Deep Reticular Dermis Research Articles

E034 Drug-induced accelerated nodulosis in a patient with rheumatoid arthritis

Abstract Background/Aims Drug-induced accelerated nodulosis (DIAN) is characterized by the occurrence or progression of multiple subcutaneous nodules in a patient treated for rheumatoid arthritis (RA). It was first and most commonly reported with methotrexate in RA patients. Methods A 37-year-old normotensive, non-diabetic, seropositive rheumatoid arthritis female presented with complaints of nodules over the bilateral hands and feet from the last three months. The treatment history included methotrexate therapy (10 mg/week) for one year. Methotrexate-induced rheumatoid accelerated nodulosis (MIAN) was suspected. Methotrexate was stopped and hydroxychloroquine was added considering the low disease activity. The nodules decreased in number as well as size. On follow-up, she presented with increased multiple joint pain and swelling with ESR 60 mm/hour, CRP 13.6 mg/L, and leflunomide was added. After six months of leflunomide use, she again developed multiple bilateral nodules on the extensor and palmar surface of fingers and feet, ranging from 0.5 to 1 cm. The CRP was 9.2 mg/L, ESR 80 mm/hour, complete blood count showed mild anaemia with normal renal and liver function tests. The nodule biopsy showed palisading granuloma consisting of lymphocytes and histiocytes in mid and deep reticular dermis with large foci of fibrin deposition and collagen degeneration s/o rheumatoid nodule. Leflunomide was stopped. Results The leflunomide was switched to sulfasalazine along with colchicine, and hydroxychloroquine was continued. The patient is doing well on follow-up in terms of disease activity and nodule size. Palmeiro. A.G., et al. 2022 reviewed 39 studies from 1st Jan 1988 to 1st Jan 2022 and found 109 cases of accelerated nodulosis. 99 patients had RA, methotrexate was the culprit drug in 89, followed by etanercept in 7 and leflunomide was in just 3 patients. Although there are no exact treatment guidelines, tumour necrosis factor inhibitors were avoided due to increased nodulosis risk. Recently, Valor-Méndez. L., et al 2020 reported improved nodulosis with Janus Kinase inhibitors like baricitinib, which seems to be a future option. Histologically, rheumatoid nodules and accelerated nodulosis are indistinguishable. The exact pathogenesis is unknown but, polymorphic variants of methionine synthase reductase or haplotype HLA-DRB1*0401, and adenosine A1 receptor promotion in multinucleated giant cells are associated. Conclusion Drug-induced accelerated nodulosis (DIAN) and MIAN are not that rare but diagnosis is challenging. It causes significant morbidity and affects the quality of life because of the predominant involvement of hands and feet. It should be suspected especially when disease activity is low or rapidly progressive nodules with a change in immunotherapy. Partial to total improvement can be achieved by identifying and stopping the culprit drug. We need specific guidelines, more treatment options, and a specific national registry to report such adverse effects with biologics and non-biologic disease-modifying antirheumatic drugs. Disclosure H. Singh: None. R. Kaur: None. G. Mohan: None.

Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences.

Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.

Amplification of Mutant NRAS in Melanocytic Tumors With Features of Spitz Tumors

NRAS activating mutations are prevalent in melanocytic neoplasia, occurring in a subset of common acquired melanocytic nevi and ∼30% of cutaneous melanomas. In this study, we described a cohort of 7 distinctive melanocytic tumors characterized by activating point mutations in codon 61 of NRAS with amplification of the mutant NRAS allele and shared clinicopathologic features. These tumors occurred predominantly in younger patients, with a median age of 20 years (range, 6-56 years). They presented as papules on the helix of the ear (4 cases) or extremities (3 cases). Microscopically, the tumors were cellular, relatively well-circumscribed, compound, or intradermal proliferations. The tumor cells often extended into the deep reticular dermis and involved the superficial subcutaneous fat in some cases. The melanocytes were epithelioid to spindled with moderate amounts of cytoplasm and conspicuous nucleoli. They were arranged in short plexiform fascicles, nests, and cords. Some cases had occasional pleomorphic and multinucleated melanocytes. Rare dermal mitotic figures were present in all cases. The dermis contained thick collagen bundles and minimal solar elastosis. Follow-up data were available for 5 patients, with a median period of 4.2 years (range, 1-9 years), during which no recurrences or metastases were reported. Our series highlights a clinicopathologically and molecularly distinctive subset of NRAS-mutated tumors with amplification of the mutant NRAS allele.

