Diagnostically Challenging Multifocal Penile Epithelioid Hemangioma Successfully Treated With Doxorubicin Hydrochloride.

ABSTRACT: Epithelioid hemangioma (EH), also known as angiolymphoid hyperplasia with eosinophilia, is an unusual vascular proliferation that tends to manifest in the head and neck region. Its occurrence on the penis is rare, with only scarce reported cases in the literature. The histopathological examination of this condition poses a challenge because it shares similarities with other entities, such as epithelioid hemangioendothelioma, epithelioid angiosarcoma, cutaneous epithelioid angiomatous nodule, or Kaposi sarcoma (KS). The infrequency of EH in penile locations underscores the need for accurate diagnostic differentiation and tailored treatment strategies for this atypical presentation. This case report highlights a rare instance of multifocal penile EH. The patient's lesions exhibited distinctive histopathologic features, with extensive eosinophilic infiltration, presence of necrosis, and infiltration to subcutaneous fat. The patient was treated with doxorubicin, a chemotherapy drug, with a very good response. This successful therapeutic outcome underscores the potential efficacy of doxorubicin in the management of multifocal penile EH. The comprehensive analysis of this case contributes to our understanding of the clinical presentation, histopathologic features, and treatment modalities for this rare penile tumor, providing valuable insights for future clinical considerations.

A comparative study of histopathologic features in alopecia areata and pattern hair loss.

BACKGROUND: When peribulbar infiltrates are absent, other histopathologic findings are necessary to distinguish alopecia areata (AA) from pattern hair loss (PHL). The purpose of this study is to determine which histopathologic features are most useful for differentiation. METHODS: A retrospective slide review was conducted of AA and PHL scalp biopsy specimens from 2014 to 2019 at a tertiary referral center. RESULTS: Ninety-six cases were retrieved, of which 38 were AA. Peribulbar infiltrates were identified in 24 AA (63.2%) cases. A catagen/telogen shift was observed more frequently in AA than PHL (25 cases, 65.5% vs. 10 cases, 17.2%; p ≤ 0.0001). Lymphocytes (4 cases, 10.5% vs. 1 case, 1.7%; p = 0.058) and melanin (25 cases, 65.8% vs. 5 cases, 8.6%; p ≤ 0.0001) in fibrous tracts were more common in AA. Apoptotic bodies within vellus hairs were more frequently identified in AA (32 cases, 84.2% vs. 37 cases, 63.8%; p = 0.030). Small dystrophic follicles were also more common in AA (16 cases, 42.1% vs. 1 case, 1.7%; p < 0.0001). CONCLUSIONS: Common features of AA other than peribulbar infiltrates include a catagen/telogen shift, melanin in fibrous tracts, and small dystrophic follicles. Practitioners should consider these features when distinguishing AA from PHL in specimens without peribulbar infiltrates. The retrospective design limits our ability to exclude multifactorial alopecia, such as telogen effluvium.

Updates in cutaneous manifestations of systemic vasculitis.

PURPOSE OF REVIEW: The main purpose of this review is to present newly reported cutaneous manifestations of systemic vasculitis, updates in investigations to verify systemic involvement in cases with cutaneous vasculitis and new therapeutic guidelines. The spectrum of COVID-19-related vasculitis is also covered. RECENT FINDINGS: Only a few reports highlighted new cutaneous presentations or associations with some systemic vasculitic entities. For example, the association of inflammatory disorders with Takayasu arteritis, the importance of considering Kawasaki disease in febrile children with erythema nodosum, the development of necrotic ulcers on fingers and toes in Behçet's disease and the possible presence of polyarteritis nodosa-like pathological features in vulvar ulcers of Behçet's disease. New attempts to classify cutaneous manifestations of giant cell arteritis (GCA) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the diagnostic investigations for cutaneous vasculitis cases to verify systemic involvement are discussed. Treatment of systemic vasculitis with cutaneous vasculitis should be tailored according to disease status. A plethora of reports in the past 2 years focused on the broad spectrum of COVID-19 vasculitic manifestations. SUMMARY: Although newly reported cutaneous manifestations of systemic vasculitis are relatively uncommon, the plethora of reports in the past 2 years on COVID-19 vasculitis necessitates the expansion of the classification of vasculitis associated with probable cause to include severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) vasculitis.

