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Histoplasmosis is a dimorphic fungal infection, which is rare outside endemic pockets in North, Central, and South America, Asia, and Africa. Herein, we describe a woman in her 80s living in the Scottish Borders region of the United Kingdom with a recent diagnosis of granulomatous rosacea, who on receiving escalating immunosuppression for suspected sarcoidosis, and long-standing rheumatoid arthritis developed a striking eruption involving her eyelids along with painful ulceration of the oral and nasal mucosa. Histopathologic examination of the skin and mucosal lesions demonstrated granulomatous inflammation with numerous yeast forms of fungal organisms with morphological characteristics of Histoplasma species. This was confirmed to be H. capsulatum on fungal culture and direct panfungal polymerase chain reaction assay. Although the patient had not left the United Kingdom for more than 20 years, she gave a travel history involving multiple trips to countries where histoplasmosis is known to occur, before that. This case exemplifies the challenges involved in making a diagnosis of histoplasmosis in nonendemic regions for both clinicians and pathologists alike. In this particular patient, the diagnostic difficulties were compounded by the clinicopathological overlap with other cutaneous and systemic granulomatous disorders like granulomatous rosacea and suspected sarcoidosis and also the exceptionally long latency period between the purported historical primary infection and recent recrudescence. We highlight this unusual case to increase an awareness of histoplasmosis, which is very rare in nonendemic regions like the United Kingdom and involves cases acquired during residence in or travel to endemic areas, to ensure its prompt recognition and treatment.

We present a case of trichoblastic carcinosarcoma with panfollicular differentiation. An 80‐year‐old man presented with a lesion on the left ear, which had been present for several months. Histopathology revealed a well‐demarcated neoplasm in the dermis composed of intimately intermingled malignant epithelial and mesenchymal cells. The epithelial component showed multilineage follicular differentiation toward all of the elements of a normal hair follicle. Molecular analysis revealed identical molecular aberrations in both epithelial and mesenchymal components including CTNNB1 and SUFU mutations. To the best of our knowledge, this is the first report of panfollicular carcinosarcoma and of the presence of a CTNNB1 mutation in trichoblastic carcinosarcoma.

Immunofluorescence is an essential technique for the accurate diagnosis and classification of immune-mediated inflammatory dermatoses. We report a case of lichen planus pemphigoides, a very rare entity within this group of dermatoses, which shows overlapping features of lichen planus and bullous pemphigoid. We discuss the value of pattern-based morphologic assessment and clinical correlation, along with the vital role of immunofluorescence in arriving at the correct diagnosis.

Despite the efficacy of BRAF-targeted and PD-L1-related immune therapies in tackling metastatic melanoma, a significant number of patients exhibit resistance. Given this, the objective of the current study was to ascertain concordance of somatic mutations in BRAF/NRAS/TERT and immunohistochemical PD-L1 and CD8 in matched primary cutaneous and metastatic melanoma. A total of 43 archival paired samples with sufficient material for genetic and immunohistochemical analyses met the criteria for inclusion in the study. Immunohistochemistry was performed for PD-L1 and CD8 and direct-DNA Sanger sequencing for BRAF/NRAS/TERT promoter mutational analyses. Agreement between paired samples was assessed using Cohen κ. Poor concordance among primary and corresponding metastases was noted in BRAF (9/42 cases discordant, κ = 0.49; 95% confidence interval [CI], 0.21-0.77; P = .0013), TERT promoter mutations (13/41 cases discordant, κ = 0.33; 95% CI, 0.04-0.62; P = .033), tumoral PD-L1 immunoexpression (9/43 cases discordant, κ = 0.39; 95% CI, 0.07-0.72; P = .0099), and immunoexpression of CD8+ T lymphocytes (12/43 cases discordant, κ = 0.44; 95% CI, 0.19-0.69; P = .002). Although NRAS1 and NRAS2 were highly concordant (42/43 and 39/43 cases, respectively), discordant NRAS2 mutational status was associated with a median time to metastasis of 90 versus 455 days for pairs with concordant status (P = .07). Although limited by sample size, our findings suggest that consideration be given to mutational analysis of metastatic tissue rather than the primary to guide BRAF-targeted therapy and question the roles of TERT promoter mutations and PD-L1 as predictive biomarkers in malignant melanoma.

