Intraepithelial sebaceous carcinoma of the eyelid misdiagnosed as Bowen's disease

BACKGROUND: Sebaceous carcinoma (SC) is well known for its ability to masquerade clinically and histologically as a variety of periocular conditions resulting in a delayed diagnosis. We present a series of periocular SC cases and discuss the difficulties in histopathological diagnosis when this tumor presents with a Bowenoid pattern of intraepithelial spread. METHODS: A retrospective case study of all patients with SC of the eyelid treated in our Hospital, from 1997 to 2004, was conducted. RESULTS: Eight patients were identified (four females and four males). Seven cases involved the upper eyelid. Initial clinical diagnoses included blepharitis (three cases), blepharoconjunctivitis (one case), cicatrizing conjunctivitis (one case), and lid lesions (two cases). Histopathologically, 87.5% of cases were misdiagnosed as Bowen's disease (BD) on the initial biopsy. Six of these cases showed no invasive disease on the initial biopsy and were eventually found to be invasive SC on subsequent excisions. In one case, the tumor was wholly in situ. Delay in diagnosis ranged from 0 to 56 months. CONCLUSIONS: SC should always be considered in the histological differential diagnosis of any eyelid lesion which resembles BD, particularly if the upper eyelid is involved or if multivacuolated cytoplasmic clear cell changes are seen.     

Intraepidermal sebaceous carcinoma with superficial dermal invasion of the nipple

Sebaceous carcinoma (SC) is a rare malignant neoplasm usually presenting as an ocular lesion or, less commonly, an extraocular cutaneous lesion mostly on the head and neck, whereas it seldom found on other sites. We present a case of a 56-year-old woman with SC on her left nipple. To our knowledge, this is the second reported SC arising in the nipple, but may be the first case of SC of the nipple displaying predominance in intraepidermal proliferation with superficial dermal invasion—a very seldom described growth pattern of extraocular SC in literature. An early invasive stage of the rare intraepidermal variant is suggested, with the location of the originating tumor cells being different from that of the usual intradermal cases. Free/ectopic sebaceous gland is one of the possible origins.     

Pigmented epidermotropic breast cancer metastases: A rare variant with a particularly unusual feature

Pigmented epidermotropic breast cancer metastases are a rarity, often clinically misdiagnosed as melanocytic lesions. Histopathologically, they show a dermal proliferation of neoplastic metastatic cells that extend to the overlying epidermis in a pattern identical to that seen in primary Paget disease (PD). Differential diagnosis should be established with entities with a similar presentation, such as pigmented mammary PD and malignant melanoma. Immunohistochemistry may be useful for this purpose. We present a new case of pigmented epidermotropic breast cancer metastases with a particularly unusual feature: the absence of dermal infiltration by neoplastic cells, thus considered as pure epidermotropic metastatic involvement.     

The impact of carbonylated proteins on the skin and potential agents to block their effects

Carbonylated proteins (CPs) are synthesized by reactions between amino groups in proteins and reactive aldehyde compounds (RAC) yielded from lipid peroxidation initiated by reactive oxygen species (ROS). In the skin, CPs are detected in a higher frequency at sun‐exposed sites of the skin in elderly subjects. Since CPs in the stratum corneum (SC) have been reported to correlate with skin water content and transepidermal water loss, it is considered that the accumulation of CPs in the SC involves the loss of skin moisture functions. However, the roles of CPs in the dermis on skin physiology are still unclear. The purpose of this study was to investigate the roles of CPs in the dermis during the progression of photoaged skin and to propose a method to prevent or reduce the synthesis of CPs. The exposure of human normal dermal fibroblasts to CPs increased intracellular ROS levels and the synthesis of intracellular CPs. In addition, CPs caused morphological changes of fibroblasts. Furthermore, CPs caused alterations of mRNA expression levels of dermal matrix‐related proteins, such as upregulating MMP‐1 and IL‐8. These results indicated that CPs disrupt construction of the dermal matrix. On the other hand, α‐tocopherol and β‐carotene suppressed the synthesis of RAC during lipid peroxidation which resulted in the reduction of UVA‐induced CPs in the SC. From these results, we propose that extracellular CPs increase intracellular ROS levels and contribute to alterations of the dermal matrix. To prevent the synthesis of CPs, the application of α‐tocopherol or β‐carotene could be effective.     

