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Background: Histopathologic overlap between cutaneous squamous cell carcinoma (cSCC) and its indolent mimics likely leads to the overdiagnosis of cSCC., Objective: To perform a pilot study of the p53 immunohistochemical scoring system developed on vulvar squamous lesions in cSCC., Methods: The consistency and reliability of p53 immunostaining using a scoring system developed on vulvar cases, as compared with TP53 genomic sequencing, was studied in an initial cohort of 28 cutaneous cases. p53 labeling was further assessed in an additional 63 cases of atypical squamous lesions, including 20 atypical squamous lesions classified by the authors as benign, 22 cases diagnosed as cSCC without high-risk features, and 21 cases of high-risk cSCC (cSCC-HR)., Results: The concordance of p53 labeling and TP53 sequencing was 82.1%. Four positive patterns of p53 mutation were identified: basal, parabasal/diffuse, null, and cytoplasmic. p53 positivity in atypical, benign squamous lesions (10%) was significantly lower than that of low-risk cSCC (63.6%, p = 0.0004) or cSCC-HR (90.5%, p < 0.0001). p53 positivity in low-risk cSCC versus cSCC-HR was not statistically significant (p = 0.07)., Conclusion: p53 Labeling may be a helpful biomarker to support the diagnosis of cSCC and distinguish cSCC from atypical but benign mimics., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Abstract: Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used to facilitate distinction of benign and malignant melanocytic proliferations. We hypothesized that evaluation of 1 institution's experience with PRAME labeling in a large number of consecutive cases might elucidate additional strengths and potential pitfalls and reveal base rates of positivity versus negativity in 1 academic practice. Pathology reports for all specimens on which PRAME labeling was performed at our institution between January 2021 and May 2022 were retrieved from our database. Eighty percent of conventional malignant melanomas were labeled diffusely positive with PRAME; there were no significant differences in mean age, sex, site, Breslow depth, ulceration status, or American Joint Committee on Cancer pathological tumor stage when comparing diffusely PRAME-positive malignant melanomas with those that lack diffuse labeling. Although no banal melanocytic nevi were labeled with PRAME, 13% of dysplastic nevi were diffusely PRAME positive, with junctional proliferations, severe atypia, male gender, and older age being associated with PRAME positivity. As some but not all ambiguous melanocytic lesions in which malignancy could not be excluded based on morphology alone were diffusely PRAME positive, PRAME's accuracy in predicting malignancy remains unclear to the authors; further study is needed to assess the precision to which PRAME immunohistochemistry can separate benign borderline lesions from their malignant counterparts. Among nonmelanocytic lesions, some poorly differentiated tumors, including atypical fibroxanthomas, can be PRAME positive. This series underscores the importance of clinicopathologic correlation and shows that diffuse PRAME positivity is highest in conventional malignant melanomas (∼80%, or 8 of 10 lesions), is seen in about half of challenging borderline lesions at our institution, and can be observed in lesions diagnosed as dysplastic nevi by our group (∼10% or 1 in 10 lesions), as well as in rare poorly differentiated malignancies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Squamous carcinogenesis is incompletely understood, but more recent genetic studies support that the order of acquired mutations is important. This paper will review more recent genetic studies with an emphasis on the potential truncal mutations, mutations critical to the trunk of the cancer evolutionary tree, in actinic keratosis, squamous cell carcinoma in situ, cutaneous squamous cell carcinoma, keratoacanthoma, and keratoacanthoma-like squamous proliferation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest None disclosed.

Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm with cutaneous involvement in ∼1% of cases. We present a single institutional series of nine patients (12 specimens) with cutaneous involvement by systemic MCL and review the clinicopathologic features. Six males and 3 females (age range 55-87 years) were included. Sites of involvement were head and neck (n = 3), trunk (n = 5), and extremities (n = 4). Histopathologically, 3 showed classic cytomorphology, 2 were blastoid, 3 pleomorphic, and 1 showed features resembling marginal zone lymphoma. Two cases presented with cutaneous lesions as the first tissue manifestation of the disease. A second malignancy was identified in 3/9 cases (2 melanomas and 1 papillary thyroid carcinoma). In one patient, MCL was juxtaposed with metastatic melanoma within the same biopsy specimen. Fluorescence in situ hybridization studies, when available, demonstrated the characteristic t(11,14) translocation. Direct immunofluorescence was performed on one case and showed immunoglobulin M (IgM) expression on the tumor cells. Follow-up was available in 7 cases (mean 42 months, range 6-78 months) and revealed death from disease for 6 patients that occurred within 1 week to 11 months (mean 4 months) after cutaneous involvement. In our series, 6/9 cases demonstrated blastoid, pleomorphic, or marginal zone lymphoma-like morphologies that could potentially mimic other hematolymphoid neoplasms. MCL may show surface IgM expression on DIF or may occur in association with other solid tumors. Immunohistochemistry for cyclin D1 and/or SOX-11 may be helpful for diagnosis, and imaging studies may be necessary to detect systemic involvement when cutaneous involvement is the first manifestation of the disease.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subset of extranodal non-Hodgkin lymphoma characterized by neoplastic lymphocytes within the lumina of small to medium-sized blood vessels. IVLBCLs are B-cell tumors that can present in essentially any organ system, including the skin. Cutaneous manifestations vary greatly and can mimic other skin disease which may delay diagnosis; in the absence of skin lesions, blind skin biopsies can be utilized for diagnosis. Early studies suggested that IVLBCL is a very aggressive lymphoma with high overall mortality rate and short survival times. However, earlier diagnosis and use of new treatment modalities have shown promise in recent studies. This case series illustrates the heterogeneity of clinical and pathologic presentations of this uncommon lymphoma., (Copyright ©2020, Yale Journal of Biology and Medicine.)

Background: Hypergranulotic dyscornification (HD) is a rarely reported histological reaction pattern that may be observed in solitary benign keratoses., Objective and Methods: We retrospectively reviewed all cases described as displaying "hypergranulotic dyscornification" at our institution between January 1st 1990 to September 1st 2018. We excluded cases that on retrospective review displayed changes of epidermolytic hyperkeratosis. We conducted electron microscopy (EM) of two lesions., Results: Thirty cases were identified in our search. Eleven patients were men and 19 were women. Their mean age was 56.9 ± 21.2 years. In contrast to previous reports, we found that HD does not spare the head and neck area. Frequent clinical impressions were inflamed seborrheic keratosis, Bowen disease or inflamed verruca. The most distinctive histopathologic finding was the presence of a prominent granular layer with clumped perinuclear keratohyaline granules. Some cases had mounds of rounded, anucleate glassy eosinophilic corneocytes in the stratum corneum. We observed one case of incidental HD occurring in an epidermoid cyst. EM of HD showed dense perinuclear bands which appeared to match areas of positive staining by keratin immunohistochemistry, without evidence of pale cytoplasmic areas devoid of keratin filaments, characteristic of epidermolytic hyperkeratosis., Conclusion: HD is a reproducible finding in some benign keratoses, probably because of abnormal keratinization. Awareness of this unique reaction pattern will help prevent misdiagnosis., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Ultraviolet radiation (UVR) exposure and family history are major associated risk factors for the development of non-melanoma skin cancer (NMSC). The objective of this study was to develop and validate a multi-parameterized artificial neural network based on available personal health information for early detection of NMSC with high sensitivity and specificity, even in the absence of known UVR exposure and family history. The 1997-2015 NHIS adult survey data used to train and validate our neural network (NN) comprised of 2,056 NMSC and 460,574 non-cancer cases. We extracted 13 parameters for our NN: gender, age, BMI, diabetic status, smoking status, emphysema, asthma, race, Hispanic ethnicity, hypertension, heart diseases, vigorous exercise habits, and history of stroke. This study yielded an area under the ROC curve of 0.81 and 0.81 for training and validation, respectively. Our results (training sensitivity 88.5% and specificity 62.2%, validation sensitivity 86.2% and specificity 62.7%) were comparable to a previous study of basal and squamous cell carcinoma prediction that also included UVR exposure and family history information. These results indicate that our NN is robust enough to make predictions, suggesting that we have identified novel associations and potential predictive parameters of NMSC.