The specific histopathologic diagnosis of a primary acantholytic disorder takes into account the distribution and extent of acantholysis, presence or absence of dyskeratosis, nature of the dermal inflammatory cell infiltrate, and immunofluorescence findings. Herpes virus infection is a common cause of secondary acantholysis where distinctive viral cytopathic changes aid in making it a clear-cut diagnosis in majority of cases. We present a case of coexistence of Hailey-Hailey disease and herpes simplex virus infection to compare and contrast their histopathologic features. This is imperative because acantholytic cells from primary acantholytic disorders may occasionally show cytological features traditionally associated with herpes virus infection (pseudoherpetic changes). The objective of this article is to create a greater awareness of pseudoherpetic changes and also to explore the clinical significance of coexistence of a primary acantholytic disorder and herpes virus infection, as in this case.

Nicolau syndrome is a rare form of iatrogenic cutaneous necrosis which affects injection sites. Although classically associated with intramuscular injections, it may develop after subcutaneous or other routes of parenteral drug administration. Clinically, it manifests as necrotic ulcers that often develop in a background of erythematous and livedoid reticular patches. The histopathologic characteristics of Nicolau syndrome are poorly documented in the dermatopathology literature and features only rarely as one of the obscure causes of cutaneous thrombotic vasculopathy. We report a case of Nicolau syndrome developing secondary to subcutaneous injection of cyclizine to familiarize the clinicians and pathologists to this unusual condition. Given that it is potentially avoidable, pathologists should alert the clinicians to the possibility of Nicolau syndrome when a skin biopsy from an injection site shows signs of extensive thrombotic vasculopathy.

Lipodermatosclerosis (LDS) is a well-recognized form of fibrosing panniculitis. Although chronic cases are readily diagnosed, early and evolving lesions may be clinically mistaken for cellulitis and other forms of panniculitis. Most pathologists are familiar with a pseudomembranous type of fat necrosis as a useful feature of chronic LDS. Although nonspecific, this distinctive pattern of fat necrosis helps in supporting a diagnosis of LDS in the appropriate clinical context. The histopathologic features of early and evolving LDS and those involving the dermis are less well documented. We report a case of early LDS showing extensive pseudomembranous changes in the dermis on a superficial skin biopsy where progression to a classic established lesion was documented clinically. We suspect that this previously unreported and unusual finding may be a histopathologic clue for evolving lesions of LDS.

The histopathological distinction between florid pseudoepitheliomatous hyperplasia (PEH) and squamous cell carcinoma (SCC) is frequently difficult. Knowledge of the list of underlying conditions known to be associated with PEH and the recognition of features of such entities under the microscope are crucial to avoid a misdiagnosis of malignancy. The link between pyoderma gangrenosum (PG) and PEH is poorly understood and has been rarely mentioned in the literature. Given the lack of specific clinical and histopathological diagnostic features of PG, distinguishing PEH and SCC in epidermal proliferations associated with PG is particularly problematic. We report a case of PG of the dorsal hands which was initially mistaken for a well differentiated SCC on a skin biopsy and only correctly diagnosed on careful clinicopathological review.

AIMS Neurofibromas (NFs) and melanocytic nevi share a common neuroectodermal origin and may occasionally show overlapping morphological features. The objective of this study was to assess the prevalence and spectrum of melanocytic proliferation/differentiation in NFs and also to test the hypothesis whether detection of this feature could be used as a potential clue for neurofibromatosis type 1 (NF-1). METHODS This was a retrospective study of 229 syndromic and 239 sporadic cutaneous NFs. Each case was assessed for an associated melanocytic component, both within the tumor and the overlying epidermis. Melan A immunohistochemistry was used in selected cases to further characterize this feature, particularly in diffuse NFs. RESULTS An associated melanocytic component was detected in 77/229 syndromic and 12/239 sporadic cases (P < 0.00001). This was in the form of a junctional proliferation (lentiginous melanocytic hyperplasia or junctional nevus) or dermal differentiation (diffuse spindle cell or dermal nests of pigmented epithelioid melanocytes). CONCLUSIONS Our study affirms that the spectrum of melanocytic proliferation/differentiation in NFs is broad and probably under-recognized. Awareness of this phenomenon is critical to avoid misdiagnosis of some diffuse NFs as primary melanocytic tumors, for example, desmoplastic melanomas. Given the strong link between dermal melanocytic differentiation and syndromic NFs, its detection could potentially serve as a useful clue for NF-1 in an appropriate clinical context.

