Poorly differentiated cutaneous apocrine carcinomas: histopathological clues and immunohistochemical analysis for the diagnosis of this unusual neoplasm.

Primary cutaneous apocrine carcinoma (PCAC) is a rare cutaneous malignancy that is derived from apocrine glands. Histologically, these tumours can appear well-differentiated where diagnosis should be relatively straightforward. However, occasionally these tumours can exhibit high-grade features, and in such instances the diagnosis can be challenging. A retrospective analysis of 12 cases of poorly differentiated PCAC, obtained from large academic institutions, was performed, and summarised below. Immunohistochemical studies were performed in all cases with antibodies against CK7, p63, CAM 5.2, GCDFP-15, GATA3, CEA, PR, ER, HER2, calponin, SMA, androgen receptor and EMA. All 12 cases were poorly differentiated; however, there were some histopathological clues to the diagnosis of apocrine carcinoma; namely, the presence of focal glandular formation, acrosyringial involvement and the presence of single 'pagetoid' cells within epidermis. All tumours were consistently positive for CK7, GATA3 and GCDFP-15 and negative for p63. The tumours had variable expression of CAM5.2, CEA, ER, PR, HER2, androgen receptor and EMA. In three cases, there was a preservation of the myoepithelial cell layer (with calponin and SMA), which also confirmed the primary cutaneous origin. PCAC is a difficult neoplasm to diagnose, as it can appear identical to metastatic carcinomas. We describe 12 cases of poorly differentiated PCAC, highlighting their salient clinical, histopathological and immunohistochemical features, and discuss the potential diagnostic pitfalls in distinguishing this entity from other malignant neoplasms. Our results indicate that a combination of thorough histological inspection coupled with an adequate battery of immunohistochemical stains is necessary to support the diagnosis of PCAC.

An update on viral-induced cutaneous lymphoproliferative disorders. CME Part I.

Viral-induced cutaneous T-cell lymphomas are an uncommon group of lymphoproliferative disorders characterized by a viral infection of T and natural killer (NK) cells. This group of cutaneous T-cell lymphomas is more commonly encountered in Asians and Native Americans from Central and South America compared with Western populations. Viral-associated lymphoproliferative disorders include a spectrum of entities that range from nonneoplastic lesions, such as chronic active Epstein-Barr virus infection and infective dermatitis to malignant diseases, such as extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and adult T-cell leukemia/lymphoma. This review article will focus on hydroa vacciniforme-like lymphoproliferative disorder, extranodal NK/T-cell lymphoma, adult T-cell leukemia/lymphoma, lymphomatoid granulomatosis, and Epstein-Barr virus-positive mucocutaneous ulcers. We will review the pathogenesis of these conditions and the challenges of making a timely diagnosis in early-stage disease and discuss the common clinicopathologic manifestations, mutational landscape, and approaches to treat these highly aggressive and frequently lethal types of lymphoma.

Low-Grade Hidradenocarcinoma of the Foot With Metastasis to a Lymph Node.

ABSTRACT: Hidradenocarcinoma (HAC) is a rare adnexal tumor associated with the potential for locoregional recurrence and systemic metastasis. The clinical appearance of HAC is nonspecific, frequently presenting as a solitary firm subcutaneous nodule or plaque on the head and neck region or distal extremities. These tumors show histomorphologic heterogeneity, as they can be low and high grade. Distinguishing HAC from hidradenoma, especially the low-grade variant of HAC, can be challenging as both tumors can show histologic overlapping features. In this article, we describe a case of a 33-year-old patient presenting with a low-grade HAC of the plantar foot who was subsequently found to have lymph node metastasis.

The Utility of Myoepithelial Cell Layer Identification in Adnexal Carcinomas.