Metastasizing epithelioid hemangioendothelioma of the nose in childhood

Epithelioid hemangioendothelioma (EHE) arising in the skin is extremely rare, and the majority of documented cases have developed in soft tissues or parenchymatous organs. We report on a 9-year-old boy who presented with a painful erythematous plaque on the nose. Histopathological findings showed a dermal tumor composed of epithelioid cells with moderate cellular atypia and characteristic intracytoplasmic vacuoles. Immunohistochemical stainings confirmed the vascular nature of the tumor. On the basis of these findings, the diagnosis of an EHE was made. Then, two cervical lymph nodes were excised and adjuvant therapy with interferon alpha 2b was initiated. Eighteen months after diagnosis, there is no evidence of local tumor recurrence or metastases. To our knowledge, this is the first report of a metastasizing cutaneous EHE on the nose in childhood. As our case shows, this rare tumor entity has to be considered as a differential diagnosis in neoplasms of the skin, even in childhood.     

儿童获得性大疱性表皮松解症一例

报道1例儿童获得性大疱性表皮松解症.患者女,12岁,因全身反复水疱、大疱和糜烂面3个月入院.患者弱智,父母非近亲结婚,无家族史.入院时表现全身大片糜烂面,包括手足、膝关节周围和股臀部,同时躯干、四肢正常或水肿性红斑基础上紧张性水疱、大疱.治疗过程中突然发生躯干、四肢大量紧张性水疱.组织病理提示,表皮下水疱,免疫荧光结果见表皮基底膜带IgG和C3线状沉积,盐裂后沉积限于真皮侧.ELISA检测BP180和BP230阴性.采用大剂量糖皮质激素联合四环素口服取得满意疗效.

Abstract：

A case of epidermolysis bullosa acquisita (EBA) in childhood is reported. A 12-year-old girl was hospitalized for a 3-month history of recurrent blisters, bullae and erosions on the trunk and limbs. The girl had mental retardation but no family history of similar disorders. The marriage between her parents was not consanguineous. Physical examination on admission revealed large erosions with moderate oozing on the hands and feet, around the knees and on the buttock and thighs. There were scattered tense blisters and bullae arising in normal skin or edematous erythema on the trunk and limbs. During the treatment course the patient suddenly developed a number of tense blisters over the whole integument on the trunk and limbs. Skin biopsy showed subepidermal bullae with moderate perivascular infiltration of neutrophils and eosinophils. Direct immunofluorescence (DIF) revealed linear IgG and C3 deposition along the basal membrane zone, which was on the dermal side of salt-split skin on indirect immunofluorescence (IIF). ELISA detected no serum antiBP180 or -BP230 antibodies in the patient. A diagnosis of EBA was made. The patient was successfully controlled by intravenous steroids combined with oral tetracycline.     

Skin hydration: a review on its molecular mechanisms

Water is absolutely essential for the normal functioning of the skin and especially its outer layer, the stratum corneum (SC). Loss of water from the skin must be carefully regulated, a function dependent on the complex nature of the SC. The retention of water in the SC is dependent on two major components: (1) the presence of natural hygroscopic agents within the corneocytes (collectively referred to as natural moisturizing factor) and (2) the SC intercellular lipids orderly arranged to form a barrier to transepidermal water loss (TEWL). The water content of the SC is necessary for proper SC maturation and skin desquamation. Increased TEWL impairs enzymatic functions required for normal desquamation resulting in the visible appearance of dry, flaky skin. There have been recent discoveries regarding the complex mechanisms of skin hydration. In particular, it has been discovered that glycerol, a well-known cosmetic ingredient, exists in the SC as a natural endogenous humectant. Hyaluronan, which has been regarded mainly as dermal component, is found in the epidermis and is important for maintaining normal SC structure and epidermal barrier function. More importantly, the discovery of the existence of the water-transporting protein aquaporin-3 in the viable epidermis and the presence of tight junction structures at the junction between the stratum granulosum and SC have brought new insights into the mechanisms of skin water distribution and barrier function.     

Congenital segmental dermal melanocytosis in an adult.