Background Granular cell tumors (GCTs) are uncommon mucocutaneous and soft tissue neoplasms with distinctive histopathologic appearance but controversial histogenesis. Herein, we report a variant of cutaneous GCT featuring extensive desmoplastic stroma which may result in diagnostic difficulties with mesenchymal proliferations, particularly a dermatofibroma. Methods Following a recent case of GCT with prominent stromal desmoplasia, we reviewed all cases diagnosed as GCT during the past 10 years accessioned at the dermatopathology unit in a tertiary university hospital. Results Three additional cases with a similar excessive connective tissue were identified out of a total of 49 GCTs. Cytoplasmic granularity was often subtle and focal, S100 expression was weak, and nuclei had a tendency to show spindling in tumor cells entrapped within the desmoplastic areas. Of note, nuclear spindling is one of the criteria used to diagnose an atypical/malignant GCT. Conclusion We propose the term "desmoplastic GCT" for these tumors, which not only appropriately addresses the stromal changes but also raises an awareness of GCT being one of the cutaneous tumors which may show stromal desmoplasia. Differential diagnostic difficulties apart, awareness of this phenomenon is important so that desmoplasia and resultant spindling are not linked with potential aggressive behavior.

Estimates of the frequency of telomerase reverse transcripter (TERT) mutations in desmoplastic melanoma (DM) are limited. DM is categorized into subtypes, pure and mixed, differing in prognosis, suggesting genetic heterogeneity. Given this, our aims were to determine the incidence of TERT promoter mutations in DM subtypes and to evaluate its relationship with established histopathologic prognosticators, BRAF and RETp status, and neurofibromin protein expression. Of the archival annotated samples retrieved, 76 cases of DM (48 pure and 28 mixed) fulfilled the criteria for inclusion. PCR amplification of the TERT promoter region was performed on DNA extracted from formalin-fixed paraffin-embedded tissue using primers5'-GCCGATTCGACCTCTCTCC-3' (forward) and 5'-CAGCGCTGCCTGAAACTC-3' (reverse). For each case, appropriate C>T mutations were identified on the electropherograms. Univariate analysis using χ-test was carried out to identify potential confounders; a nested case-control study of demographic, clinical, histopathological, and genetic determinants was carried out using multiple logistic regression. Significant differences in TERT promoter mutation frequencies were noted in the subtypes (mixed vs. pure; 15/28, 54% vs. 11/48, 23%, respectively, P=0.0066). After adjusting for potential confounding, multivariate analyses indicated a three-fold increase in the odds of the TERT mutation for those with the mixed subtype compared with the pure subtype (P=0.04, adjusted odds ratio =3.32). No other significant associations were noted (sex/junctional component/Breslow depth/ulceration/mitoses/host response/RETp, BRAF status, and neurofibromin protein expression). Our findings, the largest to date investigating TERT promoter mutations in DM, support the hypothesis that the subtypes have distinct genetic drivers and underscore the relevance of telomere integrity in the etiopathogenesis of the mixed variant.

