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Atypical fibroxanthoma is a rare mesenchymal skin tumor of intermediate malignancy that typically occurs on sun-damaged skin of elderly patients. Histologically, it is composed of pleomorphic cells with hyperchromatic nuclei and abundant cytoplasm, commonly arranged in a spindle cell pattern. Different histologic variants have been described during the past years. We present a case of atypical fibroxanthoma containing a dense inflammatory infiltrate, which in conjunction with the existence of immunoblast-like and Reed-Sternberg-like neoplastic cells could be misinterpreted as a lymphoid neoplasm. Immunohistochemical studies revealed strong positivity of tumor cells for CD10 and negativity for cytokeratins, p63, p40, S100, SOX10, ERG, actin, desmin, B and T-cell markers, BCL6, CD15, and CD30. The inflammatory infiltrate contained a mixed reactive T- and B-cell population with negative T-cell receptor and immunoglobulin heavy rearrangements. We discuss the differential diagnosis of this entity in which clinical, immunohistochemical, and molecular features are essential to avoid the diagnosis of a lymphoproliferative disease.

Tattoos are characterized by the introduction of exogenous pigments into the dermis. Tattoos usually serve cosmetic purposes, although they may have other causes, such as traumatic pigment implants in accidents or medical-related tattoos in the context of radiotherapy. Dermatologic adverse reactions are relatively uncommon, and they include infections, immune-mediated reactions, cutaneous lesions secondary to the Koebner phenomenon, exacerbation of preexisting dermatosis, benign and malignant neoplasms, and a miscellaneous group of dermatologic conditions that may appear in a preexisting tattoo. The aim of this study is to review the types of histopathologic reactions that may appear in a preexisting permanent tattoo.

Background The introduction of immune checkpoint inhibitors (ICI) has improved the survival outcomes of patients with advanced melanoma. To date, only a few studies have evaluated the immunohistochemical (IHC) expression of PD-1 and CTLA-4 in tumor-infiltrating lymphocytes (TILs) as predictive markers of response to ICI, most of them in the context of clinical trials. Moreover, the predictive value of PD-L1 in melanoma cells in the response to immunotherapy is unclear. The aim of our study was to assess the IHC expression of PD-L1, PD-1, and CTLA-4 in samples of patients with advanced melanoma and to establish their prognostic value as predictors of ICI response in a university hospital. Methods The expression of PD-L1, PD-1, and CTLA-4 was evaluated in pretreatment tumor samples in a series of 35 patients, 21 patients treated with nivolumab and 14 patients with ipilimumab in monotherapy. Results In the nivolumab group, 4 tumors (19%) were positive for PD-L1 and all of them showed a partial response to the treatment. However, 4 patients whose tumors did not express PD-L1 also responded to nivolumab. PD-1 expression was not associated with better progression-free survival (PFS). In the ipilimumab group, 5 patients (35.7%) showed expression of CTLA-4. Positive cases showed a better PFS; however, one negative case responded to ipilimumab. Conclusions Nivolumab produces a better response compared with ipilimumab in patients with melanoma. The IHC expression of PD-L1 and CTLA-4 are associated with a higher response rate to nivolumab and ipilimumab, respectively, and better PFS, but the existence of responder patients with negative expression suggests that they are not adequate biomarkers to select candidate patients for ICI in the clinical practice.

Graft-versus-host disease (GVHD) is one of the most common and serious complications of hematopoietic stem-cell transplantation that mainly affects the skin, gastrointestinal tract, and liver. Hepatic GVHD is associated with high morbidity and mortality, and its diagnosis can be especially challenging because of nonspecific clinical signs and symptoms. It must be suspected in patients with elevated liver enzymes and cholestasis, especially in those with a history of preceding skin rash and diarrhea. We describe 3 patients with cutaneous and hepatic GVHD that presented with severe hypercholesterolemia and hypertriglyceridemia, and no xanthomatous macular lesions, in which cutaneous biopsies revealed the presence of xanthomatous dermal histiocytes. We propose that the presence of these xanthomatous cells in skin biopsies from patients with cutaneous GVHD could be a dermatopathological clue for the diagnosis of hepatic GVHD.