ABSTRACT: The distinction of metastatic carcinomas to the skin (MCS) from cutaneous adnexal carcinomas can pose a significant diagnostic challenge. The differentiation between (MCS) from a primary cutaneous adnexal tumor is one of the most difficult tasks in the field of dermatopathology, and immunohistochemistry has only been partially helpful in solving this problem. In routine diagnostic surgical pathology, it is essential to identify the myoepithelial cell layer by immunohistochemistry to distinguish between an in situ and invasive breast carcinomas and when establishing the presence of microinvasion. The purpose of this study was to evaluate the role of myoepithelial cell layer expression in difficult cases of cutaneous adnexal carcinomas in which histologically it was challenging to separate them from MCS. We studied 38 adnexal carcinomas and evaluated them for myoepithelial markers to confirm the primary nature of the neoplasm. The used markers to search for myoepithelial cell layer retention included calponin, p63, and smooth muscle actin. Of the 38 cases, we found that 13 cases showed myoepithelial layer retention, confirming the primary cutaneous origin of the neoplastic process. The results of our study suggest that the presence of an identifiable retention of the myoepithelial cell layer in adnexal carcinomas could be a useful adjunct observation in the diagnosis of primary adnexal carcinomas, especially in the clinical setting of a questionable primary adnexal versus metastatic neoplasm.

Actionable Mutation Profile of Sun-Protected Melanomas in South America.

ABSTRACT: Melanomas that arise in sun-protected sites, including acral and oral mucosal melanomas, are likely under the control of unique, specific mechanisms that lead to mutagenesis through various pathways. In this study, we examined somatic mutations in tumors by targeted sequencing using a custom Ion Ampliseq Panel, comprising hotspots of 14 genes that are frequently mutated in solid tumors. Tumor DNA was extracted from 9 formalin fixation, paraffin-embedded sun-protected melanomas (4 primary oral mucosal melanomas and 5 acral lentiginous melanomas), and we identified mutations in the NRAS , PIK3CA , EGFR , HRAS , ERBB2 , and ROS1 genes. This study reveals new actionable mutations that are potential targets in the treatment of photo-protected melanomas. Additional studies on more of these melanoma subtypes could confirm our findings and identify new mutations.

In Vivo Reflectance Confocal Microscopy of Adnexal Tumors: Evaluation of Trichoepithelioma, Sebaceoma, and Fibrofolliculoma.

ABSTRACT: Cutaneous adnexal tumors are benign and malignant neoplasms that undergo morphological differentiation into cutaneous adnexa, comprising pilosebaceous, eccrine, or apocrine units. Reflectance confocal microscopy is a noninvasive diagnostic method that enables in vivo visualization of tissues at a similar resolution as conventional histopathology. The use of this method in skin imaging over the past several years has improved dermatological diagnoses, potentiating its wide application, especially for benign and malignant skin tumors. We describe the use of reflectance confocal microscopy in cases of trichoepithelioma, sebaceoma, and fibrofolliculoma and correlate the resulting clinical, histopathological, and confocal microscopy images.

Poorly Differentiated Scrotal Carcinoma With Apocrine Immunophenotype.

ABSTRACT: Cutaneous carcinoma of the scrotum is rare with the most common type being squamous cell carcinoma. Here, we report 6 cases of poorly differentiated carcinoma with apocrine immunophenotype. Mean age at presentation was 68 years (range: 31-91 years). Clinical presentation included eczematous rash over mass, scrotal cyst, ulcerated mass, and mass. Tumor size ranged from 1.2 to 5.5 cm (average 2.5 cm). The tumors were solid with involvement of the dermis/hypodermis and composed of cords and nests of eosinophilic cells displaying nuclei with prominent nucleoli and surrounded by desmoplastic stroma. Focal squamous differentiation was evident in one case (17%). An intraductal component was seen in one case (17%). Pagetoid spread in the epidermis was seen in 3 cases. There was no morphologic evidence of apocrine differentiation. By immunohistochemistry, the tumor cells were positive for GCDFP-15 (n = 6/6), GATA3 (n = 6/6), CK7 (n = 5/5), AR (n = 4/4), and mammaglobin (n = 3/5). Five (83%) patients had metastases at diagnosis. Treatment included wide local excisions and inguinal lymph node dissection, followed by chemotherapy (gemcitabine, carboplatin; n = 3), trastuzumab/Lupron (n = 1), tamoxifen/Arimidex (n = 1), and radiotherapy (n = 1). Two patients (40%) were dead of disease, less than 2 years from diagnosis. Four patients developed metastases to lymph nodes, liver, bones, and lungs. Molecular analysis (n = 2) detected a HER-2 mutation in one and microsatellite instability in another. Although the presence of an intraepidermal pagetoid component could hint toward the diagnosis of invasive extramammary Paget disease, tumors without an intraepidermal component could be diagnostically challenging given the lack of morphologic evidence of apocrine differentiation.