Summary Loss of the NF1 allele, coding for the protein neurofibromin, and polymorphism in the proto-oncogene RET ( RETp ) are purportedly common in desmoplastic melanoma (DM). DM is categorized into pure (PDM) and mixed (MDM) subtypes, which differ in prognosis. Most NF1 mutations result in a truncated/absent protein, making immunohistochemical screening for neurofibromin an ideal surrogate for NF1 allelic loss. Using antineurofibromin, our aims were to ascertain the incidence of neurofibromin loss in DM subtypes and to evaluate the relationship with RET , perineural invasion (PNI) and established histopathologic prognosticators. A total of 78 archival samples of DM met criteria for inclusion (54 cases of non-DM serving as controls). Immunohistochemistry was performed for neurofibromin, whereas direct DNA sequencing was used for RETp and BRAF mutation status. Statistical analyses included χ 2 test as well as Fisher exact test. Neurofibromin loss was more common in DM than non-DM (69% versus 54%; P =.02). In DM, significant differences in neurofibromin loss were noted in the following: non–head and neck versus head and neck biopsy site (88% versus 55%) and PDM versus MDM variants (80% versus 56%). No significant associations were noted with sex, presence of a junctional component, Breslow depth, ulceration, mitoses, host response, RETp , BRAF status, or PNI. RETp was marginally associated with PNI-positive DM versus PNI-negative DM (36 versus 18%; P =.08). Our findings, the largest to date investigating neurofibromin in DM, validate the incidence of NF1 mutations/allelic loss in DM and suggest that the DM subtypes have distinct genetic drivers.

Basal cell carcinoma (BCC) is the commonest malignant neoplasm in humans. Although a histopathological diagnosis of BCC is straightforward in the vast majority of cases, unusual histological variants can present a diagnostic challenge. A small proportion of BCCs show features which are generally associated with cutaneous adnexal neoplasms. Such changes may involve either the epithelium or the stroma and can mislead the pathologist particularly in small biopsies. Despite the growing evidence which speculate that BCC is a primitive follicular tumor, it is unusual to encounter tumors which actually show definitive signs of adnexal differentiation. This review aims to address this somewhat overlooked aspect of a very common tumor and offers practical guidance to distinguish them from adnexal neoplasms which they might mimic.

Granulomatous pigmented purpuric dermatosis (PPD) is a rare and poorly recognized histological variant of PPD, which commonly affects the distal extremities of mainly Far East Asian patients. Many of the reported cases are associated with hyperlipidemia or other associated systemic derangements. The authors hereby describe an additional case of granulomatous PPD affecting a 56-year-old Caucasian woman presenting unusually as a solitary lesion confined to the lower back. The report also describes dermoscopic findings, summarizes clinicopathological features of all the cases published till date, and discusses the histopathological differential diagnosis.

Fibrous papule (FP) is a common benign lesion located primarily in the nose. Although its histogenesis has been marred with controversies in the past, the dermal dendrocyte is now largely accepted to be the putative cell of origin. Histopathologic diagnosis of an FP is straightforward in most cases, which shows characteristics of an angiofibroma. Several histologic variants have been described, recognition of which is important to avoid a misdiagnosis and inappropriate treatment. This review presents a historical perspective into the histogenesis, discusses the histopathologic features and potential diagnostic pitfalls of classic FP, and lists the various histologic variants and their differential diagnoses.

Porokeratosis is a family of several disorders characterized histologically by the presence of cornoid lamellae. The presence of cornoid lamellae represents an abnormal form of keratinization, which unifies all types of porokeratosis. A significant variation in lesional morphology can result from peculiarities involving the cornoid lamellae and changes related to epidermal hyperplasia and dermal inflammation. This diversity has led to the recognition of several unusual clinicopathological variants of porokeratosis in recent years. Cornoid lamellation, however, is not pathognomonic of porokeratosis and can be seen in some inflammatory and inherited cutaneous disorders and also as an incidental finding. Some of these conditions can be confused with an atypical presentation of porokeratosis and vice versa. An awareness of the broad morphological spectrum of porokeratosis is crucial to avoid missing the diagnosis when appearances are far from typical. This issue is critical in patient management given the potential premalignant nature of porokeratosis.

