle cells (S-100 protein, Dako, ×400).The first 9 cases of cutaneous adenolipoma described in the literature were by Hitchcock et al,3 who proposed the term “adenolipoma.” So far, approximately 43 cases have been reported in the English literature either as single case or series.1–5 Approximately, 26 cases of skin spindle cell lipoma have been reported in the literature.5 In contrast, to conventional deep spindle cell lipomas, the cutaneous variants are more common in women, have a wider anatomic distribution, are ill defined, and usually measure less than 2.5 cm.5 Cutaneous SCAL is rare. Kazakov et al1 reported 1 case of SCAL in their series study. Wilk et al2 reported 7 cases of cutaneous SCAL. Two were intradermal, 2 subcutaneous, and 3 involved the dermis and subcutis. To our knowledge, our case represents the ninth example of cutaneous SCAL. By definition, skin SCAL comprises both mesenchymal and epithelial components.1,2 The mesenchymal neoplastic part is composed of infiltrating fibromyxoid spindle cell stroma.1,2 The epithelial component is a constant finding and consists of widely spaced benign glandular acini and ducts mostly of eccrine and rarely apocrine units.1,2 Variation in the cytoarchitectural morphology, for example, cystic dilation, squamous metaplasia, and hyperplasia, could occur.1,2 The adenoid component should be incorporated within the tumor and not merely at the periphery of the tumor.3 The 2 components are usually present in a mixed pattern that could be confused with other lesions. The myxoid spindle cell stroma could be mimicked by neurofibroma, schwannoma, leiomyoma, nodular fasciitis, and dermatofibroma. The spindle cells in SCAL are CD34 positive but negative for S-100 protein, SMA, desmin, and factor XIIIa, which rule out these mimickers.5,6 The mixed growth pattern could be confused with benign eccrine/apocrine mixed tumor and hamartoma, for example, apocrine angiomatous hamartoma.1,3 Apocrine angiomatous hamartoma is a congenital lesion and shows predominance of vascular and eccrine components.2,3 Mixed tumors have more cellular and complex epithelial component with variable stromal components commonly chondroid. Epithelial mimickers might include primary adnexal malignancies and secondary carcinoma metastasis. Attention to the banal features of the glandular structures in SCAL should rule out this possibility. Mesenchymal mimickers could include atypical lipomatous tumor/well-differentiated liposarcoma, myxoid liposarcoma, and dermatofibrosarcoma. Lipoblasts and the chicken wire vascular proliferation are absent in SCAL. The neoplastic cells of both dermatofibrosarcoma and spindle cell lipoma are CD34 positive.6 However, dermatofibrosarcoma shows minimal disruption or expansion of the dermis, is more cellular with cytologic atypia, and shows more prominent mitotic activity.6 The true histogenesis of dermal SCAL and cutaneous adenolipomas in general is still controversial. Dermal adenolipoma is considered by most authors as a distinct cutaneous variant of benign superficial lipomas.1,3 Because spindle cell lipomas differentiate into mature adipocytes, spindle cells, and mucinous stroma, and the fact that many adnexal tumors and mixed tumor develop adipocytic metaplasia, some consider them hamartomas.2 Few authors do not consider adenolipoma as a specific entity because the adenoid components are merely entrapped and carried over elements.2 Some prefer the term perisudoral lipoma because these lipomas arise from the adipose tissue pad around the eccrine glands and the glandular component does not show proliferation.4 Cytogenetics studies and new immunomarkers might help differentiate cutaneous adenolipomas from other mimickers and confirm their neoplastic adipocytic origin.2,6 Adenolipomas are benign lesions. The treatment of choice is complete excision with no risk of recurrence.1–3 Even with incomplete excision, the risk of recurrence is low.1,2,5 In conclusion, dermal SCAL is best regarded as a rare variant of skin adenolipomas. Apart from its rarity and controversial histogenesis, the importance of SCAL is that it can be confused with other look-alike cutaneous lesions. Awareness of the existence of this entity and attention to certain morphologic and immunohistochemical features should help resolve this difficulty.