P11 Acrodermatitis chronica atrophicans: a sign of late lyme disease

Abstract Borrelia infection manifests a variety of signs and symptoms, and its insidiousness and heterogeneity mean that its diagnosis can be delayed. We describe two patients from south-east Scotland who presented with unilateral asymptomatic atrophic areas of skin discoloration. The first was a 71-year-old woman, who presented with a 4-month history of a nonprogressive, mottled, erythematous rash involving her right thigh, buttock and calf. Case 2 was a 56-year-old woman with a 2-year history of an erythematous area of atrophic skin involving the medial aspect of her left thigh and shin. Histology from case 1 showed a normal epidermis with a largely ‘top-heavy’ superficial and deep, predominantly interstitial and focally perivascular, lymphohistiocytic infiltrate, with a predominance of mononuclear histiocytes and with focal extension to deep reticular dermis. Scattered plasma cells were identified, but eosinophils were not a prominent feature. Well-formed granulomas were absent, as were interface dermatitic activity and vasculitic changes. On close questioning, each patient remembered ‘insect’ bites in the vicinity of the cutaneous changes, although neither recalled rashes that could have been consistent with erythema chronicum migrans. In both cases, serology confirmed infection with Borrelia burgdorferi (sensu lato) and diagnoses of acrodermatitis chronica atrophicans (ACA) were made. Both patients responded well to oral treatment with doxycycline. ACA is a cutaneous sign of late-stage Lyme disease and is caused by ongoing active skin infection by tick-borne bacteria of the Lyme disease group of Borrelia species. The tick bite has usually occurred months or years before symptom onset. Typically, there is an early, unilateral inflammatory stage with bluish-red discoloration of the skin and an oedematous appearance. This is followed by an atrophic stage where the skin becomes thin and wrinkled (‘cigarette paper’-like), with the loss of epidermal and dermal structures. Histological features usually include marked atrophy of the epidermis and dermis, loss of adnexal structures and an absence of elastic tissue. A band-like lymphocytic infiltration with plasma cells and mast cells is seen in the dermis, especially in the early stage of disease. Laboratory-confirmed cases of Lyme borreliosis in the UK have risen steadily since reporting began in 1986. ACA is likely to be underdiagnosed and, if there is a clinical suspicion, a detailed history, careful skin examination, Borrelia serology and skin biopsy should be undertaken. Early recognition and treatment reduce the risk of irreversible skin changes and systemic symptoms.

Pseudoxanthoma elasticum: a rare case report

<p class="abstract">Pseudoxanthoma elasticum (PXE) is a hereditary systemic connective tissue disease affecting mainly the skin, retina and cardiovascular system. Pathologically, it is characterized by mineralization and fragmentation of elastic fibers (so-called "elastorhexia"). PXE is associated with mutations in the ABCC6 (ATP binding cassette subtype C number 6) gene. Women are affected more than men. A 22-year-old woman came to our department with complaints of small, yellowish raised lesions in rows or lacy pattern on her neck since 2 years, some of which coalesced to form larger lesions. She also complains that the skin has been soft, flabby, and wrinkled since 2 years in the armpits, trunk, groin, and knees. On examination, the lesions were slightly pebbly in appearance; such papular lesions tend to coalesce gradually to form plaques with a cobblestone appearance. On histopathological examination, elastic fibers appear basophilic due to calcium deposition. The fibers were fragmented, swollen, and clustered in the middle and deep reticular dermis. The collagen fibers were split. Based on the above findings, a diagnosis of PXE was made. Due to the rarity of the disease, we are reporting this case. The course and prognosis were explained to the patient. Most of the pathological changes associated with PXE are irreversible, but prophylactic measures can be taken to minimize the course of the disease.</p>

Scleredema diabeticorum.

Scleredema of Buschke is a rare connective tissue disease with a poorly understood pathogenesis. Three types of scleredema have been distinguished according to its association with preceding or underlying conditions. Type 1 is usually secondary to a febrile infection, type 2 is mostly associated with paraproteinemia and type 3, usually named scleredema diabeticorum, has a strict association with Diabetes mellitus. A diffuse, non-pitting swelling and induration of the skin define this disease. The skin histology is characterized by a normal or slightly thinned epidermis, and the dermis containing a decreased number of elastic fibers and thick large swollen collagen bundles separated by mucopolysaccharide deposits in the deep reticular dermis. In this report we present a 58-year-old man with scleredema diabeticorum controlled with a topical steroid cream and an optimization of glycemic control. We reviewed clinical, histopathological characteristics and the various possible treatments.

