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Benign lichenoid keratosis (BLK) is a cutaneous lesion that can clinically mimic malignancy and may represent regression of a pre-existing lesion. BLK may show epidermal pseudo-nests prompting evaluation for a melanocytic lesion. False positivity of MART-1/Melan-A immunostaining in pseudonests has been showed; however, the value of SRY-related HMG-box 10 (SOX10) staining in BLK with features suspicious for a melanocytic proliferation has not been previously reported.Twenty-one cases of BLK from 2015 to 2020 were identified. Slides were reviewed and SOX10 immunohistochemistry was performed on each case. Subsequently, Melan-A immunohistochemical staining was performed on all cases.In 10 cases (47.6%), unexpected SOX10 staining was seen in rare to numerous small, single cells in the epidermis above the basal cell layer. No malignancy was identified. Of the 10 cases, 8 (80%) showed suprabasal SOX10 staining did not show similar suprabasal Melan-A staining; 2 (20%) cases showed scattered suprabasal cells positive for Melan-A.SOX10 immunostaining in BLK can highlight scattered cells in the epidermis (not easily noticeable on routine stain). Performing SOX10 immunostain alone on BLK can prompt a misdiagnosis of a melanocytic lesion and should be done with caution.

Pathological staging of primary anorectal mucosal melanoma is often performed according to the American Joint Commission on Cancer (AJCC) guidelines for cutaneous melanoma, as an anorectal melanoma-specific staging system does not exist. However, it remains unknown whether prognostic factors derived for cutaneous melanoma also stratify risk in anorectal melanoma. We retrospectively determined correlations between clinicopathological parameters and disease-specific survival in 160 patients. Patients were grouped by clinical stage at presentation (localized disease, regional or distant metastases). Cox proportional hazards regression models determined associations with disease-specific survival. We also summarized the somatic mutations identified in a subset of tumors analyzed for hotspot mutations in cancer-associated gene panels. Most of the patients were white (82%) and female (61%). The median age was 62 years. With a median follow-up of 1.63 years, median disease-specific survival was 1.75 years, and 121 patients (76%) died of anorectal melanoma. Patients presenting with regional (34%) or distant metastases (24%) had significantly shorter disease-specific survival compared to those with disease localized to the anorectum (42%). Of the 71 anorectal melanoma tumors analyzed for hotspot genetic alterations, somatic mutations involving the KIT gene (24%) were most common followed by NRAS (19%). Increasing primary tumor thickness, lymphovascular invasion, and absence of regression also correlated with shorter disease-specific survival. Primary tumor parameters correlated with shorter disease-specific survival in patients presenting with localized disease (tumor thickness) or regional metastases (tumor thickness, absence of regression, and lymphovascular invasion), but not in patients presenting with distant metastases. Grouping of patients according to a schema based on modifications of the 8th edition AJCC cutaneous melanoma staging system stratified survival in anorectal melanoma. Our findings support stage-specific associations between primary tumor parameters and disease-specific survival in anorectal melanoma. Moreover, the AJCC cutaneous melanoma staging system and minor modifications of it predicted survival among anorectal melanoma patients.

Background Melanoma, particularly nevoid melanoma, can masquerade as benign. Helpful differentiating features include nuclear pleomorphism, atypia, prominent nucleoli, absent maturation, and increased mitotic figures. These can be subtle and easily missed unless carefully sought. Thus, the "puffy shirt appearance" concept was born from a Seinfeld episode in which the namesake character unintentionally agreed to wear a pirate-like puffy shirt. Consequently, he found himself out of place, sporting an outfit with "too much shirt in too little space". Similarly, at low-power, nevoid melanoma appears to have "too many cells in too little space". This is more pronounced and easier to appreciate when there is an associated nevus, where crowded, subtly malignant melanocytes stand out from the evenly distributed, more spaced out benign melanocytes. Methods Twelve practicing dermatopathologists familiar with the puffy shirt concept in the context of melanoma were surveyed. Results Hundred percent of participants found it most helpful as a triaging tool, prompting additional work up including higher magnification evaluation, additional levels, consultation, and/or immunohistochemistry. Conclusions The crowded cells in the "puffy shirt appearance" catch the eye and should provoke a more thorough inspection of the lesion. This sign is not pathognomonic for melanoma, but prompts more careful evaluation and helps prevent misdiagnosis.

Post-transplant lymphoproliferative disorder (PTLD) is an uncommon complication after solid-organ transplants and hematopoietic stem cell transplants. Isolated involvement of the skin without systemic involvement in PTLD is extremely rare. Primary cutaneous PTLD is generally categorized as either cutaneous T-cell lymphoma or cutaneous B-cell lymphoma, with variable Epstein-Barr virus (EBV) positivity. Herein, we describe an exceedingly uncommon case of a primary cutaneous Hodgkin-like polymorphic PTLD. A man in his 60s, with a history of kidney transplant, presented with a 5-week history of two indurated plaques. Clinical, histologic and immunohistochemical findings were consistent with primary cutaneous Hodgkin-like polymorphic PTLD. Reduction in immunosuppression led to resolution of his lesions. This case highlights a rare case of primary cutaneous Hodgkin-like PTLD and increases awareness of this uncommon post-transplant complication. It also underscores the importance of collaboration between dermatology, hematology, dermatopathology and hematopathology in order to diagnose challenging cases.