Histomorphological and immunophenotypical spectrum of cutaneous myoepitheliomas: A series of 35 cases.

Myoepithelial tumors comprise a group of mesenchymal lesions that show heterogeneous histomorphological features, including dual epithelial, neural, and myoid differentiation. Cutaneous myoepithelioma is a rare neoplasm that is composed primarily of myoepithelial cells and represents one end of a histopathological spectrum of cutaneous myoepithelial neoplasms including chondroid syringoma and myoepithelial carcinoma. These tumors display a wide histopathological spectrum and immunophenotypical profile often showing epithelial and myoepithelial differentiation. In this series, we studied 35 cases of cutaneous myoepitheliomas. Our cases highlighted the broad histopathological range where most cases showed a non-infiltrative and non-encapsulated tumor exclusively located in the dermis and with no subcutaneous involvement. The majority of our cases had a solid growth pattern (syncytial pattern) and the remainder of cases had a multinodular growth pattern. The tumor cells were epithelioid in 23 cases, spindled in eight cases and there was a mixture of epithelioid and spindled cells in four cases. Mitotic figures ranged from 0 to 5 per 10 HPF. By immunohistochemistry epithelial membrane antigen (EMA) was expressed in 59% of cases S100 was positive in 88% of cases, CAM 5.2 was positive in 16% of cases, AE1/AE3 was positive in 44% of cases, p63 was positive in 17% of cases, smooth muscle actin was positive in 38% of cases, desmin was positive in 6% of cases, calponin was positive in 22% of cases, and glial fibrillary acidic protein was positive in 36% of cases. In addition, there were five cases without EMA, keratin, or p63 expression that only showed S100 expression. We describe a large series of cutaneous myoepitheliomas delineating their histomorphological spectrum and immunophenotypical profile. Awareness of some of the unusual histopathological features and the heterogeneous immunohistochemical may pose difficulties for the diagnosis.

Primary Cutaneous Aspergillosis in Immunocompetent Patients Due to Aspergillus niger: A Report of 4 Cases.

ABSTRACT: Primary cutaneous aspergillosis is a cutaneous fungal infection due to the direct inoculation of spores of Aspergillus species into the disrupted skin. Primary cutaneous aspergillosis presents with a variety of localized cutaneous lesions, such as erythematous macules, papules, plaques, or nodules that can progress to necrosis, erosion, ulceration, or fistulization. Many species of Aspergillus can cause the disease, and one of them is Aspergillus niger that rarely affects immunocompetent patients and that has peculiar characteristics on the histopathological examination. We present a series of 4 cases of immunologically competent patients presenting with primary cutaneous aspergillosis caused by A. niger.

Sebaceous Carcinomas: A Clinicopathological Comparison of Ocular and Extraocular Variants.

ABSTRACT: Sebaceous carcinomas (SC) are rare tumors and are currently classified into ocular and extraocular variants. Both variants of SC have very different clinical behavior and different histomorphologic appearance; however, published data are confounding as literature describes prognosis of both variants is similar or even that extraocular variants are more aggressive. In this study we evaluated the clinical and the histopathology of ocular and extraocular SC to confirm the difference between them. We performed a retrospective review of SC in which we studied the clinical and histomorphologic features of 106 cases, including 39 cases of ocular SC and 67 cases of extraocular SC. Only 2/67 cases of extraocular SC had multiple recurrences and none of them metastasized as opposed to our cases of ocular SC wherein 21/39 cases were locally aggressive with multiple recurrences and 5 cases metastasized. Histologically, both neoplasms showed major distinct morphologic features including poor differentiation in cases of ocular SC and well-differentiated tumors in the extraocular anatomic sites. To the best of our knowledge, this is the first case series of SC that compares the clinicopathologic features of ocular and extraocular variants. Awareness of such discrepancy is key to understand this disease and to possibly diagnose and manage these patients accordingly.