Importance: Solid organ transplant recipients (SOTRs) have a 100-fold increased risk of squamous cell carcinoma (SCC), and they may develop more aggressive SCCs compared with immunocompetent individuals., Objective: To compare outcomes associated with aggressive behavior of SCC in SOTRs and high-risk immunocompetent patients., Design, Setting, and Participants: A retrospective cohort study of 58 SOTRs and 40 immunocompetent patients evaluated at the Yale Transplant Dermatology Clinic in New Haven, Connecticut, who had at least 1 SCC confirmed histopathologically between January 1, 2008, and December 31, 2015. Cumulative follow-up time for this study was 369 patient-years., Exposure: Immunosuppressive medication regimen for SOTRs., Main Outcomes and Measures: The primary outcome measure was tumor depth of SCC. Secondary outcome measures that reflected tumor aggressiveness included perineural invasion, regional metastases, nodal metastases, disease-specific death, and overall death., Results: Of the 58 SOTR study participants, 14 were women and 44 were men; the mean (SD) age was 61.3 (8.4) years. Of the 40 immunocompetent study participants, 16 were women and 24 were men; the mean (SD) age was 69.8 (10.9) years, resulting in a statistically significant difference from the SOTR group. The mean (SD) number of years that SOTRs were immunosuppressed was 14.6 (9.2) years (range, 2-37 years). The SOTR and immunocompetent groups were statistically comparable regarding race and sex, patient care, follow-up time, numbers of skin lesions, and field cancerization and chemopreventive therapies. The SOTR group had a significantly higher annual frequency of visits (mean [SD], 4 [2] vs 3 [2] office visits per patient per year, P = .02) and annual biopsy rates (mean [SD], 6 [4] vs 5 [3] biopsies per patient per year, P = .04). The SOTRs developed SCCs that did not appear to be significantly more aggressive than those found in the immunocompetent control group. These SOTRs also did not develop significantly thicker tumors than the immunocompetent control group (median [IQR] tumor depth, 1.30 [0.90-1.60] mm in 35 SOTRs vs 1.22 [1.10-1.60] mm in 20 immunocompetent patients)., Conclusions and Relevance: The increased risk and the potential for aggressive behavior of SCCs in SOTRs may be successfully managed at a level comparable to that in high-risk immunocompetent individuals through close adherence to current dermatologic surveillance recommendations and a marginally lower threshold for biopsy of suspicious lesions for SOTRs.

Background: Women with multiple squamous cell carcinomas (SCCs) of the legs have a striking clinical phenotype. Numerous tumors can develop in a short period of time., Objective: Because histopathologic findings can vary in women with multiple SCC lesions, from keratoacanthoma-like to well-differentiated SCC, we hypothesized that TP53 variants might shed light on the appropriate classification., Methods: We sequenced TP53 in 30 SCCs from 6 women who had multiple SCCs on their legs during a 21-month time frame., Results: Histopathologic analysis showed 16 of the 30 lesions did not have prominent cytologic atypia and were distinguished by having expanded follicle-like structures composed of large, glassy, eosinophilic keratinocytes; these lesions resembled keratoacanthoma and were categorized as keratoacanthoma-like squamous proliferations (KASPs). The 14 remaining tumors had more prominent cytologic atypia and remained classified as SCC. Twenty of 30 tumors (including the KASPs) from the 6 different patients lacked detectable TP53 mutations. Ten of the 14 tumors that remained classified as SCC had detectable TP53 mutations., Limitations: This is a small series., Conclusion: These findings suggest that some cutaneous squamous proliferations on the legs of women with multiple lesions lack prominent cytologic atypia as well as TP53 mutations and might be more akin to keratoacanthoma than SCC or might represent a reactive phenomenon., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Basal cell carcinoma (BCC) can resemble Merkel cell carcinoma (MCC) on histopathological examination and while CK20 is a useful marker in this differential, it is occasionally negative in MCC. CD56, a sensitive marker of neuroendocrine differentiation, is sometimes used to identify MCC, but has been reportedly variably positive in BCC as well. In contrast, CK5/6 consistently labels BCC but is not expressed in neuroendocrine tumors., Methods: We evaluated 20 cases of BCC for the pattern of CD56 and cytokeratin 5/6 (CK5/6) staining, hypothesizing that these 2 stains could differentiate BCC from MCC in difficult cases. Seventeen cases of MCC previously stained with CD56 were also examined., Results: All BCCs showed patchy expression of CD56 except for 2 cases, which showed staining of greater than 70% of tumor. CK5/6 was diffusely positive in all cases of BCC. Fifteen of 17 MCCs were diffusely positive for CD56. The difference in the pattern of CD56 expression between MCC and BCC (diffuse vs patchy, respectively) was statistically significant (P < .05)., Conclusion: BCC typically shows patchy CD56 expression and diffuse CK5/6 positivity. These 2 markers can be used to distinguish between BCC and MCC in challenging cases., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recent studies suggest cutaneous squamous cell carcinomas (SCCs) of the leg, particularly those occurring multiply in sun exposed skin of nonimmunosuppressed women, are a distinct clinical subtype. There are few reports of the histopathologic features of this subtype. A retrospective chart review of 4 patients with multiple SCCs on the leg was performed and a total of 35 biopsies from the legs examined. Histopathologically, the tumors lacked adjacent actinic keratosis (AK) and often had adjacent basaloid retiform proliferations. Most lesions (all but one) were well differentiated and about 40% could be classified histopathologically as keratoacanthoma. Perineural invasion was absent in all but one case. Using the American Joint Committee on Cancer (AJCC) staging criteria for SCC, 21 tumors were Stage I, and 9 Stage II. During 7-10 years of follow-up, no recurrence or metastasis occurred. Patients with multiple SCCs on the lower extremities can have a range of histopathologic features, from keratoacanthoma-like to well-differentiated SCC., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 6-month-old girl presented with an irregular nodule on the right lateral neck. The lesion, which superficially resembled a lymphangioma or mastocytoma, had been present since birth but had recently been growing. The patient was referred for surgical resection. Microscopic findings were compatible with a recently described rare hamartoma termed "panfollicular nevus," which is a well-circumscribed lesion containing aberrantly differentiated, clustered hair follicles in high density., (© 2016 Wiley Periodicals, Inc.)