A 51-year-old white woman with a past medical history significant for steroid-dependent ulcerative colitis, rheumatoid arthritis, and diabetes mellitus presented to the hospital with fever and painful, erythematous subcutaneous nodules on the medical aspects of both thighs. Histopathologic examination showed features suggestive of an abscess, but her condition failed to improve with intravenous broad-spectrum antibiotics. Molecular studies detected T cell receptor-β gene rearrangements. The lesions later exhibited signs of necrosis, requiring multiple debridements as well as therapy with hyperbaric oxygen. She was later referred to the MD Anderson Cancer Center for evaluation for possible subcutaneous panniculitis-like T cell lymphoma.

Checkpoint inhibitors (CPIs) restore the function of effector immunocytes to target and destroy cancer cells. Immune-related adverse events (irAEs) are a consequence of immune reactivation, with unpredictable inflammatory response, loss of self-tolerance, and development of autoimmunity. Adverse events from CPIs that present as dermatologic toxicities have diverse clinical and histopathologic features. CPI-associated dermatologic toxicities may exhibit histopathologic features of lichenoid dermatitis, bullous pemphigoid, and granulomatous/sarcoid-like reactions. Suprabasal acantholytic dermatologic toxicities associated with CPIs are particularly rare but represent an emerging histopathologic pattern and include lichenoid dermatitis with suprabasal acantholysis/vesicle formation to Grover disease (transient acantholytic dermatosis). Here, we report two patients who developed suprabasal acantholytic dermatologic toxicities during CPI therapy. One patient exhibited a CPI-associated autoimmune blistering disease with paraneoplastic pemphigus (PNP)-like features restricted to histopathology and immunofluorescence, while the other patient had Grover-like lesions. A review of the literature revealed a spectrum of suprabasal acantholytic dermatologic toxicities associated CPIs that may present as lichenoid dermatitis with acantholysis/vesicle formation, Grover-like eruptions, and lesions with PNP-like features restricted to histopathology and immunofluorescence. It is important for clinicians and pathologists to recognize the types of dermatologic toxicities associated with CPIs to direct appropriate therapeutic strategies.

Background The Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group recently published a consensus statement that incompletely excised moderately dysplastic nevi (MDN) without clinical residual pigmentation can be observed and not re-excised. However, data regarding recurrence of MDN with positive histologic margins are quite scant. Objective We sought to extend the reported findings with a study to determine the recurrence rate of MDN with positive histologic margins. Methods We performed a retrospective study on MDN with positive histologic margins that were not re-excised and for which at least 1 year of clinical follow-up was available. Results We found a total of 147 such nevi from January 1, 2007, to December 31, 2013. Six MDN (5 compound and 1 junctional) or 4% recurred with an average recurrence time of 1.7 years. All of these MDN were evaluated by shave biopsies. Limitations Subjectivity in grading of atypia is a limitation of this study. Conclusion These data from a large study focusing exclusively on recurrence of MDN with positive histologic margins support the conclusion of the Pigmented Lesion Subcommittee that incompletely excised MDN do not require re-excision.

Radiation therapy is a mainstream strategy in the treatment of several cancer types that are surgically unresectable. Unfortunately, cancer patients often suffer from unintended consequences of radiotherapy, including the development of skin inflammation (dermatitis), which may progress to fibrosis. These morbid complications often require interruption of radiotherapy and threaten the relapse of underlying cancer. Current treatment options for radiation dermatitis are suboptimal and compel the need to develop safer, more effective therapies. In this study, we assessed the biophysical properties of topically-formulated esomeprazole (here referred to as dermaprazole) and performed proof-of-concept studies to evaluate its efficacy in vitro and in vivo. We found that dermaprazole induced nuclear translocation of erythroid 2-related factor 2 (Nrf2) and significantly upregulated heme oxygenase 1 (HO1) gene and protein expression in a 3D human skin model. Our animal study demonstrated that dermaprazole improved macroscopic appearance of the irradiated skin and accelerated healing of the wounds. Histopathology data corroborated the photographic evidence and confirmed that both prophylactically and therapeutically administered dermaprazole conferred potent anti-inflammatory and antifibrotic effects. Gene expression data showed that dermaprazole downregulated several pro-oxidant, pro-inflammatory and profibrotic genes. In conclusion, topical formulation of the FDA-approved drug esomeprazole is highly effective in attenuating dermal inflammation and fibrosis.