Reproducible Histopathologic Features in Cases of Basal Cell Carcinoma With Neuroendocrine Expression: A Clinicopathologic Study of 24 Cases With a Potential Diagnostic Pitfall.

ABSTRACT: Basal cell carcinomas (BCCs) are common malignancies that usually show clear histomorphologic features, but in certain instances, it can display different patterns of differentiation leading to potential diagnostic confusion. BCCs with neuroendocrine differentiation/expression have been mentioned only briefly in the literature. In this study, we present cases of BCCs with neuroendocrine differentiation/expression that demonstrate reproducible histopathological features. Twenty-four cases were included in the study. All tumors showed conventional histopathologic features that are seen in BCCs, but in addition, all the tumors showed large, hyperchromatic, pleomorphic, mononuclear, and multinucleate cells with intracytoplasmic inclusions and intranuclear cytoplasmic invaginations, with rare cases showing stippled nuclei (salt-and-pepper appearance). These histologic features were somewhat concerning for a neuroendocrine carcinoma; thus, immunohistochemistry studies were performed in all cases at the time of diagnosis. By immunohistochemistry, all tumors showed expression of neuroendocrine markers. CD56 was expressed in all cases 24/24, chromogranin was positive in 17/24 cases, and synaptophysin 8/24 was positive in cases. This study confirms a subset of histopathologic features that are present in cases of BCC that are associated with neuroendocrine expression that can potentially be interpreted differently and can create a diagnostic pitfall. Neuroendocrine expression in BCCs is yet uncertain, and further studies are required to fully understand this phenomenon. To avoid diagnostic pitfalls, dermatopathologists must be aware of these unusual histopathologic features and aberrant immunostaining in such tumors; hence, it is advised to perform a thorough histologic inspection.

Mutational Status of NRAS and BRAF Genes and Protein Expression Analysis in a Series of Primary Oral Mucosal Melanoma.

Primary oral mucosal melanoma is an extremely rare and aggressive tumor arising from melanocytes located in the mucosal epithelium of the oral cavity. Although malignant melanoma of oral mucosa shares some clinical features with its cutaneous counterpart, it has been associated with a worst prognosis; its etiopathogenesis are still only partially unraveled as there is no influence of UV radiation. It is known that the mitogen-activated protein kinase pathway mediates cellular responses to growth signals and its activation is an important phenomenon in melanoma. The aim of this study was to evaluate NRAS and BRAF genes, both components of mitogen-activated protein kinase molecular pathway, and compare with their protein expression. Point mutations of NRAS (codons 12, 13, and 61) and BRAF (codon 600) were screened by pyrosequencing method, and its results were associated to the protein expression of RAS and BRAF performed by immunohistochemistry. The authors observed mutation in BRAF 600 (3/14), NRAS codons 12 and 13 (2/14), and NRAS codon 61 (2/8). One case showed positive RAS protein expression, but no mutation was observed. Twelve in 14 cases showed positive BRAF protein expression: 3 cases showed BRAF mutation; 2 cases showed NRAS codon 61 mutation; 2 cases showed NRAS codons 12 and 13 mutation but not simultaneously. Although NRAS and BRAF mutation frequency and RAS protein expression are low, BRAF protein expression was intense; probably, NRAS and BRAF mutations are independent events and alternative molecular mechanisms in the primary oral mucosal melanoma tumorigenesis.

Evaluation of Syringomas by In Vivo Reflectance Confocal Microscopy: A Report of Two Cases.