Importance: Inhibition of angiogenesis is an effective anticancer strategy because neoplasms require a rich blood supply. Ramucirumab, approved by the US Food and Drug Administration in 2014 to treat gastric adenocarcinomas and non-small cell lung carcinomas, targets vascular endothelial growth factor 2 (VEGFR2). We identified a patient prescribed a regimen of irinotecan hydrochloride, cetuximab, and ramucirumab for metastatic rectal cancer (diagnosed in November 2013 and treated through early January 2015) who developed a new-onset, expanding vascular lesion on his right leg. Via exome sequencing, we found that the lesion contained a single somatic mutation in KDR (encodes VEGFR2), possibly in response to ramucirumab. Vascular tumors are not a known complication of antiangiogenic therapeutics., Observations: Exome sequencing of the well-demarcated, blanching vascular lesion on the lateral right shin revealed a somatic p.T771R mutation in KDR, without evidence of other somatic mutations or loss of heterozygosity. Histological features included lobules of small vessels within the dermis, resembling a tufted angioma., Conclusions and Relevance: A potential adverse effect of ramucirumab in combination therapy is the development of sporadic angiomas. The p.T771R mutation was previously implicated in autophosphorylation of VEGFR2 and reported in angiosarcomas alongside other driver mutations. Our observations suggest that this mutation confers a proliferative advantage in the setting of ramucirumab therapy. Patients receiving ramucirumab should be monitored for the development of new vascular lesions.

A fundamental goal in cancer biology is to identify the cells and signalling pathways that are keys to induce tumour regression. Here we use a spontaneously self-regressing tumour, cutaneous keratoacanthoma (KAs), to identify physiological mechanisms that drive tumour regression. By using a mouse model system that recapitulates the behaviour of human KAs, we show that self-regressing tumours shift their balance to a differentiation programme during regression. Furthermore, we demonstrate that developmental programs utilized for skin hair follicle regeneration, such as Wnt, are hijacked to sustain tumour growth and that the retinoic acid (RA) signalling pathway promotes tumour regression by inhibiting Wnt signalling. Finally, we find that RA signalling can induce regression of malignant tumours that do not normally spontaneously regress, such as squamous cell carcinomas. These findings provide new insights into the physiological mechanisms of tumour regression and suggest therapeutic strategies to induce tumour regression.