Pathological staging of primary anorectal mucosal melanoma is often performed according to the American Joint Commission on Cancer (AJCC) guidelines for cutaneous melanoma, as an anorectal melanoma-specific staging system does not exist. However, it remains unknown whether prognostic factors derived for cutaneous melanoma also stratify risk in anorectal melanoma. We retrospectively determined correlations between clinicopathological parameters and disease-specific survival in 160 patients. Patients were grouped by clinical stage at presentation (localized disease, regional or distant metastases). Cox proportional hazards regression models determined associations with disease-specific survival. We also summarized the somatic mutations identified in a subset of tumors analyzed for hotspot mutations in cancer-associated gene panels. Most of the patients were white (82%) and female (61%). The median age was 62 years. With a median follow-up of 1.63 years, median disease-specific survival was 1.75 years, and 121 patients (76%) died of anorectal melanoma. Patients presenting with regional (34%) or distant metastases (24%) had significantly shorter disease-specific survival compared to those with disease localized to the anorectum (42%). Of the 71 anorectal melanoma tumors analyzed for hotspot genetic alterations, somatic mutations involving the KIT gene (24%) were most common followed by NRAS (19%). Increasing primary tumor thickness, lymphovascular invasion, and absence of regression also correlated with shorter disease-specific survival. Primary tumor parameters correlated with shorter disease-specific survival in patients presenting with localized disease (tumor thickness) or regional metastases (tumor thickness, absence of regression, and lymphovascular invasion), but not in patients presenting with distant metastases. Grouping of patients according to a schema based on modifications of the 8th edition AJCC cutaneous melanoma staging system stratified survival in anorectal melanoma. Our findings support stage-specific associations between primary tumor parameters and disease-specific survival in anorectal melanoma. Moreover, the AJCC cutaneous melanoma staging system and minor modifications of it predicted survival among anorectal melanoma patients.

Cowden Syndrome (CS) is an uncommon autosomal dominant multiorgan/system genodermatosis. It is characterized by the development of multiple hamartomas of endodermal, mesodermal and ectodermal origin, an increased lifetime risk of breast, thyroid, endometrial, and other cancers and an identifiable germline mutation. Mucocutaneous hamartomas are the most common lesions seen and mainly include facial trichilemmomas, oral mucosal papillomas, and benign acral keratoses. Herein, we report a case of a 63-year-old Caucasian male with a long-established diagnosis of CS and history of thyroid cancer, colonic polyps, and innumerable trichilemmomas, seborrheic keratoses, squamous papillomas, and non-melanoma skin cancers excised in the past. He presented in four separate occasions with small skin-colored papulonodular lesions that upon excision revealed to be clear cell acanthomas. He also developed a tumor in the preauricular area that was completely resected and was found to be a sebaceous lymphadenoma of the parotid gland. This is to our knowledge, the second report of clear cell acanthoma and also the second reported case of sebaceous lymphadenoma in a patient with CS.

Digital papillary adenocarcinoma is a rare malignant tumor of the sweat glands, most commonly encountered in adult males. Only few pediatric cases have been reported, with an apparent predominance of females and none on the ankle. We report a case of a 15-year-old girl with a slowly growing, non-tender mass on the right ankle presenting with difficulty in walking; clinically believed to be a keloid. Excision of the mass revealed a glandular neoplasm with largely eccrine and focally apocrine differentiation. Histologic features do not reliably predict biologic behavior. Because of the existing confusion over the nomenclature, we propose that such tumors be called 'papillary adnexal neoplasms of distal extremities'.

Background: Anorectal melanoma (AM) is generally staged using criteria developed and validated for cutaneous melanoma (CM), primarily due to its rarity and the lack of a specific staging system, despite limited evidence to support this. In an attempt to risk-stratify AM patients (pts), we analyzed the performance of the AJCC 8th edition CM staging system and a system recently developed for vulvar melanoma (VM) in a retrospective cohort. Methods: Demographics, clinicopathologic factors, and follow-up information were collected for 160 AM pts treated at our institution. The pts were grouped based on their clinical stage at presentation (localized to anorectum [L], regional metastases [R], distant metastases [D]). For further risk stratification, L pts were grouped according to the following systems: (i) AJCC 8th edition CM T-categories (T1a to T4b, 8 tiers); (ii) AJCC 8th edition CM stage (I vs. II, 2 tiers); (iii) the tumor thickness (TT) system (thin [T1], intermediate [T2-T3], thick [T4], 3 tiers); and TM system previously derived for VM (T1: TT≤ 2.0mm and mitotic rate (MR) 2.0mm and MR Results: The cohort (n=160) included 67 L, 55 R and 38 D pts. With median follow-up of 1.63 years (y), the median DSS was 1.75y for all pts. DSS progressively decreased according to stage at presentation (L: 2.39y; R: 1.81y and D: 1.25y). By UV analysis, clinical stage at presentation correlated with DSS (R: p=0.05, HR=1.52; D: p Conclusion: Clinical stage at presentation and T-categorization of L pts based on modifications of the 8th edition AJCC CM staging criteria (stage and TT system) appear to be potentially informative tools to stratify risk in AM pts. Citation Format: Priyadharsini Nagarajan, JIn Piao, Jing Ning, Laura E. Noordenbos, Jonathan L. Curry, Carlos A. Torres-Cabala, A. Hafeez Diwan, Phyu P. Aung, Doina Ivan, Merrick I. Ross, Richard E. Royal, Jennifer A. Wargo, Wei-Lien Wang, Rashmi Samdani, Alexander J. Lazar, Asif Rashid, Michael A. Davies, Victor G. Prieto, Jeffrey E. Gershenwald, Michael T. Tetzlaff. Prognostic model for disease-specific survival in anorectal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A11.

