Netherton syndrome in a Bulgarian patient : Presentation of a case and an update of therapeutic options.

Comel-Netherton syndrome, or Netherton syndrome (NS), is a rare chronic genetic skin condition affecting the daily life of patients, which often results in poorly developed social skills and anxiety. Genetic predisposition plays a key role alongside the clinical findings, and clinicians must be aware of it as it can mimic other well-known skin conditions. Diagnosis is challenging both clinically and histologically. Clinically, it can mimic a severe form of atopic dermatitis, psoriasiform dermatitis overlapping with atopic dermatitis, or erythrokeratodermia variabilis. The difficulties in making histological diagnosis are similar, and it is often necessary to take several biopsies in order to clarify the diagnosis. Although retinoids are used for both psoriasis, erythrokeratodermia variabilis, and other congenital forms of keratodermia, the recommended treatment doses are different. This often results in poor treatment outcome. We present a 16-year-old patient previously diagnosed as erythrokeratodermia variabilis and treated with little to no improvement. Systemic therapy with acitretin 10 mg daily, local pimecrolimus 1%, emollients, and bilastine 20 mg once daily was initiated. Due to the limited application of retinoids and the difficulties in achieving permanent remission, modern medicine is faced with the challenge of seeking innovative therapeutic solutions. New hopes are placed on targeted or anti-cytokine therapy, based on inhibiting the inflammatory component of the disease. This article is mainly focused on innovative therapeutic options, including modern medications such as dupilumab, infliximab, secukinumab, anakinra, omalizumab, and others.

Giant cell epulis.

Giant cell epulis (peripheral giant cell granuloma) typically appears as a reactive benign lesion in the oral cavity in areas following local irritation or chronic trauma. Here we describe the case of a 45-year-old male patient who presented with the chief complaint of a large gingival mass in the anterolateral maxilla. There had been progressive growth within the past few months, with increased painless discomfort during mastication. The patient also reported bleeding during interdental cleaning. A full physical work-up led to the suspicion of giant cell epulis alongside other differentials including mucosal hemangioma and squamous cell carcinoma, with unremarkable laboratory values. Imaging including computed tomography showed signs of previous insertion of metal implants on either side of the lesion alongside mucosal hyperplasia. A confirmatory biopsy was taken and showed multiple giant cells on a reactive bed of stroma, in line with the diagnosis of giant cell epulis. Oral inflammatory conditions such as giant cell epulis have greater chances of local recurrence and, therefore, careful investigation with timely and accurate diagnosis is imperative for appropriate early treatment. Complete surgical excision should then be employed to prevent relapses, as incomplete removal can lead to further recurrence. Identification and eradication of potential sources of irritation should also be considered when treating the patient, to avoid further recurrence.

Advanced squamous cell carcinoma with massive cranial invasion: walking around without a forehead.

Squamous cell carcinomas with widespread invasion of the skull, meninges and brain parenchyma are extremely rare. Herein, we present an 86-year-old man with an 18-year history of sunburn who developed a large osteodestructive SCC that invaded through the frontal bone, frontal sinuses, and the dura mater. No neurological signs or symptoms or distant metastasis were noted. Such cases arise through patient neglect or lack of access to care and pose many challenges as lack of symptoms tend to deceive patients from seeking medical advice. Urgent aggressive treatment by a multidisciplinary team is paramount to achieving a successful outcome.

Preputial melanoma.

BACKGROUND: Melanomas of the glans penis, prepuce, and the corpus of the penis account for less than 1% of all melanoma cases. Due to this rarity, there is currently no standard treatment approach. CASE DESCRIPTION: We present the case of a 59-year-old patient with tumorous formations in the prepuce area. Histology was lacking at presentation. Medical history contained excision of a single formation with the character of a viral wart in the same area 1 year previously, with electrodesiccation for relapse a few months later. Due to the appearance of new bumps, the patient presented to the Onkoderma polyclinic. Dermatological examination revealed two nodular tumor formations: one with an erosive surface in the area of the prepuce and one subcutaneous lesion in the area of the right cavernous body. Differential diagnosis included Merkel carcinoma, dermatofibrosarcoma protuberans, anaplastic T/B cell lymphoma, and achromatic melanoma. Histology showed epithelioid cell infiltration and immunohistochemistry was positive for S100 protein, HMB 45, and melan A. Achromatic preputial malignant melanoma was diagnosed. The subcutaneous formation in the area of the cavernous body was defined as an in-transit metastasis. Penectomy under spinal anesthesia was planned. CONCLUSION: The prognosis for penile melanoma patients is currently poor, probably because of delays in diagnosis. Histopathologic evaluation after excision should be standard to prevent possible severe consequences such as penectomy and partial penile amputation.