Fractional microneedle radiofrequency versus fractional carbon dioxide laser in the treatment of postburn hypertrophic scars.

BACKGROUND AND OBJECTIVE: New and improved treatment modalities, including lasers and energy-based devices, are promising treatment options for hypertrophic scars. This study aimed to assess the efficacy and safety of fractional microneedle radiofrequency (FMR) compared with fractional carbon dioxide (CO2 ) laser in the treatment of postburn hypertrophic scars. PATIENTS AND METHODS: Twenty patients with hypertrophic scars were enrolled in the study. Two areas in each patient were randomly assigned to fractional CO2 laser or FMR. Four sessions, 6-8 weeks apart were performed. The Patient and Observer Scar Assessment Scale (POSAS) was used for clinical evaluation, H & E and orcein-stained samples were examined for histopathological assessment, and tissue transforming growth factor beta 1 (TGFß1 ) levels were measured for biochemical evaluation. RESULTS: Both fractional CO2 and FMR-treated areas showed significant improvement in all parameters 1 month after treatment. Fractional CO2-treated areas showed a higher degree of improvement compared with FMR in OSAS (p = 0.025), elastin grading (p = 0.004), and TGFß1 levels (p = 0.000). Patients reported less downtime and showed less postinflammatory hyperpigmentation with FMR compared with fractional CO2, but this did not reach statistical significance (p = 0.327, p = 0.231; respectively). CONCLUSION: Our results demonstrate the value of FMR as an effective alternative to fractional CO2 in the treatment of hypertrophic scars, with a potentially favorable safety profile.

Hypopigmented lesions in pityriasis lichenoides chronica patients: Are they only post-inflammatory hypopigmentation?

BACKGROUND/OBJECTIVES: Pityriasis lichenoides chronica (PLC) lesions are reported to subside with post-inflammatory hypopigmentation (PIH); hence, the most widely perceived nature of hypopigmented macules in PLC is PIH. However, to the best of our knowledge, no studies describing histopathological findings in these lesions are reported in literature. The aim of this study is to evaluate the hypopigmented lesions encountered in PLC patients and to shed light on their histopathological features. METHODS: A cross-sectional observational study included twenty-one patients with PLC recruited in a period of twelve months. Clinical characteristics of each patient were collected. A skin biopsy from hypopigmented lesions whenever present was taken and assessed with routine haematoxylin and eosin stain. RESULTS: Seventeen patients (81%) were less than 13 years old. Most patients (85.7%) demonstrated diffuse distribution of lesions. Hypopigmented lesions were present on the face in 12 (57.14%) patients. Histopathologically, hypopigmented lesions showed features of post-inflammatory hypopigmentation in 19% of patients, residual PLC in 52.4% and active PLC 28.6% of patients. CONCLUSION: Hypopigmented lesions in PLC were noted mainly in younger ages, histopathologically they may show features of active or residual disease, beyond post-inflammatory hypopigmentation. Consequently active treatment for patients presenting predominantly with hypopigmented lesions could be required to control the disease.

Cutaneous lymphomas and COVID-19: What is known so far?

The Coronavirus disease 2019 (COVID-19) pandemic spreads quickly all over the world. There are no sufficient data in the literature about COVID-19 infection and cutaneous lymphomas. This review sheds the light on what is known so far about COVID-19 with a cutaneous lymphoma perspective. Cutaneous T-cell lymphoma (CTCL) diagnosis does not represent a predisposing factor to viral infections and most of CTCL patients have indolent disease. However, physicians should be cautious with patients with aggressive primary cutaneous lymphomas and advanced CTCL. Different treatment strategies for cutaneous lymphomas should be taken into consideration during the COVID-19 pandemic. Thus, it is highly needed to estimate the benefit-to-risk ratio on a case-by-case basis.

Nuclear and cytoplasmic features in the diagnosis of Clark's nevi.