We present the case of a 33-year-old female who developed a cystic nodule on the vulva during pregnancy. Immediately following Cesarean section, the lesion was biopsied and histologic examination revealed a dermal tumor composed of glandular structures arranged in a labyrinth pattern. The glandular structures displayed cytoplasmic vacuolization, large atypical nuclei, prominent nucleoli and scattered eosinophilic luminal secretions. Immunohistochemistry showed the tumor cells to be diffusely positive for CK7 and progesterone receptor with focal expression of mammaglobin and GCDFP-15. The tumor cells were negative for estrogen receptor and CK20. These histologic and immunophenotypic findings were consistent with hidradenoma papilliferum. Our unusual (and to our knowledge first reported) case demonstrates hidradenoma papilliferum in association with pregnancy and raises the possibility of cytologic atypia and lactational change being secondary to hormonal changes in pregnancy.

Linear IgA bullous dermatosis is a rare autoimmune vesiculobullous disease characterized by linear deposition of IgA along the basement membrane zone. It is classically idiopathic, but may also arise secondary to drug exposure. A heterogeneous spectrum of clinical features has been described, including a rare, morbid variant mimicking toxic epidermal necrolysis. Herein, we present a case of vancomycin-induced linear IgA bullous dermatosis that manifested clinically as toxic epidermal necrolysis and resolved with dapsone therapy.

Melanocytic nevi can undergo clinical and histopathologic changes during pregnancy, as well as after various forms of surgical and nonsurgical trauma. We report the case of a 9-month postpartum 29-year-old female who presented to her dermatologist with a clinically worrisome nevus. This nevus had been treated with liquid nitrogen by her primary care physician 6 months prior to presentation. Histopathologic evaluation revealed a crowded proliferation of atypical melanocytes at the dermal-epidermal junction overlying a scar. The dermal component contained scattered mitotic figures. A combined MART-1, tyrosinase and Ki-67 immunohistochemical study showed foci of increased melanocytic proliferation. These atypical features were interpreted as associated with both the prior cryotherapy, as well as her recent pregnancy. Knowledge of the clinical context in evaluating difficult melanocytic lesions is essential.

Cutaneous carcinosarcoma (CCS) is an extraordinarily rare neoplasm with a biphasic morphological pattern exhibiting both epithelial and sarcomatoid components. Although its histogenesis and biological aspects remain poorly understood, previous studies have postulated that this tumor may arise from single cancer stem cells which subsequently differentiate into distinct tumor lineages. In this study, we explored a wide array of mutational hot spot regions, through high-depth next-generation sequencing of 47 cancer-associated genes in order to assess the mutational landscape of these tumors and investigate whether the epithelial and mesenchymal components shared the same genetic signatures. Results from this study confirm that despite their striking phenotypic differences, both elements of this infrequent tumor indeed share a common clonal origin. Additionally, CCS appears to embrace a heterogeneous spectrum with specific underlying molecular signatures correlating with the defining epithelial morphotype, with those carcinosarcomas exhibiting a squamous cell carcinoma epithelial component exhibiting diverse point mutations and deletions in the TP53 gene, and those with a basal cell carcinoma morphotype revealing a more complex mutational landscape involving several genes. Also, the fact that our findings involve several targetable gene pathways suggests that the underlying molecular events driving the pathogenesis of CCS may represent future potential targets for personalized therapies.

Pleomorphic fibromas represent dome-shaped or polypoid cutaneous lesions characterized by a paucicellular and densely fibrotic background punctuated by scattered atypical to pleomorphic spindle and multinucleated giant cells. Some of these tumors will have incorporated adipose tissue, although these adipocytic areas lack distinct cytologic atypia and may represent entrapped normal periadnexal or subcutaneous adipose tissue. Nonetheless, owing to the similarity of some of the morphologic features of pleomorphic fibroma with cutaneous atypical lipomatous tumor, diagnostic confusion can ensue. The potential diagnostic challenges are further highlighted by a recent report of a lesion with histopathologic features of both. In response, we studied the presence of 12q15/ MDM2 amplification by fluorescence in situ hybridization and MDM2 expression by immunohistochemistry in a series of 15 pleomorphic fibromas to investigate whether these two entities share a common pathogenic origin. One case of cutaneous atypical lipomatous tumor was used as positive control for 12q15 amplification. All 15 cases were negative for MDM2 by immunohistochemistry with no demonstrable 12q15/MDM2 amplification by fluorescence in situ hybridization. Therefore, these two entities are best regarded as pathogenetically distinct. MDM2 immunohistochemistry or fluorescence in situ hybridization studies can be used to differentiate between the two if needed.

Digital papillary adenocarcinoma is a rare malignant tumor of the sweat glands, most commonly encountered in adult males. Only few pediatric cases have been reported, with an apparent predominance of females and none on the ankle. We report a case of a 15-year-old girl with a slowly growing, non-tender mass on the right ankle presenting with difficulty in walking; clinically believed to be a keloid. Excision of the mass revealed a glandular neoplasm with largely eccrine and focally apocrine differentiation. Histologic features do not reliably predict biologic behavior. Because of the existing confusion over the nomenclature, we propose that such tumors be called 'papillary adnexal neoplasms of distal extremities'.