Background: Some patients develop a disproportionate number of cutaneous squamous cell carcinomas (SCCs) on their lower extremity (LE)., Objective: We sought to characterize the clinical features, treatment, and outcome in patients who develop multiple LE SCCs., Methods: We identified 22 patients with 4 or more biopsy-diagnosed LE SCCs during a 4.5-year study period. The location, size, treatment, and clinical outcome of each LE SCC were recorded., Results: Of the 22 patients studied, 18 were female. Of the 360 SCCs our patients developed, 260 (72.2%) were on the LE. The incidence of SCCs in these patients was nearly 7 times greater than the incidence of basal cell carcinoma in the same patients., Limitations: The number of patients is small and limits definitive conclusions about prevalence of SCCs on the LE in the general population., Conclusions: LE SCCs are a distinct subset of cutaneous SCCs and may have distinctive clinical features and biologic behavior requiring additional study., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Mutation in the folliculin gene in Birt-Hogg-Dubé (BHD) syndrome leads to a spectrum of benign tumors of the hair follicle, classically including both fibrofolliculoma and trichodiscoma. In addition, lesions clinically indistinguishable from fibrofolliculoma/ trichodiscoma may show histopathologic findings of perifollicular fibroma or angiofibroma. Although some consider perifollicular fibroma to be a variant of angiofibroma, the specific histopathologic findings of perifollicular fibroma are uncommon., Methods: This is a case series., Results: In 4 patients with multiple facial lesions, recognizing perifollicular fibroma would have been helpful in leading to the diagnosis of BHD syndrome., Conclusion: Perifollicular fibroma is on a spectrum with fibrofolliculoma and trichodiscoma; in a patient with multiple lesions, the diagnosis of perifollicular fibroma is suggestive of BHD syndrome., (Copyright © 2012 John Wiley & Sons A/S.)

Tufted angioma (TA), an uncommon benign vascular tumor, has a variable clinical presentation, and histopathologic findings are a key component of diagnosis. The presence of lymphatic vessels suggestive of lymphangioma can occasionally be the predominant finding and cause diagnostic confusion. Nine biopsies from 7 cases of TA were studied to assess the frequency and distribution of lymphangioma-like areas. Specimens were also stained with D2-40, VEGF-A, GLUT-1, and HHV-8. In one biopsy, lymphangioma-like vessels were the main finding. In all other cases of TA, lymphatics were present in the stroma but were often overshadowed by tufts of capillaries. D2-40 highlighted the stromal lymphatics and partially stained the capillaries within tufts. VEGF-A showed diffuse nonspecific staining of epidermis and endothelial cells in all specimens. GLUT1 and HHV-8 staining were uniformly negative in all 9 specimens. Accurate diagnosis of TA has important clinical implications given its occasional association with Kasabach-Merritt phenomenon, and the presence of lymphangioma-like vessels in biopsies of vascular lesions is entirely compatible with TA.

CD123-positive plasmacytoid dendrocytes are prominent in the infiltrate of discoid lupus erythematosus (LE). We hypothesized that these cells would also be present in hypertrophic LE and would aid in the histopathologic distinction from squamous cell carcinoma (SCC) and hypertrophic actinic keratosis (AK). Five cases of hypertrophic LE and 10 cases each of SCC and hypertrophic AK were stained with CD123. A heavy band of CD123-positive cells was present at the epidermal-dermal junction in all cases of hypertrophic LE, and only single or rare scattered clusters of CD123-positive cells were seen in SCC and actinic keratoses. The pattern of CD123 staining can be a useful feature to distinguish hypertrophic LE from SCC and hypertrophic AK., (Copyright © 2011 John Wiley & Sons A/S.)

Background: Melanocytic nevi may exhibit histologic features in common with cutaneous melanoma, creating diagnostic difficulties., Objective: We sought to assess the clinical behavior of melanocytic nevi with pseudomelanomatous features in association with dermal fibrosis., Methods: Forty-two melanocytic nevi with pronounced fibrosis and associated pseudomelanomatous changes were collected and studied clinically and histologically., Results: The fibrosis was centrally located and laminated in appearance. It imparted a trizonal appearance: a junctional component with prominent single cells and/or irregular nests, underlying fibrosis, and a mature dermal component. No recurrence or metastases were evident over an average follow-up period of 2 years., Limitations: The follow-up period was short., Conclusions: The central location and laminated appearance of the fibrosis suggest that this may represent the extreme end of a spectrum of fibroplastic changes in "Clark/dysplastic" nevi. Adjacent features of "Clark/dysplastic" nevi and limitation of pseudomelanomatous features to the perifibrotic focus are important in accurately identifying these lesions. Although melanocytic nevi with exaggerated fibroplasia may show foci with melanoma-like features, they do not appear to exhibit aggressive clinical behavior., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