BACKGROUND: Interpretation of Clark's nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions. METHODS: This is a retrospective observational study conducted on 100 Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all blinded and randomized photomicrographs of both the Clark's nevi and melanomas for the presence of 14 cytologic features. Subsequently, a multivariate model was used to obtain sensitivity and specificity. RESULTS: Clark's nevi showed a significantly higher frequency of absent-or-inconspicuous nucleoli over melanoma, whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular nucleus with rounded nucleoli were found significantly higher in frequency in melanomas. CONCLUSION: Our data suggest that nuclear alterations are of value in the differentiation of atypical nevi from melanoma.

Diagnostic Criteria in Intraepithelial Pagetoid Neoplasms: A Histopathologic Study and Evaluation of Select Features in Paget Disease, Bowen Disease, and Melanoma In Situ.

BACKGROUND: Paget disease, Bowen disease, and malignant melanoma in situ are intraepidermal neoplasms, characterized by the presence of pagetoid scatter of atypical cells in the epidermis. This study reviewed the frequency of select histologic criteria to validate their usefulness in the histologic distinction between these entities. METHODS: One hundred forty-four specimens with the diagnosis of Bowen disease, 144 specimens with Paget disease (mammary and extramammary), and 144 specimens with malignant melanoma in situ were examined microscopically to define frequencies of select histologic criteria present in each disease. RESULTS: Comparison between mammary Paget and extramammary Paget disease showed no significant differences in the features studied. Crushing of basal keratinocytes, presence of atypical cells in the corneum, and presence of large cells with amphophilic cytoplasm were significantly noted in Paget disease. Transition between the atypical clear cells and surrounding keratinocytes was absent in all cases of melanoma in situ and in 87 (60.4%) cases of Paget disease, but it was significantly associated with Bowen disease (98.6%). Dyskeratotic cells were significantly associated with Bowen disease cases. CONCLUSION: Our study demonstrated a practical histologic approach to differentiate between intraepidermal pagetoid neoplasms. Careful histologic study of the proposed criteria may reduce reliance on immunohistochemical stains.

Specificity of granular IgM deposition in folliculosebaceous units and sweat gland apparatus in direct immunofluorescence (DIF) of lupus erythematosus.

BACKGROUND: Diagnosis of lupus erythematosus (LE) in direct immunofluorescence testing is based on the finding of positive immunofluorescence at the dermoepidermal junction (DEJ). OBJECTIVES: We sought to evaluate the sensitivity of IgM deposition at the DEJ and adnexal structures in the diagnosis of lupus erythematosus. METHODS: We conducted a retrospective study of 100 previously diagnosed cases of lupus erythematosus and 158 cases of other immune-mediated dermatosis. Deposition of IgG, IgM, IgA, and C3 at the DEJ, follicular units, and sweat glands were recorded. Presence or absence of adnexal structures was documented. The immunoreactant deposition was documented as linear, coarse granular, or stippled. RESULTS: The most frequently deposited immunoreactant in lupus erythematosus cases was IgM along the DEJ and stromal-epithelial junction of hair follicles and sweat glands. IgM deposition along the stromal-epithelial junction of hair follicles and sweat glands was strongly associated with a diagnosis of lupus erythematosus compared with other immune-mediated diseases collectively (P value < .001). The pattern of IgM in lupus and dermatomyositis is granular, in contrast to the linear deposition in the other disorders evaluated. LIMITATIONS: This was a retrospective study of archived material. CONCLUSION: Granular IgM deposition at the stromal-epithelial junction of cutaneous adnexal structures suggests a diagnosis of lupus erythematosus or dermatomyositis.

Nuclear and cytoplasmic features in the diagnosis of banal nevi, Spitz nevi, and melanoma.