BACKGROUND--Dermal melanocytosis is characterized by the presence of melanocytes in the dermis. There are several morphologic forms, such as the blue nevus, the mongolian spot, the nevus of Ota, and the nevus of Ito. In this article, we report an unusual case of dermal melanocytosis. OBSERVATIONS--A 28-year-old white woman was referred to us, as she had an extensive, speckled gray-blue pigmentation on the right aspect of her trunk that was in a segmental pattern. The lesion had been present at birth. Histologic and ultrastructural examinations revealed sparse, elongated dermal melanocytes. CONCLUSIONS--We comment on the differential diagnosis with classic recognized forms of dermal melanocytosis. We also review other isolated cases of unusual dermal melanocytosis. This is a distinct case, clinically different from previously reported cases in the literature; we propose the term "congenital segmental dermal melanocytosis" to name this case.     

Intradermal spindle cell/pleomorphic lipoma of the vulva: case report and review of the literature

BACKGROUND: Spindle cell/pleomorphic lipoma (SC/PL) is a benign adipose tissue tumor that usually affects the subcutaneous tissues of shoulders, backs, and neck region of middle-aged male patients. Histologically, it is characterized by the presence of primitive CD34-positive spindle cells arranged in short fascicles, bizarre floret-like multinucleated giant cells, mature adipocytes, and a small number of lipoblasts. Recently, an intradermal subset has been described, which mainly affects female patients and presents a wider antomical distribution when compared to the classical variant of SC/PL. METHODS: We report a case of intradermal SC/PL affecting the labium majus of a 56-year-old female patient. RESULTS: The histological examination disclosed the typical histological features, however the lesion showed poorly demarcated and infiltrative borders, as well as involvement of dermal nerves. The immunohistochemical analysis according to streptovidin-biotin-peroxidase technique showed immunoreactivity for CD34 and vimentin in the spindle cells, as well as S100 protein and vimentin in the adipocytic cells. CONCLUSIONS: To the best of our knowledge, this is the first case of intradermal SC/PL affecting the vulvar region. Care must be taken not to misdiagnosis this rare tumor as well-differentiated liposarcoma, cellular angiofibroma, solitary fibrous tumor, and cutaneous neurofibroma.     

Benign Nerve Sheath Myxoma in an Infant Misdiagnosed as Infantile Digital Fibromatosis

Herein we present the case of a 16‐month boy, clinically diagnosed with infantile digital fibromatosis, but 9 months after continued growth, the mass was excised and the histopathologic diagnosis was that of a benign nerve sheath myxoma. We present this case to emphasize that nerve sheath myxomas (also known as myxoid neurothekeoma) should be included in the differential diagnosis of dermal nodules in infants.     

MIB-1 monoclonal antibody to determine proliferative activity of Ki-67 antigen as an adjunct to the histopathologic differential diagnosis of Spitz nevi

BACKGROUND: The histopathologic differential diagnosis of Spitz nevus (SN) from malignant melanoma (MM) may be difficult. OBJECTIVE: Our purpose was to determine the staining pattern and usefulness of MIB-1 antibody, which recognizes Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, as an adjunct to the histopathologic differential diagnosis of SN. METHODS: Twenty-five compound SNs, 27 MMs, and 26 compound nondysplastic melanocytic nevi (MNs) were immunostained with the MIB-1 antibody. RESULTS: The mean counts of MIB-1--stained tumor cells of the epidermal and dermal components, both alone and together, were significantly lower in SNs and MNs than in MMs (P <.0001). The dermal counts showed the best discriminating power. In addition, the mean dermal/epidermal count ratios for MIB-1 in SNs and MNs (0.25 and 0.23, respectively) were significantly lower than the corresponding ratio (0.94) in MMs (P <.0001). CONCLUSION: MIB-1-stained tumor cell counts, especially of the dermal component, and dermal/epidermal MIB-1 count ratios may be helpful as an adjunct to the histopathologic differential diagnosis of SN.     

Measurement of hydration in the stratum corneum with the MoistureMeter and comparison with the Corneometer