Introduction: High-intensity focused ultrasound (HIFU) and radiofrequency (RF) are used for non-invasive skin tightening. Neocollagenesis and neoelastogenesis have been reported to have a mechanism of controlled thermal injury. Objective: To compare neocollagenesis and neoelastogenesis in each layer of the dermis after each session of HIFU and monopolar RF. Methods: We analyzed the area fraction of collagen and elastic fibers using the Masson's Trichrome and Victoria blue special stains, respectively, before and after 2 months of treatments. Histometric analyses were performed in each layer of the dermis, including the papillary dermis, and upper, mid, and deep reticular dermis. Results: Monopolar RF led to neocollagenesis in the papillary dermis, and upper, mid, and deep reticular dermis, and neoelastogenesis in the papillary dermis, and upper and mid reticular dermis. HIFU led to neocollagenesis in the mid and deep reticular dermis and neoelastogenesis in the deep reticular dermis. Among these treatment methods, HIFU showed the highest level of neocollagenesis and neoelastogenesis in the deep reticular dermis. Conclusions: HIFU affects deep tissues and impacts focal regions. Monopolar RF also affects deep tissues, but impacts diffuse regions. We believe these data provide further insight into effective skin tightening.

Twelve cases of a unique plexiform melanocytic naevus that we have termed plexiform spindle cell naevus are reported. The lesions affected young individuals (mean age 22.5 years) of both sexes and were most frequently located on the shoulders and back. The lesions clinically were slightly raised and blue or darkly pigmented, suggesting blue naevus. Histologically these tumours had a symmetrical wedge-shaped configuration, as seen in typical Spitz naevus, with the apex directed toward the deep reticular dermis or subcutis. The pigmented spindle cells were disposed in fascicles in association with neurovascular bundles and adnexal structures, imparting a plexiform architecture to the lesion. The predominant cell type consisted of spindle cells containing a granular melanin and elongated nuclei. Low-grade cellular atypia was commonly noted. Varying numbers of epithelioid cells were observed in most of the cases. In two cases studied, the naevus cells showed S-100 protein and HMB-45 immunoreactivity. The differential diagnosis of plexiform spindle cell naevus includes malignant melanoma, and spindle and epithelioid cell (Spitz) naevus, blue naevus and combined naevus. Plexiform spindle cell naevus is a distinctive type of pigmented spindle naevus distinguished from the above entities by its striking plexiform architecture, predominance of melanin-containing spindle cells and lack of significant cellular atypia.

<h3>REPORT OF A CASE</h3> A 66-year-old white woman with type II diabetes mellitus requiring insulin and secondary nephrotic syndrome was found to have noncaseating granulomas, consistent with sarcoidosis, on a bone marrow biopsy specimen obtained for an evaluation for anemia. Corticosteroids were subsequently prescribed. Laboratory studies performed at that time disclosed the following values: serum urea nitrogen, 10.7 mmol/L (30 mg/dL), and creatinine, 92 μmol/L (1.1 mg/dL). Several months after corticosteroid therapy commenced, the patient noted tender nodules on her lower extremities. She was not receiving anticoagulants, did not increase her intake of calcium or phosphate, and was never hypercalcemic. She presented with firm, indurated, painful, subcutaneous nodules and plaques bilaterally on her calves and thighs with surrounding livedoid erythema. An incisional biopsy specimen was remarkable for abundant calcification in the deep reticular dermis and septae of the panniculus without vascular involvement or inflammatory response (<b>Figure 1</b>). The von Kossa

Matched Skin and Sentinel Lymph Node Samples of Melanoma Patients Reveal Exclusive Migration of Mature Dendritic Cells

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma comprising 5-10 percent of all soft tissue sarcomas [[1]]. MPNST frequently develops in young adults with preexisting plexiform neurofibroma in the majority of neurofibromatosis type 1 (NF-1) patients, accompanied by a prominent change in size and pain [[1]]. Most NF-1 shows benign growth, but in some people, a malignancy such as MPNST occurs. MPNST related to NF-1 has shown a highly aggressive pattern and a poor prognosis characterized by a high recurrence and metastasis rate, even after radical surgery [[1]].

Angiomyomatous hamartoma (AMH) is a rare benign lesion, which occurs almost exclusively in the inguinal lymph nodes. We herein report a case of a female elder who presented with a long-standing inguinal mass. Microscopically, the mass showed a zonal distribution, characterized by thick-walled muscular vessels, fibrosis, and calcification in the hilum and proliferating spindle cells around thin-walled vessels and plexiform vessel tangles at the periphery. The spindle cells show positive immunoreactivity of smooth muscle actin and CD34 with a heterogeneous expression of desmin and CD44. Although the pathogenesis of AMH remains uncertain, the histological features and immunohistochemical findings of this case imply a disordered or exuberant angiogenic process.