BACKGROUND: Many authors have described cytologic features in a variety of melanocytic lesions but, to our knowledge, a statistical analysis of sensitivity, specificity, and overall accuracy of these features alone or in combination has not been performed. OBJECTIVE: We sought to determine the diagnostic value of nuclear and cytoplasmic characteristics in the diagnosis of melanocytic lesions via multivariate statistical analysis. METHODS: This is a retrospective observational study conducted on 300 melanocytic lesions. We evaluated a series of distinctive features; subsequently a multivariate model was used to determine sensitivity and specificity. RESULTS: Major features that favor a diagnosis of melanoma include: pleomorphism with enlarged nuclei, mitotic figures, notching/corrugation of the nuclear envelope, and peppered moth nucleus. Features with intermediate value include: solid hyperchromasia, vesicular nucleus with single round nucleolus, and nuclear/cytoplasmic ratio greater than 4:1. LIMITATIONS: Limitations of this study include its retrospective nature, and the reliance on the original diagnostic classification of each neoplasm. CONCLUSION: Our data suggest that some nuclear alterations have greater value in the diagnosis of benign and malignant melanocytic lesions.

Pathologic features of anogenital precancerous high-grade squamous intraepithelial lesion (squamous cell carcinoma in situ).

BACKGROUND: Precancerous high-grade squamous intraepithelial lesion (HSIL), the current consensus terminology for anogenital squamous cell carcinoma in situ (SCCIS), often presents with distinctive histopathologic findings that may be a function of anatomic site or associated human papillomavirus infection. METHODS: Fifty-six specimens of anogenital HSIL were compared with an equal number of specimens of SCCIS from non-anogenital sites in regard to the presence of parakeratosis, flag sign in the stratum corneum, compact stratum corneum, hypergranulosis, koilocytes, small blue cells, clonal populations of keratinocytes, pagetoid scatter of atypical keratinocytes, clear cell change, glassy red cytoplasm, pigmentation, nuclear/cytoplasmic(N/C) ratio >2/1, nuclear hyperchromasia, pleomorphic nuclei, mitotic figures, abnormal mitotic figures, dyskeratotic keratinocytes, involvement of skin appendages, acantholysis and amyloid deposition. RESULTS: Hypergranulosis, koilocytes, small blue cells, pigmentation, nuclear hyperchromasia, dyskeratotic keratinocytes and amyloid deposition were more frequently noted in anogenital HSIL. Parakeratosis, clear cell change, pleomorphic nuclei, skin appendages involvement and acantholysis were strongly associated with non-anogenital location. There was no significant difference in the incidence of the remaining features. CONCLUSION: The strongest predicators of an anogenital location included hypergranulosis, koilocytes, small blue cells and nuclear hyperchromasia. Pigmentation and amyloid deposition were also strongly associated with an anogenital location.

When to suspect tinea; a histopathologic study of 103 cases of PAS-positive tinea.

BACKGROUND: The histopathologic features of tinea vary widely and its diagnosis could be easily missed if the index of suspicion is not high. We aimed in this study to detect histopathologic features that could be a clue for diagnosis METHODS: We retrospectively reviewed 103 cases of tinea, confirmed by Periodic acid-Schiff (PAS) staining. For each case, gender, biopsy site, and pre-biopsy suspicion were recorded. The presence or absence of 17 microscopic features was noted. RESULTS: Concordance between pre-biopsy and histopathologic diagnosis was noted in 57.28% of cases, suggesting that the diagnosis is often not suspected clinically. Among the histopathologic features studied, a compact stratum corneum (either uniform or forming a layer beneath a basket weave stratum corneum), parakeratosis, mild spongiosis and neutrophils in the stratum corneum and within the blood vessels were the most frequent features noted. CONCLUSION: This study suggests histopathologic clues that should prompt the pathologist to order a PAS stain, especially when diagnosis is not suspected clinically.

Polarized Microscopy in Lesions With Altered Dermal Collagen.

Alterations in dermal collagen are noted in dermatofibroma, dermatofibrosarcoma protuberans, morphea, lichen sclerosus et atrophicus, hypertrophic scars, and keloids. The authors sought to determine whether variations in birefringence of collagen by polarized microscopy could be of help in diagnosing such conditions. Representative hematoxylin and eosin sections of 400 cases, including dermatofibroma, dermatofibrosarcoma protuberans, hypertrophic scars, keloid, morphea, and lichen sclerosus, were examined under polarized microscopy. Distinct patterns of birefringence of collagen for each disease were noted under polarized microscopy. This study highlights the use of polarized microscopy as adjunctive tool in differentiating different diseases with collagen alteration.

