Selective Clonal Regression After Interferon Therapy in Metastatic Melanoma.

ABSTRACT: Regression (total or partial) is a common phenomenon in melanoma. From a pathogenic perspective, it is highly complex and only partially understood, involving aspects of both the tumor and the individual. One of the determining factors is the clonal selection of the tumor, wherein some clones within the tumor survive while others perish. This clonal selection can sometimes occur as a selective mechanism after the initiation of a therapeutic intervention. In many of these cases, the effect is detrimental, because the surviving clone is resistant to the applied therapy. However, occasionally, the therapy can successfully select the less harmful clone. We present an example of the latter, where therapy with interferon induced regression of the metastatic-capable melanocytic population, with only the primary tumor melanocytic population persisting. To confirm this, we demonstrated BRAF mutational similarity between the 2 populations, and an additional NRAS mutation in the metastatic population, which was absent in the primary tumor.

Cocaine-Induced Plasma Cell Orificial "Dermatomucositis": A More Accurate Descriptive Term for a Clearly Dermatological Entity.

ABSTRACT: Although the involvement of the nasal passages and nasal septum in cocaine users has been known for decades, a new presentation affecting the nostrils and upper lip with an inflamed appearance has recently been documented. The authors who identified this presentation termed it "cocaine-related plasma cell mucositis" due to the abundance of plasma cells in the infiltrate. In this article, we present a second case and emphasize the dermal involvement of the lip, leading us to consider the condition as a genuine dermatomucositis.

Two Cases of FAVA With an Uncommon Localization in Adults.

ABSTRACT: The fibroadipose vascular anomaly (FAVA) is a relatively unknown vascular anomaly in the realm of adult dermatopathology. Despite its intramuscular location, dermatologists often encounter cases, approaching them surgically under the presumption of a potential lipoma. This entity was first described in 2014, and consequently, many FAVA cases may be concealed in our archives under diagnoses of other entities that require differential diagnoses, such as intramuscular fast-flow vascular anomaly. Clinically, these anomalies typically manifest preferably in young women or girls and predominantly in the extremities. In this article, we present 2 cases of FAVA with atypical clinical features in terms of their topography and age at onset. However, histopathologically, they exhibit typical characteristics with fibroadipose tissue and dysmorphic venous vessels dissecting the affected striated muscle.

Basic Concepts in Nail Pathology.

ABSTRACT: Understanding nail pathology is complex for general pathologists and even for those dermatopathologists who do not receive many nail samples in their laboratories. In this article, we attempt to review some of the primary entities in nail pathology with the aid of modern interpretations of nail histology and embryology. We also provide diagrams that can aid in comprehending this field of pathology.

CD30 in Cutaneous Pathology.

ABSTRACT: The discovery of CD30 as a diagnostic marker was essential in the identification of not only some lymphomas but also many other solid tumors and benign reactive conditions. Many CD30+ cutaneous disorders and tumors have been categorized since the identification of the marker. With the design of targeted therapies against CD30+ tumoral cells, the interest in CD30 determination was not only diagnostic but also mainly therapeutic. In this article, we explore the historical aspects of the discovery of CD30 and examine the main CD30-related cutaneous pathology, susceptible of anti-CD30 modern treatments.

The Dermatopathology Books Before Unna.

ABSTRACT: Unna's book on dermatopathology was the one that achieved the greatest recognition in medicine and influenced the largest number of dermatopathologists in Europe at that time. However, several previous texts also gathered the requirements to be considered dermatopathological books. In this manuscript, we briefly examine some of the most relevant features of the dermatopathology books written by Simon, Leloir and Vidal, Auspitz, Bärensprung, and Jackson.

Connexin 43 in Dermatofibroma and Dermatofibrosarcoma Protuberans: Diagnostic, Pathogenic, and Therapeutic Implications.