Metastatic Epithelioid Hemangioendothelioma of the Penis Managed With Surgery and Interferon-α

Morphea (localized scleroderma) is a disease of unknown etiology, presenting as circumscribed areas of indurated skin. Histologically, most cases of morphea feature thickened collagen bundles in the deep reticular dermis, sometimes also extending into the superficial dermis or into the subcutis. We present six cases of morphea in which typical histologic features were restricted to the superficial dermis and contrast these with 27 additional biopsies of conventional morphea seen during the same time period. Sections were stained for elastic fibers, and dermal dendritic cells were labeled with antibodies to CD34 and Factor XIIIa. All six cases showed thickened collagen bundles restricted to the superficial dermis, sparing the deep dermis and without associated evidence of lichen sclerosus et atrophicus (LSA). Dermal elastic fibers were not appreciably decreased in number. There was loss of CD34-positive dermal spindle cells in each of our six superficial examples of morphea, which was restricted to the area of altered collagen in four of the six cases. This report highlights the distinctly uncommon phenomenon of morphea presenting solely as alteration of the superficial reticular dermis, without features of LSA. The selective loss of CD34-labeled spindle cells may provide information regarding the role of these putative immune accessory cells in morphea. Recognition of this manifestation of morphea may be helpful diagnostically.

Malignant gastrointestinal neuroectodermal tumour in soft tissue

Kaposi sarcoma (KS), the most common AIDS-associated malignancy, is a multifocal tumor characterized by deregulated angiogenesis, proliferation of spindle cells, and extravasation of inflammatory cells and erythrocytes. Kaposi sarcoma-associated herpesvirus (KSHV; also human herpesvirus-8) is implicated in all clinical forms of KS. Endothelial cells (EC) harbor the KSHV genome in vivo, are permissive for virus infection in vitro, and are thought to be the precursors of KS spindle cells. Spindle cells are rare in early patch-stage KS lesions but become the predominant cell type in later plaque- and nodular-stage lesions. Alterations in endothelial/spindle cell physiology that promote proliferation and survival are thus thought to be important in disease progression and may represent potential therapeutic targets. KSHV encodes genes that stimulate cellular proliferation and migration, prevent apoptosis, and counter the host immune response. The combined effect of these genes is thought to drive the proliferation and survival of infected spindle cells and influence the lesional microenvironment. Large-scale gene expression analyses have revealed that KSHV infection also induces dramatic reprogramming of the EC transcriptome. These changes in cellular gene expression likely contribute to the development of the KS lesion. In addition to KS, KSHV is also present in B cell neoplasias including primary effusion lymphoma and multicentric Castleman disease. A combination of virus and virus-induced host factors are similarly thought to contribute to establishment and progression of these malignancies. A number of lymphocyte- and EC-based systems have been developed that afford some insight into the means by which KSHV contributes to malignant transformation of host cells. Whereas KSHV is well maintained in PEL cells cultured in vitro, explanted spindle cells rapidly lose the viral episome. Thus, endothelial cell-based systems for studying KSHV gene expression and function, as well as the effect of infection on host cell physiology, have required in vitro infection of primary or life-extended EC. This chapter includes a review of these in vitro cell culture systems, acknowledging their strengths and weaknesses and putting into perspective how each has contributed to our understanding of the complex KS lesional environment. In addition, we present a model of KS lesion progression based on findings culled from these models as well as recent clinical advances in KS chemotherapy. Thus this unifying model describes our current understanding of KS pathogenesis by drawing together multiple theories of KS progression that by themselves cannot account for the complexities of tumor development.

Drug name cyclosporine: Sandimmune A 58-year-old white woman presented with a 7-month history of indurated hyperpigmented plaques on her upper back, chest, abdomen, and arms. On the forearms and shins, associated with the induration, there was a waxy and shiny appearance. The lesions affected the dorsal aspect of both hands and feet, but spared the fingers and toes ( Fig. 1). Gradually, as her skin became more indurated, she developed flexural contractures, limiting her range of movement and impairing her daily physical activities. She denied other systemic symptoms. Figure 1. Bilateral legs with symmetric, firm, indurated plaques with a waxy and shiny appearance Download figure to PowerPoint She was empirically begun on prednisone, 20 mg daily, with a presumptive diagnosis of eosinophilic fasciitis; however, she did not respond to this therapy. At this point, laboratory examination revealed a normal complete blood count, and negative antinuclear antibodies and rheumatoid factor. The biopsy specimen showed a sparse perivascular lymphocytic infiltrate without eosinophils. The deep reticular dermis was thickened, and edematous, homogenized, horizontally oriented collagen bundles extended down fibrous septa into the fat. The underlying fascia was massively thickened and sclerotic with focal lymphoplasmacytic inflammatory infiltrate extending to the muscle ( Figs 2 and 3). Figure 2. Biopsy specimen showing horizontally oriented homogenized collagen bundles replacing subcutaneous septa (hematoxylin and eosin, ×10) Download figure to PowerPoint Figure 3. Biopsy specimen showing markedly thickened fascia with focal inflammatory infiltrate extending to the underlying muscle (hematoxylin and eosin, ×10) Download figure to PowerPoint The patient then received a course of pulsed methylprednisolone, 1 g daily, for 5 days, and was started simultaneously on cyclosporine, 150 mg, twice a day. Within 3 weeks, she had significant reduction of the skin induration as well as improved range of motion of her joints.