Linear Sclerodermoid Lupus Erythematosus Profundus in a Child.

Lupus erythematosus panniculitis, also known as lupus profundus, is a variant in the clinicopathological spectrum of lupus erythematosus (LE) affecting about 2%-3% of LE patients. A linear configuration of LE panniculitis has been reported rarely with rare reports describing the coexistence of different forms of cutaneous LE and localized morphea. In this study, the authors present a 9-year-old girl with linear arrangement of subcutaneous nodules on her left forearm. Microscopic findings from 2 biopsies included lymphocytes at the dermoepidermal junction with mild interface dermatitis, a dense lymphocytic infiltrate that was concentrated around adnexae and subcutaneous fat in concert with thickened collagen bundles and mild widening of fibrous septae surrounding fat lobules. Although the clinical differential diagnosis included panniculitis or a sporotrichoid infection, 1 biopsy showed a dense lymphocytic infiltrate histologically bordered on that of cutaneous lymphoid hyperplasia or a late stage of Lyme disease, and a second also demonstrated more prominent sclerodermoid collagen bundles rendering the diagnosis of linear sclerodermoid LE profundus.

Hidradenoma Papilliferum With Oncocytic Metaplasia: A Histopathological and Immunohistochemical Study.

Hidradenoma papilliferum is a benign cutaneous adnexal neoplasm, commonly occurring in the vulva and perianal region of adult women. It has characteristic histopathological features composed of anastomosing and branching tubules, lined by columnar cells, and a basal layer of myoepithelial cells. A 39-year-old woman was evaluated for 2 asymptomatic labial masses. The histopathological examination revealed a Bartholin's cyst and a hidradenoma papilliferum. The latter contains a distinct area of oncocytic/oxyphilic metaplasia. Immunohistochemical stains revealed positive staining for gross cystic disease fluid protein (GCDFP)-15 and androgen receptor. GATA-3, a protein expressed in sweat glands, highlights a similar positive staining pattern with weaker staining in areas of oncocytic metaplasia. P63 highlighted the myoepithelial differentiation. In situ hybridization for Human Papilloma Virus 6, 11, 16, and 18 was negative. P53 was negative and Ki-67 was low, confirming its benign nature. Oncocytes are enlarged epithelial cells with voluminous eosinophilic granular cytoplasm resulting from staining of nonribosomal cytoplasmic components. Few reports documented it in hidradenoma papilliferum. Our case demonstrated a florid distinct appearance of this metaplasia. The immunoprofiles of this oncocytic metaplasia such as p53 negativity and positivity for androgen receptor and GCDFP-15 demonstrates similarity to apocrine metaplasia in the breast. The authors' case demonstrates the benign nature of oncocytic metaplasia and supports the common origin of oncocytic cells and columnar cells in hidradenoma papilliferum.

Durability of direct immunofluorescence (DIF) slides stored at room temperature.

BACKGROUND: Prior studies suggested that direct immunofluorescence (DIF) slides can be stored at room temperature. OBJECTIVES: We sought to determine the durability of DIF slides stored at room temperature for 5 years. METHODS: This was a retrospective study of 83 DIF slides archived at room temperature during 2010. The pattern of immunoreactants was compared with those noted in the original report. RESULTS: Loss of reactivity was limited to cases with weak fluorescence at original diagnosis. Loss of IgG was noted in 12.5% of cases, IgA in 12%, C3 in 10%, and IgM in 9.75%. Fibrin showed no loss of reactivity. Preservation of immunofluorescence was not related to site of deposition. Overall, a reliable diagnosis could be made in 75 of 79 archived cases (94.9%). LIMITATIONS: Cases had been archived for periods varying from 4.5 to 5 years. Variations in processing and fluorochromes could affect durability. We have no way of knowing how long slides had been exposed to ultraviolet light at the time of initial examination. CONCLUSION: DIF showed excellent durability in slides kept at room temperature for 5 years.