ABSTRACT: Connexins play a crucial role in the formation of gap junctions that connect cells to each other, as well as cells to the surrounding environment. In recent years, connexin 43 has been extensively studied in various human tumors. In this study, we conducted an immunohistochemical analysis to evaluate the expression of connexin in 16 dermatofibromas (DFs) and 13 dermatofibrosarcoma protuberans (DFSP). Connexin was diffusely expressed in the cytoplasm of all DFs with moderate or strong intensity, whereas all DFSPs showed negative staining. In addition to its diagnostic implications, the loss of Cx43 may elucidate the invasive capacity of DFSP and offer a potential avenue for future therapeutic interventions.

Ungual Keratoacanthoma With Features of Regression.

ABSTRACT: Ungual keratoacanthoma (UKA) is an infrequent tumor. Different from keratoacanthoma in other parts of the skin, UKA rarely regresses, and grows aggressively with common destruction of the subjacent phalanx. Reported cases of UKA with features of regression are exceptional, and even dermatopathologists with reputed experience in nail pathology admit to having seen very few cases. We herein report a case of a 77-year-old man who presented a painful subungual lesion on the second finger of the right hand. An x-ray showed evidence of erosion of the subjacent distal phalanx. The patient was highly concerned about the lesion and rejected conservative treatment preferring amputation of the distal phalanx. The histopathologic examination revealed a UKA with features of regression.

Axillary Cutaneous Hemosiderosis in a Patient With Hyperhidrosis, After Intravenous Iron Infusion.

ABSTRACT: Hemosiderosis consists of an iron deposit in tissues, which does not cause organic damage to them. However, in the case of the skin, being an organ exposed to sight, siderosis can produce a brownish coloration that is aesthetically discomforting for the individual. Most cutaneous sideroses are because of venous insufficiency with hemorrhagic extravasation. There is also a group secondary to iron extravasation in the injection site of the transfusion. However, there are very few cases in which an intravenous injection of an iron preparation has produced diffuse siderosis in extensive areas of the skin. We present the case of a 31-year-old woman with hyperhidrosis, who was transfused as a result of postpartum hemorrhage and, shortly after receiving an intravenous iron infusion, developed extensive hyperpigmentation in both axillae.

Post-Transplant Lymphoproliferative Disorder, Monomorphic Type, in a Kidney Transplant Patient After Administration of Anti-Influenza Vaccine.

ABSTRACT: Post-transplant lymphoproliferative disorders (PTLD) are rare complications in solid organ transplant patients. Their pathogenesis is largely unknown and closely linked to low immunity, which allows uncontrolled lymphocyte proliferation. Although transplant patients receive annual influenza vaccination as a preventive protocol, we have not found any cases where the flu vaccine triggered a PTLD. We present the case of a 49-year-old female kidney transplant recipient who developed an Epstein-Barr virus-negative PTLD, CD30 + anaplastic monomorphic type, ALK-, which presented the day after a single dose of anti-influenza vaccine. The initial clinical presentation was subcutaneous, but imaging studies revealed multiorgan involvement.

Novel uses of laser therapy in Goltz syndrome.

Goltz syndrome is an X-linked dominant, multisystem birth defect due to PORCN mutation. The skin findings follow Blaschko's lines and often show epidermal atrophy and herniation of subcutaneous fatty tissue. Regarding treatment, light sources can offer a good therapeutic option for some manifestations of this rare disease and improve the aesthetic appearance of the skin lesions. We report two new cases of Goltz syndrome in which the cutaneous findings remarkably improved with pulsed dye laser and carbon dioxide laser.

Frontal Fibrosing Alopecia and Sunscreen Use: A Cross-sectional Study of Actinic Damage.