Syringomas are benign adnexal tumors that are characterized histologically by the presence of small solid and cystic epithelial structures in the upper half of the reticular dermis. Reflectance confocal microscopy is a noninvasive diagnostic method that enables in vivo visualization of tissues with a resolution that approximates that of conventional histopathology. The use of this method in skin imaging over the past several years has improved dermatological diagnoses, creating the potential for its wide application in such diagnoses, especially for benign and malignant skin tumors. We describe its use in the diagnosis of syringoma in 2 patients and correlate the resulting clinical, histopathological, and digital reflectance confocal microscopy images.

Imaging mass spectrometry assists in the classification of diagnostically challenging atypical Spitzoid neoplasms.

BACKGROUND: Previously, using imaging mass spectrometry (IMS), we discovered proteomic differences between Spitz nevi and Spitzoid melanomas. OBJECTIVE: We sought to determine whether IMS can assist in the classification of diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and correlate the IMS and histopathological diagnoses with clinical behavior. METHODS: We conducted a retrospective collaborative study involving centers from 11 countries and 11 US institutions analyzing 102 ASNs by IMS. Patients were divided into clinical groups 1 to 4 representing best to worst clinical behavior. The association among IMS findings, histopathological diagnoses, and clinical groups was assessed. RESULTS: There was a strong association between a diagnosis of Spitzoid melanoma by IMS and lesions categorized as clinical groups 2, 3, and 4 (recurrence of disease, metastases, or death) compared with clinical group 1 (no recurrence or metastasis beyond a sentinel node) (P < .0001). Older age and greater tumor thickness were strongly associated with poorer outcome (P = .01). CONCLUSIONS: IMS diagnosis of ASN better predicted clinical outcome than histopathology. Diagnosis of Spitzoid melanoma by IMS was strongly associated with aggressive clinical behavior. IMS analysis using a proteomic signature may improve the diagnosis and prediction of outcome/risk stratification for patients with ASN.

Desmoplastic melanoma: an updated immunohistochemical analysis of 40 cases with a proposal for an additional panel of stains for diagnosis.

Desmoplastic melanoma (DM) is histologically characterized by a proliferation of spindle melanocytes dispersed in a collagenous stroma that can be mistaken for a variety of neoplasms. The purpose of this study was to analyze 40 cases of DM with a comprehensive panel of immunohistochemical markers (KBA.62, p16, Ezrin, WT-1, MITF-1, SOX-10, CD117, SOX-2, nestin, PNL2, p75, MART-1, gp100 and S100p) to obtain a more complete understanding of the potential use of these antibodies in the diagnosis of DM. We found that all cases of DM expressed p16, WT-1, SOX-10, nestin and S100p and 95% of cases expressed p75. There was variable expression with Ezrin, SOX-2, KBA.62, MART-1 and HMB-45. Most DMs did not express MITF-1, PNL2 and CD117. Conditions that may enter in the histologic differential diagnosis of DM, including dermal scars, fibromatosis and dermatofibromas were also studied. Nearly all control cases also stained positive for p16 but were negative for WT1, SOX10, nestin, p75 and S-100p, as well as for most of the other markers tested. We conclude that a panel of S-100p, WT1, SOX10, p75 and nestin may constitute the optimal panel with the most sensitive and specific combination of immunostain available for the diagnosis of DM.

Actinic Prurigo Cheilitis: A Clinicopathologic Review of 75 Cases.

Actinic prurigo (AP) is a chronic idiopathic photodermatosis that primarily affects American Indians in the United States and Mestizos in Latin American countries. Clinically, the onset of the disease is usually in the first decade of life but may appear initially in adult life, and it is characterized by symmetric involvement of sun-exposed areas of the skin, particularly areas of the face, resulting in polymorphic erythematous papules, macules, and plaques in different stages of evolution. Lower lip involvement includes swelling, scaling, fissures, hyperpigmentation, and ulcerations of the vermilion border. and in some cases could represent the only manifestation of the disease. The histopathologic features of AP have been studied; however, there is a controversy regarding whether AP cheilitis has distinct histopathologic features that could allow accurate separation from other specific and nonspecific forms of cheilitis. The diagnosis can be challenging, mainly when lip lesions are the only manifestation of the disease. In this study, the authors investigate the clinicopathologic features of 75 cases of AP cheilitis to provide further criteria for its diagnosis and classification. All 75 patients presented with lip lesions. Thirty-three cases were diagnosed as AP cheilitis with cutaneous lesions and 42 cases were diagnosed as AP cheilitis without cutaneous lesions (only lip lesions). Histologically, of the 33 cases with AP cheilitis with cutaneous lesions, 17 (52%) cases showed follicular cheilitis, and of the 42 cases that had only lip lesions, 18 (43%) cases showed follicular cheilitis. Histologically, AP cheilitis can present as follicular cheilitis; thus, supporting the diagnosis. Also, our findings confirm that lip lesions can present as the only manifestation of the disease, showing typical histological and clinical features. This form of cheilitis has not being well described in the dermatologic and dermatopathologic literature.