The keratoacanthoma and its variants are clinically and histologically heterogenous. Some consider the keratoacanthoma to be benign, whereas others classify it as a subtype of squamous cell carcinoma. The keratoacanthoma is generally treated rather than observed for spontaneous resolution. This hampers evaluation of the true natural history of lesions diagnosed as keratoacanthoma. In addition, studies have not found a reliable marker to differentiate keratoacanthoma from squamous cell carcinoma. It currently remains unclear how the keratoacanthoma relates to squamous cell carcinoma, and continued investigation is necessary., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Nevi with cytologic characteristics of Spitz nevus and architectural features of Clark's/dysplastic nevus are not well recognized in the literature., Methods: Twenty-seven nevi with characteristics of Spitz nevus and Clark's/dysplastic nevus are reviewed., Results: The patients' mean age was 33 years, and 17/27(63%) patients were female. Lesions were most frequent on the trunk and lower extremities. Histopathologically, these nevi were composed of large, monomorphous spindled and/or epithelioid melanocytes. Spindle cells were often oriented parallel to the epidermis, with fused rete and lamellar fibroplasias. Lateral extension of the junctional component was a feature of compound lesions. An average of 10 years of clinical follow up in 12 patients revealed no recurrence or metastasis., Conclusions: Recognition of this type of nevus is important to avoid confusion with malignant melanoma., (2009 John Wiley & Sons A/S.)

Adenosquamous carcinoma, a rare tumor of the skin with few reported cases in the literature, has not been studied with p63, cytokeratin 5/6 and cytokeratin 7. We stained nine such tumors with these markers. Histologically, the tumors showed superficial, atypical islands of keratinocytes in close association with islands displaying glandular differentiation. Clinically, lesions favored the head and trunk, and a subset of cases showed aggressive behavior. All tumors marked with p63 and cytokeratin 5/6, substantiating that diffuse positivity with these stains is supportive of a primary cutaneous origin. Six tumors stained focally in luminal areas with cytokeratin 7. Recognition of adenosquamous carcinoma is important for appropriate therapy, and stains for p63 and cytokeratin 5/6 may be helpful in ruling out metastatic adenocarcinoma.

Numerous variants of squamous cell carcinoma (SCC) have been described. We recently encountered four examples of SCC composed primarily of single, atypical cells that were cytokeratin (CK) MNF116-positive and p63-positive. One case was particularly difficult to diagnose as the single cells were obscured by a dense inflammatory infiltrate. We have also noted similar single cell infiltration toward the periphery of four additional cases of more typical SCC. These foci resemble the single tumor cells that may infiltrate at the borders of spindle cell and desmoplastic SCCs. CK MNF116 and p63 were useful in identifying each of these neoplasms. This single--cell pattern of SCC can easily be misdiagnosed, and CK MNF116 and/or p63 are diagnostically helpful in recognizing it.

Acantholytic acanthoma was originally described as a solitary lesion displaying histologic features of acantholysis without dyskeratosis. Solitary, non-genital lesions displaying confluent acantholysis and dyskeratosis have not been well described in the literature, clinically or histologically. We screened cases at our institution over a 6-month period and found 28 such lesions. Lesions were most often found on the trunk as a solitary papule, for which the clinical diagnosis was often basal cell carcinoma. There was a slight female predominance. Confluent acantholysis and dyskeratosis is a histologic pattern that may present as a solitary keratosis.

Background: In clinical and histopathological practice, it is sometimes difficult to distinguish pseudoepitheliomatous hyperplasia (PEH) from squamous cell carcinoma (SCC) of the skin. Several studies have shown a low density of Langerhans cells in SCC of the skin, and recent research on cervical SCCs has suggested that the decreased density of dendritic cells is secondary to low E-cadherin expression. SCCs of the head and neck similarly have decreased E-cadherin expression, but E-cadherin expression is preserved in PEH. We hypothesized that PEH of the skin would have an increased number of Langerhans cells compared with SCC., Methods: We studied immunohistochemical expression of CD1a on paraffin-embedded tissue in 12 cases of SCC and 11 cases of PEH of the skin., Results: The number of Langerhans cells in SCCs vs. PEH was similar; in both types of lesions, the Langerhans cells were decreased in density compared with the normal flanking epidermis., Conclusions: PEH has a decreased number of Langerhans cells compared with the normal epidermis. As SCCs also have decreased numbers of CD1a-positive cells, this stain is not useful in differentiating these two entities.