Background/purpose: MoistureMeter is a novel capacitive device for measuring the hydration of stratum corneum (SC). The capacitor ‘plates’ are formed by the probe material and the well‐conducting epidermal–dermal skin layers, while the dry layer of SC acts as an ‘insulator’ of the capacitor. Due to this measurement principle, the measurement depth is not constant, but equal to the thickness of the dry layer of SC. The present study was undertaken to test the MoistureMeter SC‐2 in an experimental setup simulating the uppermost skin structure. The sensitivity of the MoistureMeter was compared with a conventional device Corneometer CM 820 in eight healthy volunteers. Methods: The experimental setup consisted of a polyethene foil simulating SC and a mixture of cellulose and saline simulating the underlying skin layers with a high water content. The hydration of SC of volar forearm was measured in eight healthy volunteers both with the MoistureMeter SC‐2 and Corneometer CM 820 after the application of three different skin formulations: base, base plus salt (2 wt% NaCl), base plus salt and glycerin (5 wt%). In the sorption–desorption test, the skin was wetted with a drop of water and the dehydration was followed with both devices for 2 min. Results: The test with the experimental setup agreed with the results predicted by the mathematical capacitance model. The hydration values of the MoistureMeter SC‐2 and Corneometer CM 820 correlated well (R=0.75), but the relative range of readings with the MoistureMeter was approximately three times larger than with Corneometer. The MoistureMeter was insensitive for the salt (2 wt% NaCl) of the formulation and differentiated the hydration effect of glycerin better than the Corneometer. In the sorption–desorption test, the MoistureMeter demonstrated the individual differences between the volunteers, whereas with the Corneometer the differences were minimal. Conclusion: The capacitive measuring principle of the MoistureMeter was demonstrated in an experimental arrangement. Although both instruments yielded equivalent data with the base formulation, the MoistureMeter was a more sensitive device than the Corneometer CM 820 and independent of added salt in the formulations.     

Prominent papillary dermal edema in dermatophytosis (tinea corporis)*

Background: Commonly described histologic ‘clues’ to the diagnosis of dermatophytosis include neutrophils in the stratum corneum and/or epidermis, compact orthokeratosis and identification of fungal hyphae between two zones of cornified cells. Prominent (striking) papillary dermal edema (PPDE) is not commonly reported with dermatophytosis (tinea corporis). Methods: We observed an index case in which PPDE was the salient histologic finding in lesions of tinea corporis. Fifteen additional cases of tinea corporis with PPDE were diagnosed in our dermatopathology laboratory over a 9‐year period. The clinical and histologic findings were reviewed. Results: All 16 cases occurred on the extremities of women, 11 of whom had skin of color. The submitted clinical differential diagnoses varied widely, but included some of the diseases ‘classically’ associated with PPDE, as well as other blistering eruptions. In several cases, only a few dermatophyte hyphae were identified in tissue sections. Conclusions: Our case series serves as a reminder that dermatophytosis should be strongly considered in the differential diagnosis of lesions with PPDE. Fungal culture may be helpful in patients whose biopsies show PPDE, negative periodic acid‐Schiff (PAS) stains and who fail to respond to conventional anti‐inflammatory therapy. This study lends support for the routine use of PAS stains in biopsies of inflammatory dermatoses. Hoss D, Berke A, Kerr P, Grant‐Kels J, Murphy M. Prominent papillary dermal edema in dermatophytosis (tinea corporis).     

Sebaceous carcinoma and the T-antigen

Carcinomas of sebaceous glands are uncommon. They are traditionally classified into ocular and extraocular sebaceous carcinomas (SC). Ocular SC tend to be more common and more aggressive than extraocular SC. However, the latter can occasionally follow a fatal course. Histologically, SC should be classified into 1) SC in situ; 2) SC, infiltrating, low-grade with or without pagetoid spread; 3) SC, infiltrating, high-grade, with or without pagetoid spread; and 4) SC with extraocular and extracutaneous involvement, including metastases. Immunohistochemistry plays a minor role in the diagnosis of SC. Thomsen-Friedenreich (T) antigen can be a helpful tool in differentiating SC (strong T-antigen reactivity in basaloid cells) from other mimicking neoplasms (basaloid cells are T-antigen negative). The histologic differential diagnosis, pathogenesis, and management of SC are reviewed.     

Reticular erythema with focal mid‐dermal elastophagocytosis (REMDE)

A 57‐year‐old man presented with a persistent arcuate partly reticular erythema of the upper chest. Histopathological examination revealed an upper and mid‐dermal perivascular and interstitial dermatitis with macrophages which had engulfed elastic fibers. Additionally a focal dermal elastolysis was observed. The characteristic clinicopathological constellation has hitherto been reported in only 3 cases, including our case. Presumably, the disease belongs to a spectrum of clinical manifestation of mid‐dermal elastolysis. It is suggested to gather future cases under the provisional diagnosis ‘‘reticular erythema with focal mid‐dermal elastophagocytosis” (REMDE) to gain more insights into this rare disease.     