Although tattooing is an ancient practice, its increasing popularity and social acceptance, variability of tattoo ink composition, sporadic reports of novel tattoo reactions and advances in the field of tattoo removal techniques make it a topic of immense interest among dermatologists and pathologists alike. Since effective legislation governing the tattoo industry is largely lacking in most regions of the world, it is important to recognize the range of tattoo-related complications from a dermatopathological perspective. Using a pattern-based approach, this review details the broad spectrum of inflammatory reactions, which may be encountered in adverse reactions associated with tattooing. Awareness of the range of inflammatory tattoo reactions is crucial as some of these patterns of inflammation can be associated with systemic disorders and others may serve as important clues for an underlying infective condition.

The incidence of malignant skin tumours has significantly increased in recent years. In addition to establishing a diagnosis, histopathological assessment of these tumours provide vital prognostic information which often inform decisions related to onward referral, optimal treatment and planning of follow-up care. Using the example of the three most common skin cancers (basal cell carcinoma, squamous cell carcinoma and malignant melanoma), this review outlines how the contents of the histopathology reports influence patient management. Particular emphasis is given to highlight histologic parameters which are directly linked to a specific management issue. Unravelling the molecular pathogenesis of some of these tumours has paved the way for development of novel molecular targeted therapies in recent years. It is hoped that this article will familiarize the reader with some of these recent developments and also improve their overall understanding of the role of pathology in a multidisciplinary team setting towards management of cancer patients.

Although relatively uncommon, there exists a group of potentially life threatening inflammatory skin disorders where early diagnosis and treatment is of paramount importance. Clinically, such critical inflammatory dermatoses can fall under the categories of adverse drug reactions, infections or primary skin conditions. The latter may sometimes involve a paraneoplastic dermatosis which can either precede an occult underlying malignancy or signal possible tumour recurrence. Using the standard pattern-based approach to inflammatory skin disorders, this review offers a clinicopathological overview of select examples which are sufficiently distinctive for recognition under the microscope. The importance of clinicopathological correlation in these conditions is perhaps more crucial than anywhere else in dermatopathological practice due to the management implications of many of these diagnoses.

Background We reviewed all cases of Mycobacterium chelonae infection seen in our department between 1 January 2008 and 31 December 2012. Objectives To review the epidemiology, clinical features and management of cutaneous M. chelonae in South-East Scotland, and to compare prevalence data with the rest of Scotland. Methods The Scottish Mycobacteria Reference Laboratory database was searched for all cases of cutaneous mycobacterial infections. Results One hundred and thirty-four cases of cutaneous mycobacterial infection were recorded. Sixty-three were tuberculous; of the remaining 71, M. chelonae was the most common nontuberculous organism (27 cases). National Health Service (NHS) Lothian Health Board was the area with highest incidence in the Scotland (12 cases). Three main groups of patients in the NHS Lothian Health Board contracted M. chelonae: immunosuppressed patients (n = 6); those who had undergone tattooing (n = 4); and others (n = 2). One case is, we believe, the first report of M. chelonae cutaneous infection associated with topical corticosteroid immunosuppression. The majority of patients were treated with clarithromycin monotherapy. Conclusion The most prevalent nontuberculous cutaneous mycobacterial organism in Scotland is M. chelonae. The prevalence of M. chelonae in Edinburgh and the Lothians compared with the rest of Scotland is disproportionately high, possibly owing to increased local awareness and established facilities for mycobacterial studies. Immunosuppression with prednisolone appears to be a major risk factor. The first outbreak of tattoo-related M. chelonae infection in the U.K. has been reported. Clinicians should be aware of mycobacterial cutaneous infection and ensure that diagnostic skin samples are cultured at the optimal temperatures.