Foci of histological changes of epidermodysplasia verruciformis (EV) were noted in five benign skin lesions. These skin lesions included an intradermal nevus, a pigmented seborrheic keratosis, an isolated papule on the forearm, a perianal lesion, and an acantholytic acanthoma. Because the changes resembled true EV so strongly despite the absence of clinical EV in these patients, we searched for EV-human papilloma virus (HPV) types in these skin lesions. Polymerase chain reaction (PCR) analysis on the formalin-fixed, paraffin-embedded blocks was performed. As a positive control, we included tissue from two HIV-positive patients with clinical EV proven by biopsy. Studies were also performed on five other archived biopsies that did not show changes of EV on multiple tissue sections. A nested PCR method detected EV-HPV types in three of the five benign skin lesions showing EV changes as well as in the positive controls. EV changes and EV-HPV can be found incidentally on biopsy in the absence of clinical EV; when such changes are the major histopathological finding in an isolated skin lesion, the lesion should be termed an EV acanthoma.

Aim: In our previous research, bcl-2-positive dendritic cells were seen in increased numbers in suprabasal areas of inverted follicular keratoses (IFKs) compared to seborrheic keratoses (SKs). The purpose of this study was twofold; firstly, to support that these dendritic cells are Langerhans cells and secondly, to contrast the epidermal dendritic cells in IFKs, squamous cell carcinomas (SCCs), and SKs., Methods: Ten IFKs and five SKs previously showing bcl-2-positive dendritic cells within the epidermis were stained with CD1a. Fifteen other IFKs were stained with CD1a alone. Ten SCCs were stained with bcl-2 and CD1a., Results: In the 10 IFKs stained with both bcl-2 and CD1a, the density of CD1a-positive cells correlated well with the density of bcl-2-positive dendritic cells; in the five SKs, the density of CD1a-positive cells was similar to that seen in IFKs but was higher compared to the density of bcl-2-positive dendritic cells in SKs (p < 0.05). The IFKs had a significantly higher number of CD1a-positive cells compared to SCCs (p < 0.01). SCCs showed bcl-2-positive cells only within the basal layer of the normal epidermis flanking the carcinomas., Conclusions: These results suggest that there is different bcl-2 regulation of CD1a-positive cells in IFKs, SKs, and SCCs.

The WHO-EORTC classification of cutaneous lymphomas is a good start to unifying nomenclature, a necessity before coherent consensus diagnoses can be made. There are three provisional diagnoses in this new classification that are not covered in detail in this review because they are rare diseases that still require further study for definitive classification. Much remains to be elucidated about cutaneous lymphomas, but understanding of the major entities within the new classification is an important first step in understanding these diverse diseases.

Onychomatricoma is a rare tumor that appears to originate from cells of the nail matrix. Three cases of onychomatricoma that met Perrin et al.'s1 histologic criteria of onychomatricoma are described. However, using a single term to classify all three tumors ignores the apparent microscopic differences that exist among them. To demonstrate better the spectrum of so-called onychomatricoma and properly acknowledge the noticeable disparity among our cases, a series of terms is proposed. This terminology is based on the histologic spectrum of epithelial-stromal ratio of stromal cellularity and of extent nuclear pleomorphism. Use of such criteria has a precedent in the classification of follicular and odontogenic fibroepithelial neoplasms. This new nomenclature includes "unguioblastoma" for tumors with a predominant epithelial component and "unguioblastic fibroma" for tumors where a cellular stroma is more prominent and characteristic. The term "atypical unguioblastic fibroma" is used to describe a third rare neoplasm, in which the cellular stroma shows nuclear pleomorphism and atypia with an increase of mitotic activity.

Juvenile hyaline fibromatosis is a rare autosomal recessive genodermatosis that manifests with 1 to 5 cm skin tumors, gingival hyperplasia, osteolytic bone lesions, and joint contractures. The skin tumors are most often located on the head and periarticular extremities. A case of juvenile hyaline fibromatosis with typical skin tumors that on biopsy exhibited basophilic calcospherules is presented. Although noted in a single case, these structures may be a novel, yet helpful, diagnostic marker.