To the Editor: In 2014, superficial CD34-positive fibroblastic tumor (SCPFT), a mesenchymal neoplasm with intermediate malignancy, was identified by Carter et al.1 As an emerging novel disease entity, SCPFT is under-recognized in the field of dermatology.2 In this article, we present a case of SCPFT and a literature review. A 51-year-old woman presented with a 2-year history of a painful skin-colored subcutaneous tumor measuring 15 mm in diameter on the left thigh (Fig. 1). Skin biopsy revealed an infiltrative tumor composed of ovoid to spindled cells in a fascicular pattern, located in the deep dermis (Fig. 2). The tumor cells displayed granular cytoplasm and nuclear pleomorphism with bizarre, hyperchromatic nuclei, and intranuclear pseudoinclusions (Figs. 3A–D). Mitotic activity was scant, and atypical mitotic figures were not observed. Occasional multinucleated or lipidized tumor cells were identified, and necrosis was not observed. In terms of immunohistochemistry, the tumor cells were strongly positive for CD34 and focal aberrant expression of AE1/AE3 (Figs. 4A, B), focally positive for CD10, and negative for smooth muscle actin and S-100 protein. A diagnosis of SCPFT was established, and marginal excision of the residual tumor was performed. No local recurrence or distant metastasis occurred during the 4 years of follow-up.FIGURE 1.: A skin-colored subcutaneous tumor, about 15 mm in diameter, on the left thigh.FIGURE 2.: A relatively well-circumscribed tumor involving the deep dermis and extending into the superficial subcutis [hematoxylin and eosin (H&E) staining, ×10].FIGURE 3.: A, fascicles of ovoid to spindled tumor cells (H&E staining, ×100). B, Tumor cells show nuclear pleomorphism, with enlarged, bizarre, hyperchromatic nuclei (H&E staining, ×400). C, Tumor cells with abundant granular cytoplasm (H&E staining, ×400). D, Intranuclear pseudoinclusion (arrow) (H&E staining, ×400).FIGURE 4.: A, Diffuse and strong expression of CD34 (original magnification ×100). B, Focal aberrant expression of AE1/AE3 (original magnification ×100).Because SCPFT was first identified in 2014,1 only 38 cases have been reported in English-language literature2–10 (Table 1). In these 38 cases plus our patient, SCPFT usually occurred in young- to middle-aged adults (mean age, 37.7 years) with a slight male predilection (M:F 1.79:1). It presented as an asymptomatic or painful slow-growing mass, ranging in size from 1.5 to 10 cm (mean, 3.7 cm). The preoperative duration was usually more than 1 year. SCPFT may occur anywhere on the body, but most lesions appear on the lower limbs, particularly the thighs. Histopathologically speaking, the tumors were confined to the deep dermis and superficial subcutis. They were composed of fascicles or sheets of epithelioid to spindle cells with abundant granular or glassy eosinophilic cytoplasm and bizarre, hyperchromatic nuclei. Marked pleomorphism but low mitotic activity was noted in all cases. Immunohistochemically speaking, all tumors showed strong CD34 positivity, and approximately half expressed cytokeratins. Endothelial, myogenic, and melanocytic markers were negative. Ultrastructural examination of samples from 2 cases3,8 confirmed fibroblastic differentiation. Positron emission tomography in one case8 showed the abnormal uptake of 2-(18F) fluoro-2-deoxy-d-glucose, with a maximum standardized uptake value of 2.57, which was consistent with its intermediate malignancy. Cytogenetic studies of one case8 disclosed chromosomal translocation of t(2;5)(q31; q31), which was hypothesized to be a specific chromosomal aberration. All patients were treated with surgery. During the mean follow-up period of 6.5 months, no recurrences or metastases occurred, with the exception of one patient1 who developed regional lymph node metastasis 7 years after incomplete excision of the primary lesion.TABLE 1.: Clinical Features and Disease Outcomes of 38 Previously Reported Cases of Superficial CD34-Positive Fibroblastic Tumor and Our PatientTABLE 1-A.: Clinical Features and Disease Outcomes of 38 Previously Reported Cases of Superficial CD34-Positive Fibroblastic Tumor and Our PatientSCPFT must be distinguished from other mesenchymal neoplasms with pleomorphism and low mitotic activity or CD34 positivity. Myxoinflammatory fibroblastic sarcoma differs from SCPFT because it is characterized by a multilobulated architecture with prominent paucicellular myxoid zones and usually shows TGFBR3-MGEA5 translocation.11 Pleomorphic hyalinizing angiectatic tumor has distinctive features such as thick-walled ectatic vessels with prominent perivascular hyalinization. Myxofibrosarcoma exhibits a myxoid multinodular growth pattern, curvilinear thin-walled blood vessels, perivascular tumor cell condensation, and much higher mitotic rates. Both atypical fibroxanthoma and undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma have brisk mitotic activity and CD34 negativity. Atypical fibrous histiocytoma is usually observed against a background of conventional fibrous histiocytoma and lacks CD34 expression. Both dermatofibrosarcoma protuberans and fibrosarcoma exhibit monomorphic cytology. Malignant granular cell tumor is a relatively monomorphic spindle cell sarcoma with S-100 protein positivity. In conclusion, SPCFT is characterized by marked pleomorphism, an extremely low mitotic rate, and strong CD34 positivity. It behaves as an intermediate malignancy with rare recurrence and metastasis. Recognition of this novel disease entity may help dermatologists to discriminate SPCFT from other potential morphological mimics.