Hydroa vacciniforme-like lymphoma with primarily periorbital swelling: 7 cases of an atypical clinical manifestation of this rare cutaneous T-cell lymphoma.

Hydroa vacciniforme-like lymphoma (HVL) is a rare cutaneous T-cell lymphoma that is usually seen in children of Hispanic or Asian origin. Association between chronic latent Epstein-Barr virus infection in both hydroa vacciniforme (HV) and HVL has been demonstrated and has recently been categorized by the World Health Organization as one of the Epstein Barr virus-positive lymphoproliferative disorders of childhood. Patients with HVL present with a cutaneous rash characterized by edema, blisters, ulcers, and scars mainly seen on the face and extremities that mimic HV; however, unlike in HV, the lesions tend to be extensive and deeper and are associated with severe scarring, necrosis, and systemic manifestations. We are reporting 7 cases of an unusual clinical variant of HVL with primarily periorbital edema. All of our patients in this series presented with progressive periorbital edema that was accompanied with systemic symptoms including fever, malaise, and lymphadenopathy. Most cases were initially misinterpreted as inflammatory processes including cellulitis, arthropod bite reactions, and periorbital lupus erythematosus. The biopsy of these lesions revealed an atypical lymphocytic infiltrate predominantly distributed in the deep dermis and in subcutaneous fat. Immunohistochemistry studies revealed a cytotoxic T-cell (CD8) profile. All cases were associated with Epstein-Barr virus infection. Our study presents a rare clinical variant of HVL with predominant periorbital edema. This variant could potentially be overlooked and misdiagnosed as an inflammatory condition; thus, it needs to be included in the differential diagnosis of periorbital edema in young patients.

Lymphocytic Arteritis in Epstein-Barr Virus Vulvar Ulceration (Lipschütz Disease): A Report of 7 Cases.

Epstein-Barr virus (EBV) infection can rarely present as painful genital ulcers, mostly in young female adolescents. Typically diagnosed by clinical findings, EBV vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all presented with 1 or more painful, punched-out vulvar ulcers. Only patients with acute EBV infection showed other clinical findings: fever and/or atypical lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue, dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis). Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a submucosal scar was found in the eighth specimen. Other histopathologies included venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense angiocentric CD3 CD4 T-cell lymphocyte-predominant infiltrates were found, regionally or diffusely. In 2 specimens, neutrophils compromised half of the infiltrate. Minor components of CD8, CD20, and CD30 lymphocytes, CD123 plasmacytoid monocytes, CD68 macrophages, and plasma cells were present. Small-vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early EBV mRNA (EBER) identified rare solitary or scattered clustered positive lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one EBER positive biopsy. EBV infection has been documented in muscular vessel vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of localized lymphocytic arteritis.

Spindle Cell Atypical Fibroxanthoma: Myofibroblastic Differentiation Represents a Diagnostic Pitfall in This Variant of AFX.