Granulomatous slack skin mycosis fungoides developing simultaneously with sarcoid-like lesions in a patient with repeated anabolic injections in the past?

We present a 32-year-old man with successful treatment and remission of mycosis fungoides of both axillae in 2016 after PUVA therapy and systemic and local administration of corticosteroids. Subsequently, in 2017, the patient also achieved remission of a T-cell CD 30 positive, ALK-1 negative large-cell lymphoma of a retroperitoneal and inguinal lymph node after chemotherapy and radiotherapy. One year later, in 2018, the patient presented to our clinic with progression of skin lesions in both axillary areas and the appearance of а tumor in the right gluteal region.Dermatological examination showed livid-to-erythematous, partly sclerotic plaques in the right inguinal area, cutis laxa-like plaque formations in the right axillary region with similar but less-developed changes in the left axillary fold, a solitary subcutaneous tumor formation affecting the entire right gluteal region, and enlarged, palpable lymph nodes in the right para-axillary area. Biopsies were obtained from an axillary lesion and the surgically removed axillary lymph nodes, and histological examination revealed changes of granulomatous slack skin in the axilla and reactive inflammatory changes in the lymph nodes. Histology of gluteal tissue showed a "foreign body" type of reaction with sarcoid-like features, where the patient in the past have been injected with anabolic and steroidal drugs. Herein we describe a patient with simultaneous occurrence of granulomatous slack skin type mycosis fungoides and a sarcoid-like reaction. The question remains open whether this represents the so-called sarcoidosis-lymphoma syndrome or, more likely, granulomatous slack skin MF associated with a sarcoid-like reaction of "foreign body" type. The possibility that disturbance of tissue homeostasis by incorporation of certain adjuvants within injections (for example) in the past might have been an inducer of cutaneous T cell lymphoma and sarcoidosis/sarcoid like lesions seems reasonable but also speculative.

A novel surgical margin (1 cm) might be from benefit for patients with dysplastic nevi, thin melanomas, and melanoma in situ: Analysis based on clinical cases.

Malignant melanoma is an oncologic disease, whose current management among others includes surgical and immunological therapy. According to the current recommendations of the American Joint Committee on Cancer, the surgical excision of the primary tumor should be performed in two operative sessions, which has several consequences. The following paper will present and discuss six cases of pigmented lesions and the advantages of the one-step melanoma surgery in their management.

Tumorous formation of the forehead.

T­cell non-Hodgkin's lymphoma (NHL) represents approximately 10% to 15% of all lymphomas in Western countries. We present the case of a 16-year-old girl with nodular erosive tumor formation on the forehead within the previous 3-4 months and clinical evidence of cervical and submandibular lymphadenopathy in parallel. Tuberculosis verrucosa cutis, lupus vulgaris, cutaneous leishmaniasis, pyoderma faciale, sporotrichosis, infected insect bite, B­cell lymphoma, and atypical acneiform eruption were considered in the differential diagnosis. The patient has undergone therapy with oral ciprofloxacin (2â€¯× 250 mg/d) for 10 days and oral amoxicillin/clavulanic acid (2â€¯× 1 g/d) for 7-8 days, followed by oral clindamycin (2â€¯× 300 mg/d) and oral rifampicin (2â€¯× 300mg/d) for 4 weeks-all without any improvement. Unfortunately, disease progression was observed. Histologic examination revealed evidence of peripheral T­cell non-Hodgkin's lymphoma, and the subsequent immunohistochemical study confirmed the diagnosis, showing positive CD3 and CD4 expression and negative CD8, CD20, CD30, CD43, and ALK1 expression. Based on CT, lymph node involvement was found above and below the diaphragm, such that T­cell lymphoma stage 4E was concluded. CHOEP chemotherapy treatment was initiated, with a favorable clinical outcome after the first cycle.

Biofibre® artificial hair implant: Retrospective study on 1,518 patients with alopecia and present role in hair surgery.

To treat alopecia, there are many surgical and nonsurgical treatments available nowadays. In the surgical one, the Biofibre® hair implantation system represents an important innovation with artificial hair with special physical, chemical, and mechanical features and the new Biofibre® Automatic device. Implant on 1,518 patients has been reported in this study where the Biofibre® hair implant technique is performed on men and women with varying degrees of baldness and for the treatment of various causes of alopecia such as androgenetic alopecia, burns, and scars. According to our experience, this technique gives immediate and visible results without scarring or hospitalization and the aesthetic results are very encouraging for both male and female patients with a rapid recovery of self-esteem and psychological well-being.