Knowledge of biochemical and molecular events during burn wound healing may optimize treatment of patients with thermal injuries. Substance P (SP), a neuropeptide present in C fibers of the skin, has been implicated as a mediator of inflammation and wound healing. This neuropeptide induces vasodilitation and vascular permeability by stimulating endothelial cells to round up, vascular smooth cells to relax, and mast cells to release histamine. SP also induces cytokine release by macrophages and neutrophils. Because many of the functions of SP seemed relevant to wound repair in burns, we used immunocytochemistry to characterize SP+ nerve fibers in healing human burn wounds. Deep partial-thickness burns collected from 20 patients at the time of excision and grafting were formalin fixed, paraffin-embedded, sectioned, and labeled with a monoclonal antibody to SP with use of an immunoperoxidase technique. Our tissue samples included normal skin and 20 specimens from postburn days 2 through 49. In normal adult skin, SP+ nerve fibers surrounded vessels throughout the skin and extended from the papillary dermis into the epidermis. SP+ fibers were absent in early wound beds. SP immunostaining did occur in the advancing epidermis, endothelial cells, and mast cells. SP+ fibers could be identified in the deep dermis and subjacent to the advancing epithelium before the wound beds. Maximum numbers of SP+ fibers were present subjacent to the advancing epithelium at 2 weeks after burn injury. After 4 weeks, the distribution of SP+ fibers in reepithelialized areas was similar to that of normal skin. Our data corroborate published reports of SP+ fiber regeneration in guinea pig burns and correlates with clinical observations of pain and pruritus in patients with thermal injuries. The absence of SP+ fibers in the early wounds with SP immunostaining in the epidermis and extracellular matrix suggests that SP may be released from injured nerves and supports neurogenic mediation of inflammation and vasodilitation in early wound repair. Repopulation of the wound beds with SP+ fibers appeared to follow neovascularization originating in the deep reticular dermis and wound edge.

Stiff skin syndrome is a sclerodermalike disorder that presents in infancy or early childhood with rock-hard skin, limited joint mobility, and mild hypertrichosis in the absence of visceral or muscle involvement, immunologic abnormalities, or vascular hyperreactivity. We describe 6 children who fit criteria for stiff skin syndrome. A review of the clinical range of this disorder and discussion of the differential diagnosis is presented. The age at onset in our cases ranged from infancy to 6 years of age. Stony-hard skin was noted mostly on the thighs, buttocks, and lower back with shoulder and arm involvement in 2 cases. There was associated hypertrichosis in 3 of 6 cases. Extracutaneous manifestations consisted primarily of joint restriction, and several patients had resulting postural and thoracic wall irregularities. Histopathologically, our cases showed areas of fascial sclerosis or showed increased fibroblast cellularity with thickened, sclerotic, horizontally oriented collagen bundles in the deep reticular dermis and/or subcutaneous septa without associated inflammation. Stiff skin syndrome is characterized by an early, insidious onset of stony-hard skin, often with associated contracturelike joint restriction, hypertrichosis, and postural and thoracic wall abnormalities. Supportive histopathologic findings consisting of either fascial sclerosis or increased fibroblast cellularity with sclerotic collagen bundles in the deep reticular dermis and/or subcutaneous septa may help to confirm this diagnosis.