Background Assessment of histologic and immunohistochemical maturation (with HMB-45 and anti-Ki-67) may be helpful in differentiating benign melanocytic nevi (BMN) from malignant melanoma. Recently, we reported loss of maturation and aberrant immunohistochemical findings in melanocytic nevi after liquid nitrogen cryotherapy (Adeniran et al, J Am Acad Dermatol 2009;61:341-5). Herein we report a similar phenomenon identified in traumatized melanocytic nevi (TMN). Objective We sought to evaluate the histologic and immunohistochemical findings in early and late stages of traumatized nevi. Methods Twenty-four cases of TMN were retrieved from the pathology archives. These were then assessed by two pathologists (T.L. and A.H.D.) using HMB-45 and MIB-1 (for Ki-67) antibodies. Results TMN showed some of the following findings: epidermal changes (parakeratosis, ulceration, serum crust, flattening of the epidermis) and dermal changes including fibrosis and the presence of melanophages. In some cases, there was architectural disorder of the overlying melanocytes, with crowding in the basal layer, but without significant pagetoid spread. Occasionally, the dermal scar contained larger, more epithelioid-appearing melanocytes than those beneath the scar. Fifty-four percent of TMN lacked obvious immunohistochemical maturation with HMB-45, since nevus cells within the scar or directly beneath it were strongly labeled. None of the TMN showed appreciable labeling for Ki-67. Limitations The exact clinical duration between trauma and biopsy could not be determined. Conclusion Loss of maturation with HMB-45 in TMN can be a diagnostic pitfall in challenging cases. Concurrent evaluation of MIB-1 expression, along with the characteristic histologic features of trauma, should allow the correct diagnosis to be reached.

Leuprolide acetate represents a gonadotropin-releasing hormone agonist, used as part of the treatment of prostate cancer. We report an unusual case of disseminated urticarial rash following leuprolide injection in a 67-year-old man that histopathologically and immunohistochemically resembled mycosis-fungoides, including the presence of follicular mucinosis and eosinophils in the follicles. This histopathologic pattern has not been previously described as a drug reaction pattern due to leuprolide, and it underscores the importance of correlation with the clinical impression to arrive at a correct diagnosis.

Cutaneous leishmaniasis is rarely seen in the United States. Four Cuban immigrants traveled along the same route at different times from Cuba to Ecuador, then northward, including through the Darién Jungle in Panama. These patients had chronic ulcerative non-healing skin lesions and were given a diagnosis of leishmaniasis.

PURPOSE To report the clinical and histopathologic features in 6 patients with cutaneous melanoma metastatic to the eyelid and periocular skin. METHODS Clinical records and radiographic features of all consecutive patients treated by the principal investigator between January 2005 and October 2007 with the diagnosis of cutaneous melanoma metastatic to the eyelid and periocular skin. RESULTS Six patients ranged in age from 26 to 84 years old (median, 55 years). Five patients had their metastatic lesion in the upper eyelid and 1 in the lower eyelid. The mean survival after the diagnosis of melanoma metastatic to the eyelid was 5.3 months. All patients had metastases at other sites detected prior to the diagnosis of the eyelid metastasis. The mean interval from initial primary tumor diagnosis to metastasis to the eyelid was 121 months. In all 6 patients, palliative surgical resection of the metastatic eyelid lesions was carried out. CONCLUSIONS Melanoma metastatic to the eyelid is not uncommon in advanced stage cutaneous melanoma. Palliative surgical management of these metastatic lesions should be considered to improve the patient's quality of life.

Using immunohistochemistry with anti-D2-40 for the detection of lymphovascular invasion (LVI-IHC) in 74 cases of invasive melanoma, we found LVI in 23% (16/74) of the tumors. Data on sentinel lymph node (SLN) biopsy were available for 36 patients. Sixty-seven percent (6/9) of patients with LVI-IHC and 19% (5/27) without LVI-IHC had positive SLN. Follow-up data were available for 60 patients. Data on recurrence/metastasis were available for 60 patients. Twenty-five percent (15/60) had LVI with immunohistochemistry. Fifty-three percent (8/15) of these patients had “distant” metastasis or regional recurrence compared with 11% (5/45) in those without LVI-IHC. Overall and disease-specific survival was shorter for patients with LVI. In both the univariate and multivariate Cox proportional hazards regression models, LVI-IHC in addition to ulceration was statistically significant with respect to overall survival. Specifically, in the reduced multivariate model, compared with patients with no LVI, patients with intratumoral LVI had a hazard ratio (HR) of 5.4 (95% CI 1.6–18.4), while patients with peritumoral LVI had a HR of 3.8 (95% CI 0.7–20.9). In addition, patients with ulceration had an increased hazard of 4.4 (95% CI 1.2–16.8). For the first time, we herein show a positive correlation with LVI in melanoma detected with immunohistochemistry and distant metastasis, overall survival and disease-free survival.