Patients with frontal fibrosing alopecia report higher rates of sunscreen use than control subjects. However, it is not known whether the higher use of sunscreens is a cause or a consequence of the alopecia. A greater use of sunscreens should be associated with a lower incidence of signs of actinic damage. The aim of this study is to assess the presence of actinic damage in patients with frontal fibrosing alopecia. A cross-sectional study was carried out on 101 patients with frontal fibrosing alopecia and 40 control subjects. The presence of actinic damage, in the form of solar lentigines, actinic keratoses, and basal and squamous cell carcinomas, was recorded in both groups, together with sunscreen use. Trichoscopy and skin biopsy were performed on patients. Actinic damage was present more frequently in patients with frontal fibrosing alopecia (69.3%) than in control subjects (50%) (p = 0.031). Patients used sunscreens more frequently than did control subjects (83.2% vs 62.5%, p = 0.008). However, the prevalence of trichoscopic inflammatory signs, peripheral alopecia, and inflammatory infiltrate and sebaceous gland involvement in skin biopsy, were similar in patients who used sunscreens and those who did not use them. In conclusion, patients with frontal fibrosing alopecia had greater actinic damage than did control subjects, and this is hypothesized as a reason for the higher use of sunscreens among patients. Thus, use of sunscreens may not be the trigger for frontal fibrosing alopecia that dermatologists have proposed.

Pigmented Multinucleate Cell Angiohistiocytoma: First Case.

ABSTRACT: Multinucleate cell angiohistiocytoma (MCAH) is a benign vascular and fibrohistiocytic (probably reactive) proliferation with peculiar multinucleate cells which most authors interpret as degenerated macrophages. Several clinical variants of MCAH have been described, some of them with brownish-appearing lesions clinically. However, no histologically identified pigment has been described in the cytoplasm of the multinucleate cells so far. We present a pigmented MCAH with cytoplasmic brownish pigment, which was positive with a Masson-Fontana stain and negative with an iron stain, consistent with melanin, in a 33-year-old woman with multiple papules and plaques on the right elbow, right jawline, and left flank.

Genetic Studies on a Case of Eruptive Disseminated Spitz Nevus and Review of Other 33 Cases.

ABSTRACT: Eruptive disseminated Spitz nevus is an uncommon presentation of Spitz nevi. Only a few tens of cases have been published and only 6 of them have genetic studies. We present an additional case of a 29-year-old woman with dozens of Spitz nevi which had appeared since she was aged 10 years. The nevi were located on arms, inner thighs, legs, and buttocks. Nine of them were biopsied. Four presented severe atypia. Immunohistochemistry was performed on 5 of the biopsied specimens and was negative for PRAME, ROS-1, PDL-1, pan-TRK, and ALK. Molecular studies on the largest lesion demonstrated no NTRK1, NTRK2, or NTRK3 fusions. FISH study for PTEN showed no alteration in that same lesion. Next-generation sequencing was also negative for any detectable mutations in numerous genes analyzed. In conclusion, it seems reasonable to be cautious when evaluating atypia, even if severe, in cases of eruptive disseminated Spitz nevus.

Varicella Zoster With Pemphigus-like Reaction.

ABSTRACT: We present a case of a 55-year-old man with a rash on his right foot that was biopsied and diagnosed as a Varicella Zoster virus infection with an accompanying positive immunohistochemical study with antiviral antibodies. He concomitantly suffered from a Varicella Zoster virus meningitis. The skin biopsies not only showed clear histologic signs of viral cytopathic effects but also showed intercellular IgG and C3 intraepidermal staining by direct immunofluorescence study, findings which are typically consistent with pemphigus vulgaris. However, the patient did not have any history of pemphigus; there was no mucosal involvement, and serum antibodies to desmoglein 1 and 3 were negative. After discharge, the patient continued to have right-sided foot pain, and he continued the acyclovir treatment.

Connexin 43 Expression in Cutaneous Biopsies of Lupus Erythematosus.

INTRODUCTION: Gap junctions are channels between adjacent cells formed by connexins (Cxs). Cxs also form hemichannels that connect the cell with its extracellular milieu. These channels allow the transport of ions, metabolites, and small molecules; therefore, Cxs, and more specifically, connexin (Cx) 43 has been demonstrated to be in control of several crucial events such as inflammation and cell death. MATERIAL AND METHODS: We examined the immunostaining of Cx43 in the endothelia of the cutaneous blood vessels of biopsies from 28 patients with several variants of lupus erythematosus. RESULTS: In 19 cases (67.86%), staining of more than half of the dermal vessels including both vessels of the papillary and of the reticular dermis was identified. Only in 4 cases (14.28%), less than 25% of the vessels in the biopsy showed expression of the marker. CONCLUSIONS: Our results suggest a role of Cx43 in regulating the endothelial activity in lupus erythematosus, which also opens a door for targeted therapeutic options.