Allogeneic hematopoietic stem-cell transplantation and solid-organ transplantation are associated with an increased risk of secondary neoplasms. Indeterminate cell histiocytosis (ICH) is a rare disease composed of so-called indeterminate cells, an alleged cutaneous dendritic cell subset displaying histological and some ultrastructural and immunophenotypic features of Langerhans cells but lacking Birbeck granules. We report a case of cutaneous ICH occurring after allogeneic hematopoietic stem-cell transplantation for a myelodysplastic syndrome in a 56-year-old man. Microsatellite analysis demonstrated that the neoplastic cells were derived from the donor's hematopoietic system. This case broadens the spectrum of complications after stem-cell transplantation and demonstrates that cutaneous ICH in the setting of myelodysplastic syndromes may have a nonrelated origin to dysplastic myeloid cells.

We review the most characteristic clinical and histopathologic findings of the cutaneous manifestations of the occlusive nonvasculitic vasculopathic disorders. Clinically, most of these conditions are characterized by retiform purpura. Histopathologic findings consist of occlusion of the vessel lumina with no vasculitis. Different disorders may produce nonvasculitic occlusive vasculopathy in cutaneous blood and lymphatic vessels, including embolization due to cholesterol and oxalate emboli, cutaneous intravascular metastasis from visceral malignancies, atrial myxomas, intravascular angiosarcoma, intralymphatic histiocytosis, intravascular lymphomas, endocarditis, crystal globulin vasculopathy, hypereosinophilic syndrome, and foreign material. Other times, the occlusive disorder is due to platelet pugging, including heparin necrosis, thrombocytosis secondary to myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, and thrombotic thrombocytopenic purpura. Occlusive vasculopathy may also appear in cold-related gelling agglutination, like that occurring in cryofibrinogenemia, cryoglobulinemia, cold agglutinin syndrome, and crystalglobulinemia. Microorganisms may also occlude the vessels lumina and this is especially frequent in ecthyma gangrenosum, opportunistic fungi as aspergillosis or fusariosis, Lucio phenomenon of lepromatous leprosy and disseminated strongyloidiasis. Systemic coagulopathies due to defects of C and S proteins, coumarin/warfarin-induced skin necrosis, disseminated intravascular coagulation, and antiphospholipid antibody/lupus anticoagulant syndrome may also result in occlusive nonvasculitic vasculopathy. Finally, vascular coagulopathies such as Sneddon syndrome, livedoid vasculopathy, and atrophic papulosis may also cause occlusion of the vessels of the dermis and/or subcutis. Histopathologic study of occlusive vasculopathic lesions is the first step to achieve an accurate diagnosis, and they should be correlated with clinical history, physical examination, and laboratory findings to reach a final diagnosis.

Therapies targeting the BRAF oncogene have improved the overall and disease-free survival of patients with advanced melanomas. An unresolved issue in clinical practice is the existence (or not) of BRAF-mutated and BRAF-nonmutated tumors in individual patients (intrapatient BRAF mutation heterogeneity), which may serve as a mechanism of resistance to BRAF inhibitors or lead to diagnostic problems. Different research groups have reported differing results after analyzing the BRAF mutation statuses of multiple melanoma tumors. Herein, we present a brief revision of the literature on this controversial topic and propose a theory to justify the divergence of the results found in the literature.

Pagetoid dyskeratosis (PD) is an incidental pathologic finding that appears in several skin conditions. In an attempt to better understand PD and its incidence in dermatopathology, the authors have analyzed all skin biopsies performed over the period of 1 year in our Department of Dermatology and examined their clinical and dermatopathological variables. The criteria used for a keratinocyte to be considered a PD cell were: (1) a size larger than normal, (2) the presence of pycnotic nucleus, (3) a clear halo surrounding the nucleus, and (4) a pale eosinophilic cytoplasm. A total of 3565 biopsies were analyzed, PD cells being found in 80 cases (2.24%). Melanocytic nevi were the commonest skin lesions in which PD was observed, followed by soft fibromas, angiofibromas, and acrochordons. Most lesions were located on the head, neck, and trunk. Most cases displayed fewer than 15 PD cells per field. PD cells were normally located in the mid epidermis (frequently in clusters). The biopsies usually revealed indirect signs of rubbing, although PD cells were also found in places where rubbing was unlikely. Here, the authors report the largest series of PD analyzed to date, expanding our understanding of this striking pathological observation.