The association between morphea and perineural inflammation has been reported sporadically but never studied systematically. To assess the prevalence and nature of perineural inflammation in various clinicopathologic stages of morphea and a cohort of other inflammatory dermatoses, 80 morphea and 36 control skin biopsies were studied using hematoxylin/eosin and S100 stains. Perineural inflammation was semiquantitatively analyzed (scored), which along with the pattern (concentric vs. marginal) and cellular composition was compared in the two groups. Perineural inflammation was identified in 84% and 61% of morphea and control cases, respectively. Examination of only routinely stained sections could still detect this feature in 58% of morphea and 33% of control biopsies. Mean perineural inflammation score in morphea (0.65) was significantly higher than in the control group (0.23) (p

Background Evidence favoring a critical role for mast cells (MC) in cutaneous malignancies is conflicting. Methods Using the immunohistochemical stain tryptase, MC counts were performed in the following tumor categories: epithelial (basal cell carcinoma [BCC]: nodular [N], n = 10, infiltrative [I], n = 10; squamous cell carcinoma [SCC]: well differentiated [W], n = 9, moderate/poorly differentiated [MP], n = 15); melanocytic (intradermal nevus, n = 10, malignant melanoma in situ [MMIS], n = 8, invasive melanoma, n = 15); vascular (hemangioma [HEM], n = 11, Kaposi's sarcoma [KS], n = 14, angiosarcoma [AS] n = 8); and fibrohistiocytic (dermatofibroma [DF], n = 7, atypical fibroxanthoma [AFX], n = 5, dermatofibrosarcoma protuberans [DFSP], n = 5). MC (intra- and peritumoral) were expressed as cells per 10 high-power fields. Results Mean MC counts were: BCCN 166.30; BCCI 130; SCCW 167.22; SCCMP 133.80; nevus 156.40; MMIS 93; MM radial growth phase 73.86; MM vertical growth phase 82.13; HEM 165.18; KS 120.57; AS 168.13; DF 247.86; AFX 280.20; and DFSP 83.60. Using a one-way analysis of variance, statistically significant differences were observed in the following pairs: AFX and DF vs. DFSP, nevus vs. melanoma, AS and HEM vs. KS. Conclusions Our findings appear to point towards a dichotomous role for mast cells in fibrohistiocytic and vascular neoplasms and argue against their preferential recruitment in epithelial malignancies and malignant melanoma. The value of mast cell counts as a prognostic index appears to be limited in most cutaneous malignancies.

Recently, patients with metastatic desmoplastic melanoma (DM) have been shown to respond more favorably to anti-PD1/PD-L1 therapy than other melanoma subtypes. Given this, we evaluated PD-L1/2 expression in primary DM samples and correlated these with subtype, CD8+ lymphocyte status, histopathological prognosticators, and select genetic alterations. Eighty-six (36 mixed DM, 50 pure DM) archival annotated samples met inclusion criteria and were immunohistochemically semiquantitatively evaluated. Per established criteria, for PD-L1/L2, cases with ⩾5% tumoral expression, and for CD8, cases with a predominantly peri/intratumoral CD8+ infiltrate were scored positive. Univariate analysis (chi-square and Wilcoxon) identified potential confounders and a nested case–control study was accomplished using multiple logistic regression. For PD-L1, 49% of cases were positive and 71% of cases with thickness >4 mm were positive; PD-L1 expression differed by median depth (3.29 mm, interquartile range=3.58 mm for PD-L1 positives vs 1.75 mm, interquartile range=2.04 mm for PD-L1 negatives, P=0.0002) and was linearly associated with increasing depth of invasion (P=0.0003). PD-L1-positive cases were more likely to display CD8+ lymphocytes (60 vs 28% P=0.0047).The presence of CD8+ lymphocytes correlated significantly with depth of invasion >1 mm (P=0.022). On multivariate analysis, PD-L1 was 6.14 × more likely to be expressed in mixed DM than pure DM (P=0.0131), CD8+ staining was 6.22 × more likely in PD-L1 positive cases than in PD-L1 negative (P=0.0118), and tumor depth was associated with greater odds of PD-L1 expression (OR=1.61, P=0.0181). PD-L2 expression was observed in 48% of cases but did not correlate with any variables. Correlation of tumoral PD-L1 with increased depth and CD8+ lymphocytes implicates the tumoral immune microenvironment with advancing disease in DM. Enhanced tumoral PD-L1 expression in the mixed cytomorphological variant provides an insight into the differential pathogenesis of the subtypes and suggests that these patients are likely better candidates for anti-PD/PD-L1 therapy.