Conventional and Atypical Deep Penetrating Nevus, Deep Penetrating Nevus-like Melanoma, and Related Variants.

Simple SummaryAtypical deep penetrating nevus (DPN) is a unique skin tumor with an uncertain biologic/metastatic potential that may be difficult to distinguish from DPN (an indolent lesion) and DPN-like melanoma (an aggressive lesion) based on the results of histomorphologic analysis and commonly employed molecular studies such as fluorescence in situ hybridization and comparative genomic hybridization alone. Herein, we review the clinical, histomorphological, immunohistochemical, molecular, and cytogenetic characteristics of the DPN spectrum of lesions to try to better understand the prognosis of these lesions and possible treatment approaches.Deep penetrating nevus (DPN) is an uncommon acquired melanocytic lesion with a distinct histopathological appearance that typically behaves in an indolent manner. The lesion is characterized by a symmetrical proliferation of epithelioid to spindled melanocytes associated with abundant melanophages and wedge-shaped extension to the deep reticular dermis and subcutis. Pronounced cytologic atypia and mitotic figures are usually absent, which helps distinguish DPN from melanoma with a deep penetrating growth pattern. Recently, the concept of atypical DPN has been proposed for lesions that demonstrate borderline histomorphologic features and may be associated with lymph node deposits but lack the copy number aberrations typical of melanoma by either fluorescence in situ hybridization or comparative genomic hybridization. While most of these lesions have a favorable clinical course, rare lesions may progress to melanoma. In this review, we summarize the current literature on atypical DPNs with uncertain behavior/metastatic potential and outline the characteristics that distinguish these lesions from conventional DPN and melanoma with DPN-like features.

Neonatal lupus erythematosus exacerbated by vaccination.

Neonatal lupus erythematosus (LE) is a rare immune-mediated disease caused by placental transport of maternal anti-SSA/Ro, anti-SSB/La and/or anti-U1RNP antibodies. Here, we demonstrate two cases of neonatal LE, in both of which cutaneous LE was exacerbated by inoculation. To our knowledge, cases worsening neonatal LE after administration of vaccines have not been reported. In case 1, not only exacerbation of pre-existing annular erythema but also spreading of new erythematous lesions to the trunk and extremities were induced following vaccination. Of interest, all of the lesions simultaneously improved. By contrast, in case 2, pre-existing facial erythema became prominent without spreading to other sites. The mother of case 1 had Sjögren's syndrome, whereas in case 2, the mother was diagnosed with Sjögren's syndrome on this occasion for the first time. Immunohistochemistry in case 1 revealed interleukin (IL)-17-positive cells infiltrating into the papillary dermis, and CD123-positive plasmacytoid dendritic cells in the papillary dermis and the deep reticular dermis. Both innate immune response and IL-17 mediated inflammation following vaccination are speculated as a possible mechanism of the deterioration of LE lesions in our juvenile cases. Caution is necessary since neonatal LE can be worsened following vaccination.

Heterogeneity of fibrillin-rich microfibrils extracted from human skin of diverse ethnicity.

The dermal elastic fibre network is the primary effector of skin elasticity, enabling it to extend and recoil many times over the lifetime of the individual. Fibrillin-rich microfibrils (FRMs) constitute integral components of the elastic fibre network, with their distribution showing differential deposition in the papillary dermis across individuals of diverse skin ethnicity. Despite these differential findings in histological presentation, it is not known if skin ethnicity influences FRM ultrastructure. FRMs are evolutionarily highly conserved from jellyfish to man and, regardless of tissue type or species, isolated FRMs have a characteristic 'beads-on-a-string' ultrastructural appearance, with an average inter-bead distance (or periodicity) of 56nm. Here, skin biopsies were obtained from the photoprotected buttock of healthy volunteers (18-27years; African: n=5; European: n=5), and FRMs were isolated from the superficial papillary dermis and deeper reticular dermis and imaged by atomic force microscopy. In the reticular dermis, there was no significant difference in FRM ultrastructure between European and African participants. In contrast, in the more superficial papillary dermis, inter-bead periodicity was significantly larger for FRMs extracted from European participants than from African participants by 2.20nm (p<.001). We next assessed whether these differences in FRM ultrastructure were present during early postnatal development by characterizing FRMs from full-thickness neonatal foreskin. Analysis of FRM periodicity identified no significant difference between neonatal cohorts (p=.865). These data suggest that at birth, FRMs are developmentally invariant. However, in adults of diverse skin ethnicity, there is a deviation in ultrastructure for the papillary dermal FRMs that may be acquired during the passage of time from child to adulthood. Understanding the mechanism by which this difference in papillary dermal FRMs arises warrants further study.