Congenital self-healing reticulohistiocytosis mimicking diffuse neonatal hemangiomatosis

Congenital self-healing reticulohistiocytosis (CSRH), a rare benign variant of Langerhans cell histiocytosis (LCH), is characterized by (a). congenital skin lesions, (b). a healthy infant with no systemic involvement, (c). the histopathologic finding of a Langerhans cell infiltrate and (d). spontaneous involution within the first year of life without sequelae. We report a Taiwanese girl born with widespread hemangioma-like lesions. The diagnosis of LCH was confirmed by finding a diffuse dermal infiltrate of S-100-protein- and OKT6 (CD1a)-positive mononuclear cells and the presence of Birbeck granules in 10% of the mononuclear cells ultrastructurally. The diagnosis of CSRH was further established by rapid and complete involution of the lesions in 3 months. No recurrence was noted for 7 years. Our case illustrates that CSRH can mimic diffuse neonatal hemangiomatosis clinically; thus, it is important to include CSRH in the differential diagnosis of congenital or neonatal hemangiomatosis.     

Histology simulating reticulosis in persistent nodular scabies

Six patients with persistent nodular scabies are described. Initially the diagnosis was in doubt, and thus a lesion was biopsied in each case. The histology bore a striking resemblance to that of malignant lymphoid neoplasm in five cases. In the absence of a clinical diagnosis it was reported as such by experienced skin histopathologists. In the remaining case an accrues was seen histologically, but the type and extent of the dermal infiltrate suggested a concomitant adverse drug reaction. We feel that these histological appearances may be misleading and that even with accurate clinical details the true diagnosis may be made only on the subsequent progress of the patient.     

Expression of α‐methylacyl‐CoA racemase (P504S) in sebaceous neoplasms

Background: α‐Methylacyl‐CoA racemase (AMACR), also known as P504S, is a protein that plays an important role in mitochondrial and peroxisomal β‐oxidation of branched‐chain fatty acid and bile acid intermediates. AMACR has been established as a valuable diagnostic marker for prostate cancer and has recently been shown to be useful in the diagnosis of colorectal carcinoma. Despite the importance of lipid metabolism in sebum production by sebaceous glands of the skin, there are no studies evaluating the expression of AMACR in sebaceous neoplasms. Methods: Five samples of normal sebaceous glands as well as five cases each of sebaceous hyperplasia (SH), sebaceous adenoma (SA), basal cell carcinoma (BCC) with sebaceous differentiation and extraocular sebaceous carcinoma (SC) were evaluated for immunohistochemical (IHC) expression of AMACR. Each case was reviewed by a single dermatopathologist and graded using a semi‐objective grading schema. Results: Normal sebaceous glands showed strong (4+) expression of AMACR. Among sebaceous neoplasms, SH showed the highest expression (4+), SA and BCC with sebaceous differentiation showed varied expression (2+ and 1+, respectively), and extraocular SC showed no expression of AMACR. Conclusions: The expression of AMACR is increased in benign sebaceous glands and SH; with decreasing AMACR expression in tumors with less sebaceous differentiation (i.e. SA and SC). These findings provide insight into the potential pathogenesis of sebaceous neoplasms while assisting in the microscopic distinction of SA from SC. Halsey MA, Calder KB, Mathew R, Schlauder S, Morgan MB. Expression of α‐methylacyl‐CoA racemase (P504S) in sebaceous neoplasms.     

Atypical cutaneous myeloid infiltrate in myelodysplastic syndrome: a case report

We report the case of a 31-year-old man with an atypical myeloid dermal infiltrate manifested by a 1.5-year history of recurrent erythematous plaques over his body that previously were shown to be culture positive for Staphylococcus aureus and had responded well to oral antibiotic treatment. The ultimate diagnosis was refractory anemia with excess blasts-2 (RAEB-2), a myelodysplastic syndrome (MDS). Whether it is a specific or nonspecific lesion, cutaneous involvement in MDS is a poor prognostic factor. Leukemia cutis (LC), a specific dermal infiltrate of malignant hematopoietic cells, particularly is associated with progression to acute leukemia. However, the pathology of our patient's lesions revealed a more sparse sprinkling of atypical mononuclear cells indicative of an inflammatory recruitment of leukemic cells to the dermis. Nonetheless, the guarded prognosis of this high-risk subtype of MDS mandates continued monitoring for development of LC and progression to leukemia.