Non-tuberculous mycobacteria represent a heterogenous group of opportunistic pathogens which differ from Mycobacterium tuberculosis in their culture characteristics and sensitivities to various antimycobacterial agents. The incidence of cutaneous infection by these organisms has increased dramatically in the past several years due to widespread use of immunosuppressive therapies. Clinically, the features can be diverse with many patients having unusual presentations. The histological changes vary from a predominantly suppurative process to pure granulomatous inflammation, depending on the duration of the lesion sampled and the immunological status. Although the microscopic features are not species specific, a predominantly suppurative dermatitis with small pseudocystic spaces is often seen in cutaneous infections by a rapid growing non-tuberculous mycobacterial species. The granulomatous inflammation accompanying such cases is often, either poorly formed or absent. An awareness of this phenomenon should prompt the histopathologist to request pertinent histochemical stains and also guide the clinician towards appropriate ancillary microbiological investigations.

With the rising popularity of tattoos, adverse skin reactions to this practise are being increasingly recognized. Most tattoo reactions involve dermal inflammatory changes. Florid pseudoepitheliomatous hyperplasia is a rare and poorly recognized complication of tattooing. Lack of awareness of this association may result in a misdiagnosis of squamous cell carcinoma. Careful consideration of the clinicopathological context is of paramount importance to make this distinction. Although exceptionally rare, genuine squamous cell carcinoma and keratoacanthoma can sometimes develop in tattoo sites. Because of this, full thickness biopsies and complete excision of the hyperproliferative area should be recommended. In contrast to pseudoepitheliomatous hyperplasia, a squamous cell carcinoma generally tends to develop much later.

The skin biopsy is considered one of the most important tools in dermatology. Two primary reasons a clinician may perform a skin biopsy are either to establish a diagnosis or to evaluate therapy. The objective of this study was to critically assess the value of the skin biopsy as a diagnostic test for inflammatory dermatoses. One hundred consecutive skin biopsy specimens where an inflammatory dermatosis was queried were reviewed. To assess the diagnostic ability of the skin biopsy, the frequency with which a correct diagnosis was made based on histopathological analysis alone was recorded, that is, an initial "blind" diagnosis made without clinical data. Once this was recorded, the clinical history was provided and a posthistory diagnosis reached. The posthistory diagnosis was then compared with the final working diagnosis in the patient case notes. In 55% of cases, histology was able to provide a prehistory specific diagnosis. In 31% of cases, histology was not able to provide a specific diagnosis but could provide a differential diagnosis. In two thirds of these (20 of the 31 cases), the diagnosis was reached posthistory with clinicopathologic correlation. In 12% of cases, histology could only provide a pattern analysis, and in 2% of cases, only a descriptive report could be issued. In 13% of cases, the biopsy provided the final working diagnosis, which had not been considered clinically. The skin biopsy for inflammatory dermatoses is clearly a worthwhile investigative procedure. Prehistory blind histology based on microscopic data provided an accurate diagnosis correlating to the working diagnosis in 53% of cases. The diagnostic boundaries of dermatopathology are such that in an additional 25 cases (25%) a diagnosis was reached with aid of clinical data proving the importance of providing a well-thought-out differential diagnosis. Overall, in 78% of cases, histology with the aid of clinical information was able to provide an accurate diagnosis correlating to the working diagnosis.

Distinction between a cutaneous lymphoma and pseudolymphoma can sometimes be exceedingly difficult. An increasing number of reactive inflammatory conditions with large numbers of CD30-positive atypical cells are being recognized. Some of these cases may be potentially misdiagnosed as a cutaneous lymphoma (CD30-positive lymphoproliferative disorder) on morphology alone. Cutaneous herpesvirus infection, particularly when developing in immunosuppressed individuals, can present as a pseudolymphoma with numerous CD30-positive blastoid cells. A careful search for viral cytopathic changes in the epidermis and adnexal epithelium, along with correlation with the overall clinical picture and appropriate ancillary investigations, may be necessary to establish a correct diagnosis.

Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare cutaneous hamartoma characterized by abundant bundles of mature skeletal muscle fibers admixed with other mesenchymal elements. We report a case of RMH in a 7-month-old girl with associated lentiginous melanocytic hyperplasia. The melanocytic hyperplasia was not apparent clinically and was only evident on histological examination. Unlike a smooth muscle hamartoma, melanocytic abnormalities have never been described in the context of RMH. Though the exact significance of this observation is not clear, we speculate that the melanocytic hyperplasia could be related to an inductive phenomenon or constitute a part of the overall hamartomatous process. Careful attention to epidermal changes in future cases of RMH may help in understanding the significance of this association and refine our knowledge of the pathogenesis of RMH.

Molluscum contagiosum (MC) can rarely show follicular neogenesis as a result of proliferation of virus-infected basal cells. We report a case of molluscum contagiosum showing multifocal areas of primitive follicular induction involving the adjacent surface epidermis. The underlying dermis showed histological features suggestive of secondary anetoderma. The pathogenetic mechanisms behind development of these microscopic features and the putative link between follicular induction and secondary anetoderma are explored. Awareness of this unusual phenomenon will be helpful in avoiding a misdiagnosis of a superficial basal cell (trichoblastic) carcinoma in such cases.

Alterations in the dermal connective tissue can sometimes induce epidermal changes with adnexal differentiation. Typically associated with dermatofibromas, such changes can also be seen in a wide range of reactive and neoplastic conditions. Scar is sometimes listed as an underlying cause of follicular induction, but this association seems to be poorly recognized and not widely discussed in the literature. In this article, the authors illustrate the spectrum of follicular induction, which may be associated with a dermal scar emphasizing on patterns, which can be mistaken for a basal cell carcinoma.

Basal cell carcinoma (BCC) is the commonest malignant neoplasm in humans. Although a histopathological diagnosis of BCC is straightforward in the vast majority of cases, unusual histological variants can present a diagnostic challenge. A small proportion of BCCs show features which are generally associated with cutaneous adnexal neoplasms. Such changes may involve either the epithelium or the stroma and can mislead the pathologist particularly in small biopsies. Despite the growing evidence which speculate that BCC is a primitive follicular tumor, it is unusual to encounter tumors which actually show definitive signs of adnexal differentiation. This review aims to address this somewhat overlooked aspect of a very common tumor and offers practical guidance to distinguish them from adnexal neoplasms which they might mimic.

The association between morphea and perineural inflammation has been reported sporadically but never studied systematically. To assess the prevalence and nature of perineural inflammation in various clinicopathologic stages of morphea and a cohort of other inflammatory dermatoses, 80 morphea and 36 control skin biopsies were studied using hematoxylin/eosin and S100 stains. Perineural inflammation was semiquantitatively analyzed (scored), which along with the pattern (concentric vs. marginal) and cellular composition was compared in the two groups. Perineural inflammation was identified in 84% and 61% of morphea and control cases, respectively. Examination of only routinely stained sections could still detect this feature in 58% of morphea and 33% of control biopsies. Mean perineural inflammation score in morphea (0.65) was significantly higher than in the control group (0.23) (p 0.0001) and the inflammation tended to show a concentric pattern with plasma cell neurotropism. Intraneural inflammation was limited to four morphea cases. Although perineural inflammation is common in morphea, it is not unusual to find this feature in other inflammatory conditions. Nevertheless, perineural inflammation can serve as an important diagnostic adjunct in difficult cases of morphea if one considers its greater intensity, predominantly concentric pattern and the tendency to show plasma cell neurotropism.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade sweat gland carcinoma with a strong predilection to the eyelid region. It is histologically analogous to endocrine ductal carcinoma/solid papillary carcinoma of the breast and is characterized by a multinodular solid cystic mucinous tumor with immunoreactivity to neuroendocrine markers. Only 20 cases of this unusual tumor have been reported. We present the clinical and histopathologic findings of 2 new cases of EMPSGC and review the relevant literature. The histological differential diagnosis is discussed and attention drawn to the role of immunohistochemistry in clarifying the nosological position of EMPSGC within the spectrum of cutaneous mucinous neoplasms.