Histopathological Features of Subcutaneous Sarcoidosis.

Only a few series of patients with systemic sarcoidosis and specific subcutaneous lesions have been reported. We reviewed our patients with systemic sarcoidosis with specific subcutaneous lesions to analyze their histopathological features and their relationship with clinical features of the systemic disease. Patients with systemic sarcoidosis with predominantly subcutaneous sarcoid granulomas diagnosed between 1980 and 2016 in Bellvitge University Hospital were enrolled. We also analyzed patients with clinically and histopathologically identical lesions in whom a diagnosis of systemic sarcoidosis could not be made during follow-up. Twenty-eight patients with systemic sarcoidosis presented specific subcutaneous lesions (23 women and 5 men, mean age 55.64 SD 12.26 years). Dermal involvement was observed in 10 cases, always discrete and limited to deep reticular dermis. The distribution of the granulomatous infiltrate was lobular in 7 cases and lobular and septal in 21. Fibrosis was observed in 21 cases. There were no significant differences in persistence of lesions or persistence of systemic disease activity when comparing patients with and without fibrosis. In conclusion, fibrosis is a frequent finding in subcutaneous sarcoidosis, and although it may be intense, it is not associated with pulmonary fibrosis or with >2 years of persistence of systemic sarcoidosis activity.

644 Papillary and reticular fibroblasts generate specific microenvironments in vitro that impact their angiogenic profile

Human dermis is divided between the superficial papillary dermis and the deeper reticular dermis that show distinct extracellular matrix (ECM) and vasculature. Papillary and reticular fibroblasts have distinct phenotype and gene signature but the contribution of each subtype of fibroblasts in the generation of specific ECM and vasculature is poorly documented. This study aimed to determine if papillary and reticular fibroblasts generate specific microenvironments in vitro when cultivated as cell sheet and evaluate their impact on angiogenesis. RNAseq transcriptomic analysis of papillary and reticular cell sheets revealed that genes related to ECM and angiogenesis were the most regulated in both subtypes. Papillary and reticular fibroblasts showed specific matrisomes and we identified biological functions suggesting the deposition of distinct ECM. We then verified differences in ECM composition and ultrastructure at the protein level. We also identified angiogenesis gene signature with an enrichment in pro-angiogenic genes in the papillary fibroblasts. In agreement, the conditioned medium from these fibroblasts has a higher angiogenic potential compared to the reticular fibroblasts in 3D. Moreover, when cultivated with endothelial cells, papillary microenvironment induced the formation of a denser network of thinner capillaries compared to the reticular one, thus reproducing some features of dermis vasculature. These results indicate that papillary and reticular fibroblasts generate specific microenvironments when cultivated as cell sheets that differentially impact angiogenesis. This indicates that dermal fibroblast heterogeneity should be taken into consideration for tissue engineering and regenerative medicine applications.

Automatic motion correction for in vivo human skin optical coherence tomography angiography through combined rigid and nonrigid registration.

When using optical coherence tomography angiography (OCTA), the development of artifacts due to involuntary movements can severely compromise the visualization and subsequent quantitation of tissue microvasculatures. To correct such an occurrence, we propose a motion compensation method to eliminate artifacts from human skin OCTA by means of step-by-step rigid affine registration, rigid subpixel registration, and nonrigid B-spline registration. To accommodate this remedial process, OCTA is conducted using two matching all-depth volume scans. Affine transformation is first performed on the large vessels of the deep reticular dermis, and then the resulting affine parameters are applied to all-depth vasculatures with a further subpixel registration to refine the alignment between superficial smaller vessels. Finally, the coregistration of both volumes is carried out to result in the final artifact-free composite image via an algorithm based upon cubic B-spline free-form deformation. We demonstrate that the proposed method can provide a considerable improvement to the final en face OCTA images with substantial artifact removal. In addition, the correlation coefficients and peak signal-to-noise ratios of the corrected images are evaluated and compared with those of the original images, further validating the effectiveness of the proposed method. We expect that the proposed method can be useful in improving qualitative and quantitative assessment of the OCTA images of scanned tissue beds.