Follicular mucinosis coexisting with lymphoproliferative disorders has been thoroughly debated. However, it has been rarely reported in association with inflammatory disorders.Thirteen cases have been retrieved, and those with cutaneous lymphoma or alopecia mucinosa were excluded.Follicular mucinosis was found in the setting of squamous cell carcinoma, seborrheic keratosis, simple prurigo, acne vulgaris, dextrometorphan-induced phototoxicity, polymorphous light eruption (2 cases), insect bite (2 cases), tick bite, discoid lupus erythematosus, drug-related vasculitis, and demodecidosis. Unexpectedly, our observations revealed a preponderating accumulation of mucin related to photo-exposed areas, sun-associated dermatoses, and histopathologic solar elastosis. The amount of mucin filling the follicles apparently correlated with the intensity of perifollicular inflammatory infiltrate, which was present in all cases. The concurrence of dermal interstitial mucin was found in 7 cases (54%).The concurrence of interstitial dermal mucinosis or the potential role of both ultraviolet radiation and the perifollicular inflammatory infiltrates in its pathogenesis deserves further investigations. Precise recognition and understanding of this distinctive, reactive histological pattern may prevent our patients from unnecessary diagnostic and therapeutic strategies.

Dermatofibromas (DFs) are common benign fibrohistiocytic lesions, mostly affecting young adults. Many types of DF have been described, depending on architectural, cellular, and stromal peculiarities. Recently, a peculiar type of benign cutaneous tumor showing hemosiderotic DF-like stroma and apocrine glands has been described. We report 2 additional cases of DF without hemosiderotic changes showing entrapped apocrine glandular structures. We speculate about the origin of the glandular component and propose the term adenodermatofibroma for this type of lesions.

Although spindle cell carcinoma (SC) is a common neoplasm in the oral cavity, upper respiratory tract, and other head and neck areas, its occurrence in the vulva is rare. We report a case of this rare condition with immunohistochemical, ultrastructural, and human papillomavirus (HPV) testing. The neoplastic cells were positive for vimentin, keratins (AE1-AE3, keratin 902, and keratin 903), and epithelial membrane antigen. Ultra-structurally, they showed primitive junctions and tonofilaments. HPV testing by polymerase chain reaction was negative. In addition, we review the clinicopathologic findings of the four well-documented cases of vulvar SC that have been reported previously in the English language literature.

Circumscribed palmar and plantar hypokeratosis (CPPH) is a recently described skin condition with particular clinical and histopathological findings. The etiopathogeny of CPPH is still unclear, but an abnormal clone of keratinocytes has been postulated as the possible origin. CPPH has been considered an entity with no potential malignant transformation, but recently, it has been recognized in association with signs of actinic keratosis in the same biopsy. CPPH has never been recognized in association with porokeratosis. Although these entities seem to be different, a possible relationship between them might be suggested.

Dermatofibrosarcoma protuberans (DFSP) is a dermal and subcutaneous slow-growing tumor of intermediate malignancy. Different histological variants of DFSP have been described, depending on cellular and stromal peculiarities. Here, we report the histological features of a DFSP in which cells were frequently arrayed in cords and fascicles that were interweaved, conforming a peculiar braided pattern. This finding might pose difficulties in the differential diagnosis with neural neoplasms and expands the morphological spectrum of DFSP.

Papular-purpuric "gloves and socks" syndrome is a distinctive dermatosis featuring acral pruritus, edema, and petechiae. It has been attributed in most--but not all--reported cases to Parvovirus B19 infection, on the grounds of serological proof of recent infection or detection of viral DNA by polymerase chain reaction in patient serum or biopsies. We report the immunohistochemical detection of Parvovirus B19 VP2 structural protein in the endothelial lining of dermal blood vessels in 3 examples of Papular-purpuric "gloves and socks" syndrome and review previously described immunohistochemical investigations in cutaneous involvement by this infection.

Amyloid elastosis is a rare form of cutaneous amyloidosis characterized histologically by the deposition of amyloid-coating elastic fibers of the skin. To date, only 4 cases have been reported, all of them in the setting of systemic amyloidosis. We present the first case of primary cutaneous localized amyloid elastosis.

Adenolipoma is a rare microscopic variant of cutaneous lipoma composed of large lobules of mature adipocytic tissue admixed with eccrine ducts and glands. We report a new case of cutaneous adenolipoma, and the first showing an apocrine cystic glandular component. This lesion may not be a specific entity, and could represent entrapment of epithelial structures within a lipoma.

A poroma is a benign neoplasm composed of poroid and cuticular cells and is thought to derive from the eccrine duct. Several recent reports have described cases with sebaceous, follicular, and apocrine differentiation, suggesting a possible apocrine origin, however. Trichoblastoma is a rare benign tumor composed of germinative cells related to the folliculosebaceous-apocrine unit. We report a unique case of a trichoblastoma arising within a poroma with apocrine and sebaceous differentiation. To our knowledge, this exceptional association has not been described previously and may support the theory of the apocrine origin of poromas.