Pulse Granuloma-Like Reaction on the Forearm Following an Accidental Wound.

ABSTRACT: Pulse granulomas are uncommon reactions to vegetable exogenous matter characterized by the presence of hyaline rings. Although they are usually found in the oral cavity or along the gastrointestinal or respiratory tracts, there are a few cases described outside those regions. We present the first case of a granulomatous reaction with hyaline rings in the skin reaction after an accidental wound and suggest the term pulse granuloma-like to describe lesions that resemble pulse granulomas but with no connection to the gastrointestinal or respiratory tracts. Moreover, we provide a graphic comparison of the hyaline rings observed in our case and the histologic sections of some plants that could have been involved.

Thickening of the basement membrane as a diagnostic sign of mycosis fungoides.

The epidermal basement membrane (BM) is readily identified on skin biopsy specimens stained with periodic acid-Schiff (PAS) and PAS with diastase (PAS-D). Thickening of BM can be evidenced in several inflammatory and tumoral conditions. We noticed that most of our biopsy specimens of mycosis fungoides (MF) showed thickening of the BM. We decided to retrospectively study BM thickness in 27 biopsy specimens of MF and compare them with 27 cutaneous biopsy specimens of inflammatory diseases. We studied PAS and PAS-D stains in all cases and we measured BM thickness with an ocular micrometer. Cases were scored in a four-tiered system: 0: no detectable staining; 1+ (mild: < 5 µm); 2+ (moderate: 5-9 µm); and 3+ (prominent: >9 µm). The difference between both groups (MF vs controls) was highly significant for BM thickness values by both one- and two-tailed t tests (P < 0.0006). While only 3 biopsy specimens from the controls (11.11%) showed areas of 3+ thickening, 12 biopsy specimens of MF (44.44%) showed areas of 3+ thickening, and most cases showed diffuse, at least 2+ thickening, while the controls showed more segmental, mostly 1 or 2+ staining. We conclude that thickening of BM can be useful in the differential diagnosis with inflammatory conditions.

Lichen-planopilaris-like scarring pattern in a patient with alopecia and pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP) is an erythematous-desquamative dermatitis that is sometimes associated with non-scarring alopecia. Despite the fact that the disease can be disfiguring, scarring alopecia has rarely been described in this disease. Here, we present a 69-year-old woman who developed an erythrodermic episode of PRP associated with telogen effluvium that left an area of persistent alopecia of the scalp and resulted in hair loss in the eyebrows. The biopsy of that area of the scalp demonstrated a scarring alopecia with lichen-planopilaris-like features. Despite this histopathology, the alopecia responded well to treatment. This finding expands the context in which lichen planopilaris features can be found and demonstrates their good prognosis under early treatment.

Porocarcinoma with areas of mucinous differentiation suggesting multilineage differentiation.

Porocarcinoma is an infrequent malignant adnexal carcinoma, with some histopathological variants described, such as the clear cell, the sarcomatoid or the pigmented porocarcinoma. We report an invasive porocarcinoma showing areas of tumor cells floating in prominent dermal mucin, simulating mucinous carcinoma, that we consider a new histopathological variant of porocarcinoma. We report a 74-year-old male with previous history of multiple basal cell carcinomas that presented a nodule on his left temple. Histopathologic study showed a large ulcerated multilobular tumor composed of thickened cords of cells emanating from a hyperplastic epidermis and showing a mixed infiltrative and pushing pattern in the dermis. Poroid differentiation was observed in most of the neoplasm, both in intraepidermal and dermal invasive component. Within the neoplasm a prominent area where these small nests with clear formation of ducts were floating in mucinous pools with few septa intermingled was observed, simulating a primary cutaneous mucinous carcinoma. Cytology, immunohistochemistry and the presence of both neoplastic areas as closely related and with multiple points of connectivity favors the consideration of a composite tumor in this peculiar case. Other differentials are discussed.