Atypical fibroxanthoma (AFX) is a low-grade, dermal, mesenchymal neoplasm, which lacks a specific lineage of differentiation. The classical histologic appearance of AFX is that of a pleomorphic and spindle cell neoplasm with marked nuclear pleomorphism, mitotic figures, and often prominent storiform pattern that superficially resembles a pleomorphic high-grade sarcoma ("malignant fibrous histiocytoma"). Many histologic variants have been described. We have reviewed 15 cases of AFX characterized by a pure spindle cell morphology that could be easily mistaken for other spindle cell dermal neoplasms. All of our cases were stained with CD68, CD163, CD10, S-100p, p63, wide-spectrum keratin, CD31, CD34, smooth muscle actin (SMA), desmin, calponin, and h-caldesmon. All 15 cases showed an immunoprofile consistent with AFX. In 9 cases, SMA was also strongly expressed; this finding, coupled with the malignant spindle cell histomorphology, can lead to an erroneous diagnosis of cutaneous leiomyosarcoma with potential clinical consequences. Awareness of this pattern of immunoreactivity in this unusual variant of AFX is of importance for avoiding diagnostic misinterpretation. This study intends to characterize the nature and frequency of SMA immunoreactivity in AFX and to discuss the potential diagnostic pitfalls of immunohistochemical markers in distinguishing this entity from other malignant spindle cell neoplasms.

Role of immunohistochemistry in the diagnosis of sebaceous carcinoma: a clinicopathologic and immunohistochemical study.

Sebaceous carcinoma (SC) is a relatively uncommon malignant epithelial neoplasm with a predilection for the periocular region. The diagnosis of SC can be difficult to make at initial presentation, as it can clinically and histopathologically resemble other common benign and malignant epithelial lesions. A diagnosis of SC is made by confirmation of sebaceous differentiation of neoplastic cells, which can often be accomplished by conventional microscopic findings; however, its recognition may be sometimes difficult and requires ancillary studies such as immunohistochemistry (IHC). Many studies have evaluated the role of IHC as a potential technique to differentiate SC from its mimics; however, most of these studies have used a limited panel of antibodies with variable results. The aim of this study was to determine the efficacy of IHC in the diagnosis of SC and to provide some guidelines for interpretation in the diagnosis of these neoplasms. We studied 27 cases of SC with a broad panel of IHC markers using a tissue microarray technique. We also studied 21 control cases of basal cell carcinoma (BCC) and 22 control cases of squamous cell carcinoma (SCC). Representative tissue cores were taken and processed from each case, and the tissue microarrays were stained by standard methods using antibodies to EMA, CK7, Ber-EP4, Factor XIIIA, androgen receptor, p53, adipophilin, progesterone receptor membrane component 1 (PGRMC1), squalene synthase (SQS), and alpha/beta hydrolase domain-containing protein 5 (ABHD5). Our studies show that EMA was expressed in all cases of SC, CK7 was expressed in 24 of 27 cases, Ber-EP4 was expressed in 7 of 27 cases, Factor XIIIA was negative in all cases, androgen receptor was expressed in 9 of 27 cases, P53 was expressed in 12 of 27 cases, adipophilin was expressed in all cases, PGRMC1 was expressed in 22 of 27 cases, SQS was expressed in 11 of 27 cases, and ABHD5 was expressed in 9 of 27 cases. EMA was negative in all cases of BCC, CK7 was expressed in 6 of 21 cases, Ber-EP4 was expressed in 21 of 21 cases, Factor XIIIA was negative in all cases, androgen receptor was expressed in 3 of 21 cases, P53 was expressed in 4 of 21 cases, adipophilin, PGRMC1, SQS, and ABHD5 were negative in all cases of BCC. Similarly, EMA was expressed in 16 of 22 cases of SCC, CK7 was expressed in 2 of 22 cases, Ber-EP4, Factor XIIIA, and androgen receptor were negative in all cases, P53 was expressed in 3 of 22 cases, adipophilin, PGRMC1, SQS, and ABHD5 were negative in all cases of SCC. Our study indicates that adipophilin represents a sensitive and reliable marker for the diagnosis of SC and can be of help in separating this tumor from some of its mimics. Additionally, inclusion of various epithelial markers in the panel will be of help if adequately used. Other antibodies against the PAT family of lipid droplet-associated proteins including PGRMC1, SQS, and ABHD5 were not as sensitive as adipophilin for identifying sebaceous differentiation and may therefore not be as useful for differential diagnosis as adipophilin.