Microfocused Ultrasound for Facial Photorejuvenation: A Review.

Microfocused ultrasound is a unique technology to treat skin laxity of the brow, lower face, and the rhytides of the décolletage. Over the past several years, the efficacy and safety of this device has been well documented and its adoption widespread. By delivering focused acoustic energy, which is converted to heat, this device creates predictable and reproducible microcoagulative zones that initiate a concentrated inflammatory wound response. By targeting the deep reticular dermis and superficial muscle and fascial planes, such as the superficial musculoaponeurotic system, platysma, and pectoralis muscle fascia, this nonablative technology increases neocollagenesis and neoelastogenesis in a novel fashion, while avoiding many of the complications related to epidermal heating observed in several other nonablative devices. Although the results are not equivalent to those of a rhytidectomy, microfocused ultrasound provides an excellent noninvasive means to achieve a regenerative effect on the face, neck, and décolletage when performed in the appropriate patient population.

Noninvasive skin tightening: focus on new ultrasound techniques.

Microfocused ultrasound (MFU) has been recently developed to meet the ever-growing public demand for achieving significant, noninvasive skin lifting and tightening. MFU can be focused on subcutaneous tissue where the temperature briefly reaches greater than 60°C, producing small (<1 mm3) thermal coagulation points to a depth of up to 5 mm within the mid-to-deep reticular layer of the dermis and subdermis. The intervening papillary dermal and epidermal layers of skin remain unaffected. The application of heat at these discrete thermal coagulation points causes collagen fibers in the facial planes such as the superficial musculoaponeurotic system and platysma, as well as the deep reticular dermis, to become denatured, contracting and stimulating de novo collagen. A commercially available device combines MFU with high-resolution ultrasound imaging (MFU-V), which enables visualization of tissue planes to a depth of 8 mm and allows the user to see where the MFU energy will be applied (Ultherapy®; Ulthera Inc., Mesa, AZ, USA). Using different transducers, MFU-V treatment can be customized to meet the unique physical characteristics of each patient by adjusting energy and focal depth of the emitted ultrasound. By targeting the facial superficial musculoaponeurotic system, noninvasive tightening and lifting of sagging facial and neck skin and improvements in the appearance of wrinkles can be achieved. MFU-V can also improve lines and wrinkles of the décolleté. Treatment protocols for the use of MFU-V continue to be refined, and its use in combination with other rejuvenation techniques has been demonstrated. Brief discomfort that often occurs during treatment can be minimized with oral nonsteroidal anti-inflammatory drugs. Other treatment-related adverse events include transient erythema, edema, and occasional bruising. MFU-V is best suited for patients with mild-to-moderate skin and soft tissue laxity. For older patients with severe skin laxity and marked platysmal banding, surgical treatment should be considered.

Basaloid follicular hamartoma on the upper eyelid.

Basaloid follicular hamartoma on the upper eyelid.

Abstract B11: Mouse models of melanoma driven by oncogenic NRAS

Abstract Melanoma is the most deadly form of skin cancer and is a disease that is rising in incidence. Approximately 20% of all melanomas harbor activating mutations in NRAS. We previous used inducible-conditional approaches to express oncogenic NRAS (NRASG12D) at physiological levels in mouse melanocytes. When expressed in adult mouse melanocytes, NRASG12D induced skin darkening and blue nevus-like lesions but did not induce cutaneous melanoma. When expressed during embryogenesis, NRASG12D induced congenital nevi and leptomeningeal melanocytosis that replicated the cardinal features of human neurocutaneous melanosis. To extend these studies, we have examined how ERK signal strength affects NRASG12D-driven melanomagenesis. We previously demonstrated that kinase-dead BRAF drives paradoxical hyper-activation of ERK downstream of oncogenic RAS, so to investigate how ERK signal strength affects RAS-driven melanomagenesis, we expressed NRASG12D and kinase-dead BRAF (BRAFD594A) in adult mouse melanocytes. BRAFD594A did not induce any skin lesions. In accordance with our previous study, NRASG12D induced paucicellular nevi composed of pigmented dendritic melanocytes in the papillary and superficial reticular dermis. These lesions resembled nevus of Ota, but none of the mice developed melanoma. When BRAFD594A and NRASG12D were co-expressed, we observed the paucicellular nevi seen in NRASG12D mice, but additionally, we observed a proliferation of nevi in the deep reticular dermis, the hypodermis and enveloping the cutaneous adnexae. The cells in these lesions were heavily pigmented epitheliod or ovoid melanocytes and the lesions were reminiscent of dermal melanocytosis with scattered foci of blue nevi. More importantly, these mice developed melanoma that presented with two distinct histological types. The majority of the tumours presented as hypo-pigmented lesions that extended from the upper dermis into the subcutaneous layers, leaving a narrow or absent grenz zone and frequent focal ulceration. They were amelanotic and the predominant cells were undifferentiated atypical spindle melanocytes. The tumours replaced the normal architecture of the upper dermis, invading the adjacent and subcutaneous structures, and occasionally presented nevi remnants at their poorly defined borders. Less common, the tumours were hyper-pigmented lesions that arose in the deep reticular dermis, leaving a wide grenz zone and only occasionally ulcerating the epidermis. The tumour cells were predominantly heavily pigmented, pleomorphic epithelioid melanocytes, abutting into the deeper layers of the subcutis and the lesions resembled animal-type melanoma in humans. Thus, we show that ERK signal strength is critical for NRAS-driven melanomagenesis and this pathway drives different types of lesion that resemble human nevi and melanoma. Citation Format: Malin Pedersen, Amaya Viros, Richard Marais. Mouse models of melanoma driven by oncogenic NRAS. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B11. doi: 10.1158/1557-3125.RASONC14-B11