Clusterin expression is common in systemic and cutaneous anaplastic large cell lymphoma (ALCL). Mycosis fungoides (MF) in large cell transformation can resemble ALCL. In this study, we immunohistochemically assessed for clusterin in 97 skin biopsy specimens, including 70 MF cases and 27 other cutaneous neoplasms including ALCL, peripheral T-cell lymphoma unspecified (PTCL), and lymphomatoid papulosis (LyP). Clusterin was positive in 36 (51%) of 70 cases of MF and correlated with clinical stage in 68 cases: 3 of 21 stage I, 11 of 20 stage II, and 23 of 27 stage III/IV. Clusterin expression also correlated with type of skin lesion (3/19 patch, 13/28 plaque, and 20/23 tumor/erythroderma) and number of large cells (6/30 small cell, 12/18 with increased large cells, and 18/22 with large cell transformation). Clusterin expression was not specific for MF as it also was positive in 3 of 3 cases of LyP, 2 of 2 systemic ALCL cases involving skin, 7 of 16 cutaneous ALCLs, and 1 of 6 PTCLs.

Epithelioid cell histiocytoma (ECH) is a variant of dermatofibroma that presents typically as a solitary nodule. We report a case of a 20-year-old male who presented with a bleeding nodular lesion on the left arm followed a month later by a nodule on the right nostril. Both lesions had epithelioid cells in the dermis, with focal Factor 13a and CD68 immunoreactivity. The left arm lesion, in addition, showed staghorn vasculature as well. Both lesions were interpreted as ECH. The patient had an unremarkable medical history. To the best of our knowledge, multiple ECHs have not been reported in the literature. An appropriate diagnosis of ECH is important as the differential diagnosis usually includes melanocytic lesions.

According to most authors, dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) represent the adult and juvenile forms, respectively, of the same disease entity, as evidenced by similar morphology, an identical chromosomal translocation, and CD34 positivity. It has been shown that DFSP and nuchal-type fibroma (NTF) (which is also CD34-positive) are related lesions, and that there might possibly be a continuum between the two. In addition, NTF exhibits CD99 positivity. It was therefore, hypothesized that both DFSP and GCF would show similar immunopositivity for CD99. Archives of pathology at several institutions were searched for DFSP and GCF tissue blocks. A total of 29 DFSP and 5 GCF were analyzed by immunohistochemistry for expression of CD99. Twenty-three of 29 DFSP (79%) and 2 of 5 GCP (40%) expressed CD99. Comparison of CD99 and CD34 showed that the non-tumoral periphery of DFSP was less probable to be CD99 positive, but this finding was not statistically significant.

Cutaneous sebaceous neoplasia is known to exhibit a high degree of DNA mismatch repair (MMR) deficiency leading to microsatellite instability and these tumors can be markers of the Muir-Torre syndrome and internal malignancy. Other tumors, such as colonic carcinoma, show tendencies toward particular histologic features and sites of involvement correlating with MMR deficiency. There are few comprehensive studies of unselected cutaneous sebaceous neoplasms. To address this gap in knowledge, we examined 94 sebaceous neoplasms from 92 patients and 17 sebaceous hyperplasia controls using immunohistochemistry for MLH1, MSH2, and MSH6. Our results indicate that MMR deficiency is significantly associated with anatomic location (more frequently in the trunk and extremities as compared with head and neck), tumor type (more often in adenoma compared with carcinoma within the head and neck region), and architecture (keratoacanthomalike). No correlation between cystic change and MMR deficiency was noted. Cutaneous sebaceous neoplasia has tendencies toward certain tumor types and anatomic distribution based on MMR status analogous to that seen in colonic carcinomas and other tumors. These may be helpful indicators for further workup for the Muir-Torre syndrome.

Basal cell carcinoma is the most common malignancy in Caucasian individuals. Metastatic basal cell carcinoma is extremely rare (with a rate estimated as 0.03%). Actin has been detected in aggressive forms of basal cell carcinoma, but their expression in metastatic lesions is not known. We compared the expression of actin and actin-related cytoskeletal proteins in relatively less aggressive basal cell carcinoma (nodular), aggressive basal cell carcinoma (infiltrative/morpheaform), and metastatic basal cell carcinoma. We studied 12 cases of nodular basal cell carcinoma, 10 cases of infiltrative basal cell carcinoma, and 10 cases of metastatic basal cell carcinoma with immunohistochemistry for alpha-smooth muscle actin, calponin, myosin, and E-cadherin. Expression was interpreted as positive when at least 5% of the tumor exhibited at least weak expression. Five of the ten patients with metastatic basal cell carcinoma had an antecedent history of radiotherapy. Actin was present in 3 of 12 (25%) of the nodular, all 10 of the infiltrative, and 3 of 10 of the metastatic basal cell carcinomas (P

p63, a recently identified homologue of the p53 gene, is mainly expressed by basal and myoepithelial cells in skin. Others and we have shown the value of p63 in distinguishing primary adnexal tumors from visceral adenocarcinomas metastatic to skin. We now investigate the pattern of p63 expression in metastases from skin adnexal carcinomas and their cognate primaries and evaluate p63 expression in a larger case series of malignant cutaneous adnexal neoplasms. Immunohistochemical analysis for p63 was performed on 13 metastases of adnexal carcinomas and their corresponding primary tumors. Twenty visceral metastatic adenocarcinomas to the skin and 7 primary mucinous carcinomas with cutaneous or visceral origin were compared. The majority (90.9%) of primary adnexal tumors strongly expressed p63 and their metastases labeled similar to their cognate primary tumors. With one exception, primary or metastatic mucinous carcinomas did not express p63. Metastases from two apocrine carcinomas lacked p63 expression. All other cutaneous metastases from internal adenocarcinomas were negative for p63. Analysis of p63 expression may assist in the differential diagnosis of primary adnexal carcinomas versus metastatic visceral adenocarcinomas to the skin. Metastases from adnexal carcinomas generally retain p63 expression similar to their associated primary tumors.

Renal cell carcinoma marker (RCC-Ma) is a monoclonal antibody against a normal renal proximal tubule antigen. RCC-Ma expression is relatively specific for primary clear cell renal cell carcinoma. Its expression in cutaneous metastasis of renal cell carcinoma (MRCC) and other cutaneous clear cell lesions has not been studied.One hundred and thirty-seven cutaneous clear cell lesions including eight xanthomas, 32 xanthelasmas, 25 xanthogranulomas, seven balloon cell nevi, six clear cell hidradenomas, 29 sebaceous adenomas, six sebaceous epitheliomas, eight sebaceous carcinomas, and 16 MRCC were examined using immunohistochemistry for the expression of RCC-Ma.RCC-Ma was expressed in 10 of 16 (62.5%) MRCC, all with greater than 20% of cell labeling. Of these, 4 of 10 (40%) labeled with a membranous pattern and 6 of 10 (60%) labeled with both a membranous and a cytoplasmic pattern. RCC expression was not seen in any of the other clear cell lesions (p0.001). Furthermore, lack of expression in each of the other diagnostic groups was significant when each group was compared with the MRCCs (p0.01 at least for each group).Our study demonstrates that RCC may be a valuable component of a panel of immunohistochemical markers when evaluating cutaneous clear cell lesions.

Background: Although various studies have stressed the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-PI3K-AKT pathway in the progression of melanocytic lesions, little is known about the expression pattern of PI3K in these lesions. Objective: To investigate the expression pattern of PI3K in benign and dysplastic nevi, primary melanomas, and metastatic melanomas and the role of PTEN and PI3K in melanocytic tumor progression. Methods: Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 89 melanocytic lesions: 17 benign nevi, 18 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. Expression of PTEN and PI3K (p85 and p110 subunits) was evaluated immunohistochemically, and the number of cells and labeling intensity were assessed semiquantitatively. Results: Both benign and dysplastic nevi showed strong cytoplasmic staining with PTEN, which was subsequently less in melanomas and completely lost in the metastatic lesions. Eleven of 17 (64%) benign nevi, seven of 10 (70%) dysplastic nevi, four of 23 (17%) primaries, and one of 31 (3%) visceral or lymph node metastasis showed strong positivity. Loss of PTEN expression from benign and dysplastic nevi to melanoma was statistically significant (p = 0.001). Although few cells showed reactivity for phosphoinositide 3-kinase (PI3 kinase)-p85 subunit, strong positivity was not detected in the cytoplasm of benign, malignant, or metastatic lesions, except for a single visceral metastasis. Three of 13 (23%) nevi showed positivity for the p110 subunit. No positivity was observed in the dysplastic nevi. Two of 22 (9%) melanomas, one of 14 (7%) visceral metastasis, and three of 12 (25%) lymph node metastasis showed strong positivity. There was no statistical difference in PI3 kinase expression in benign and malignant melanocytic lesions (p = 0.2). Conclusion: PI3K is not overexpressed in melanocytic lesions.

We assessed the feasibility of using high-frequency ultrasound biomicroscopy (UBM) in estimating thickness of conjunctival melanomas preoperatively. Three patients underwent UBM prior to excision of conjunctival melanoma between February 2003 and March 2006. Conjunctival tumor thickness was estimated via UBM in each case and compared with the estimated histopathologic tumor thickness (Breslow thickness). Patient 1 had an estimated thickness of 1.99 mm via UBM versus a Breslow thickness measurement of 1.5 mm based on the surgical specimen. Patient 2 had a UBM thickness measurement of 2.4 mm and a Breslow thickness of 2.23 mm based on the surgical specimen. In patient 3, both UBM thickness and Breslow thickness were 2.3 mm. The use of high-frequency UBM is feasible for the estimation of tumor thickness for conjunctival melanomas. UBM may serve as an additional diagnostic tool for estimating tumor thickness before surgical resection of conjunctival melanoma. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007

We report the association of common variable immunodeficiency syndrome with epidermodysplasia verruciformis (EV) manifesting as flat warts and squamous cell carcinomas in a 21-year-old Hispanic woman. Human papillomavirus (HPV) typing by polymerase chain reaction using an EV-HPV primer system, cloning, and sequencing detected HPV-8 and HPV-23 DNAs in the biopsy sample. Our case is the second reported case of common variable immunodeficiency syndrome associated with EV.