Dermal Spindle Cell Adenolipoma

Dermal Spindle Cell Adenolipoma

Nevus anelasticus: how should such lesions be classified?

Nevus anelasticus represents a rare entity that is most commonly classified as a connective tissue nevus. It typically presents before 20 years of age with asymmetrically distributed white-to-skin-toned or pink-to-red papules or plaques on the trunk and upper extremities. The lesion is defined histopathologically by the absence or degeneration of elastic fibers in the dermis. We report the case of a healthy 17-year-old female who presented with an asymptomatic slowly progressive plaque on the right inferior areola. Histopathologic examination showed the absence of elastic fibers in the papillary and upper reticular dermis and fragmented elastic tissue fibers in the deep reticular dermis. Although there is ongoing controversy regarding the nosology of this uncommon disorder, we propose that it is a distinct entity based on its histopathologic and clinical features.

Spectrum of features of Gronblad-Stradberg Syndrome

Pseudoxanthoma elasticum (PXE) with ocular and cutaneous features, also known as Grönblad-Strandberg syndrome, is a rare inherited disorder associated with mutations in the ABCC6 gene. PXE most commonly involves the elastic fibers of the mid and deep reticular dermis of skin, the Bruch membrane of the eye, and the blood vessels. Almost all patients with PXE have ocular involvement; with characteristic angioid streaks being seen in 85 % of the patients.The streaks represent cracks and fissures in the calcified Bruch’s membrane. This ocular change is generally bilateral and is often noted several years after the onset of cutaneous lesions. Prime cause of vision loss is development of macular choroidal neovascularisation (CNV). Patients with PXE typically have a normal life span, with mortality and morbidity largely due to extracutaneous manifestations like central vision loss, gastrointestinal haemorrhage and cardiovascular manifestations, such as angina and hypertension in later stages of the disease spectrum. Authors describe a classic case with typical ocular manifestations of angioid streaks and fine-yellow drusen like pigment irregularities at macula along with distinctive yellow plaques in the flexural areas of the body; posterolateral area of neck, antecubital fossa of arms, chest and thighs. Skin biopsy was done which confirmed the diagnosis

Desmoplastic melanoma associated with an intraepidermal lentiginous lesion: case report and literature review

Desmoplastic melanoma tends to present as firm, amelanotic papules. Microscopically, it reveals a proliferation of fusiform cells in the dermis and variable collagen deposition, as well as intraepidermal melanocytic proliferation of lentiginous type in most cases. Biopsy in a 61-year-old white male patient, who had received a diagnosis of lentigo maligna on his face 10 years before, revealed a proliferation of dermal pigmented spindle cells and collagen deposition, reaching the deep reticular dermis, with a lentiginous component. Immunohistochemistry with S-100, Melan-A and WT1 showed positivity, but it was weak with HMB45. Desmoplastic melanoma associated with lentigo maligna was diagnosed. Several authors discuss whether desmoplastic melanoma represents a progression from the lentiginous component or arises "de novo". Desmoplastic melanoma represents a minority of cases of primary cutaneous melanoma (less than 4%). Identification of lentigo maligna indicates that desmoplastic melanoma should be carefully investigated.