We have reported a high prevalence of hypothyroidism in the cutaneous melanoma population, suggesting that the pathologic hormonal environment of hypothyroidism promotes melanoma growth. The objective of this study was to test the hypothesis that TSH, which circulates at elevated levels in hypothyroid individuals, stimulates the growth of melanoma cells. Our results show that TSH receptors (TSHR) are expressed by virtually all cutaneous melanocytic lesions, including benign nevi, dysplastic nevi, and melanomas, with higher expression found in malignant and pre-malignant lesions. The finding of TSHR expression by human tumors is confirmed in cultured melanoma cells and melanocytes, in which TSHR expression is demonstrated by immunofluorescent staining, western blotting, and reverse transcriptase-PCR. Melanoma TSHR are functional, as evidenced by the ability of TSH to induce the formation of cAMP and to activate the mitogen-activated protein kinase (MAPK) pathway. Cultured melanoma cells, but not melanocytes, are induced to proliferate at a physiologically relevant concentration of TSH. Taken together, these data support the hypothesis that TSH is a growth factor for human melanoma. Our findings have broad clinical implications for the prevention of melanoma and the management of established disease.

Angiosarcoma is a rare, aggressive, malignant endothelial neoplasm with a variable clinical presentation. The authors describe a case of angiosarcoma involving the eyelid that was complicated by a superimposed Enterobacter infection. Following positive cultures for E. aerogenes and multiple biopsies suspicious but not definitive for angiosarcoma, a final biopsy was consistent with angiosarcoma.

Different criteria have been used to define giant basal cell carcinoma (BCC). However, the majority of tumors of 10 cm or greater in diameter have a characteristic clinical and histopathologic presentation. As a group, these tumors often show metastatic spread as opposed to all other BCCs that rarely metastasize. We present an additional patient with a giant BCC greater than 100 cm2. This tumor had a characteristic location and infiltrative growth pattern. Unusual features of this tumor included a lack of expression of BCL-2 with a greater proportion of cycling tumor cells expressing proliferation markers than conventional BCC, as well as expression of anogenital human papillomaviruses (HPV) subtypes with oncogenic potential. The association of HPV with BCCs has rarely been studied and may not be identical to HPV-induced genital squamous cell carcinomas. However, the findings in this patient suggest that HPV may play a role in the development of some chronic giant BCCs.

Background: Dermatofibrosarcoma protuberans (DFSP) is a hypercellular, storiform, CD34-positive low-grade sarcoma with honeycomb entrapment of fat, which typically involves the trunk and extremities. Nuchal-type fibroma (NTF ) is a paucicellular, CD34-positive fibrous tumor with fat entrapment, which may occur in both nuchal and extranuchal locations and in association with Gardner syndrome. Methods: We report the association of DFSP with NTF in a 43-year-old male with no personal or family history of Gardner syndrome. Results: The patient had a past history of a DFSP removed from his back, which recurred 2 years later and was re-excised. Additionally, the patient had a typical NTF, in the posterior neck, removed at the same time. Histopathologic examination of the recurrent back lesion demonstrated a composite lesion with typical appearances of DFSP, centrally, blending into an NTF-like appearance, peripherally. Both components expressed CD34 and CD99, and lacked elastin. A review of the microscopic slides of the patient's previously excised DFSP revealed an identical lesion with surrounding NTF-like areas. Conclusion: While an association between NTF and fibromatosis has recently been reported, this is to our knowledge the first report of an association between NTF and DFSP. The morphologic findings suggest that there may be a continuum between these two CD34-positive lesions that have a tendency to infiltrate adipose tissue and recur.

Background: Insulin-like growth factor-1 (IGF-1) is one of the most critical proteins required for the survival, migration, and growth of melanoma cells. IGF-binding protein 2 (IGFBP2), which binds and regulates the function of IGF-1, is upregulated in a dose-dependent manner in melanoma cells treated with IGF-1, suggesting a possible role of IGFBP2 in the pathogenesis of melanoma. Methods: Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 94 melanocytic lesions: 20 benign nevi, 20 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. IGFBP2 expression was evaluated immunohistochemically using a polyclonal antibody against the C-terminus of IGFBP2. The number of cells and labeling intensity were assessed semiquantitatively. Results: Positive IGFBP2 labeling was observed in 5.0% of benign nevi, which was significantly lower than in dysplastic nevi (35.0%), primary melanomas (52.2%), or metastatic melanomas (54.8%) (p

Background: Nevus sebaceus (NS) of Jadassohn is a common congenital lesion associated with numerous benign and malignant tumors. However, mucoepidermoid carcinoma (MEC) has not been described in association with NS. Methods: We describe an unusual case of MEC arising within NS. Results: A 72-year-old man presented with an enlarging plaque on his forehead, along the hairline. Physical examination revealed a mounded, erythematous lesion that was completely excised. Histological evaluation revealed a typical MEC with areas of squamous and adenomatous differentiation with foci of typical intermediate cells. Conclusion: The diagnosis of MEC is an important one, because it portends a poor prognosis, requiring long follow-up. This is, to our knowledge, the first report of MEC arising within NS.