Primavera: A new therapeutical approach to vulvo-vaginal atrophy.

Vulvovaginal atrophy is a condition that affects women, although it is mainly associated with the onset of menopause mainly due to hormonal changes vulvovaginal laxity and mucosal atrophy can also affect women at different life stages such as after pregnancy or for cancer patients who have undergone chemo or endocrine therapy. This condition negatively influence quality of life, sexual desire, and self-confidence. Many therapies have been considered mainly with inconclusive or transient results in terms of benefit factor. Recently, a new non-invasive product, containing hyaluronic acid, oligopeptides, and antioxidants was introduced to the market. Its name is "Primavera," by Renaissance, Italy. The aim of this product is to allow a vulvo-vaginal biostimulation and considered simple, safe, and satisfactory.

Interdigital melanoma simultaneously affecting two neighboring interdigital spaces : First description in the medical literature.

BACKGROUND: Interdigital melanoma, as a subtype of acral lentiginous melanoma, is relatively uncommon in the Caucasian population. It frequently goes unrecognized for a prolonged period of time prior to diagnosis, due to its asymptomatic nature and variable clinical appearance. METHODS: We report the case of a 67-year-old Caucasian woman who presented with interdigital malignant melanoma affecting two neighboring interdigital spaces. It had evolved over a period of more than 15 years and had been initially misdiagnosed as tinea pedis due to the macerated appearance of the lesion and a positive mycologic examination. RESULTS: We highlight the striking involvement of two adjacent interdigital spaces and the neighboring area of the sole of the foot by the tumor. The melanoma was staged as IIIC, with pathologic grading T4bN2bM CONCLUSIONS: The involvement of two adjacent interdigital spaces is unusual and, to our knowledge, has not been previously highlighted in the medical literature. It may be explained, in part, by the longstanding nature of the lesion in our patient.

Auricular pseudocysts.

Auricular pseudocysts are uncommon benign lesions of the pinna. The etiology is not well understood but repeated trauma is considered as a possible trigger. Exact diagnosis is important to avoid overtreatment with disfigurement. Various surgical approaches can be used in accordance to the stage of the lesion. Minor invasive procedures provide good results with low recurrence rates.

Pyoderma gangrenosum-a novel approach?

Pyoderma gangrenosum (PG) represents a rare skin disorder, with several clinical variants and still not fully understood ethiopathogenesis. Often associated with inflammatory or neoplastic disease, PG is nowadays considered an inflammatory neutrophilic disease with common underlying morbidity. Modern treatment options are oriented towards key mechanisms underlying the pathogenesis of the disease, namely inflammatory mediators, and seem to be the most effective treatment currently available. Although promising, the results are not invariable and these treatments are sometimes surrounded by controversy, as recent studies have reported cases that are refractory to therapy with biological agents. It is possible that refractoriness to the use of biological agents as monotherapy stems from the fact that a single agent is not able to affect the entire inflammatory cascade, or to simultaneously influence all of its levels. Based on the pathogenesis of inflammation, we can suggest that an ideal targeted therapy should be able to induce the following changes: 1) reduction of the secretion of interleukin (IL)-1a/b from the inflammasome with subsequent blocking of its biological effect (by therapy with IL-1 receptor antagonists); 2) blocking of the activation of the secreted procytokines in their active form (by therapy with caspase-1 inhibitors; 3) blocking of the effect of the already released active cytokines (by therapy with tumour necrosis factor alpha, TNF-α, inhibitors); 4) blocking of the effector action of the cytokines on the target intracellular molecules (by therapy with kinase inhibitors). The specific therapy should aim to attack more than one link in the inflammatory cascade, in order to achieve maximum therapeutic effectiveness. Most surely, this could be achieved with combined therapy with different groups of biological agents (for example a combined therapy with IL-1 receptor antagonist and a TNF-α inhibitor). Currently, no data in the literature exist to support this statement, and there are no safety data relating to such approaches. We focus this review on the novel etiopathogenetic concepts of PG and the future therapeutic approaches based on blocking different levels of the inflammatory cascade, which seems to be the most promising weapon in the target-oriented treatment options.

Cutaneous and visceral leishmaniasis during anti-TNFα therapy.

The long-term use of novel antipsoriatic systemic biotechnological drugs may increase susceptibility to opportunistic infections. Several cases of visceral leishmaniasis have been reported in immunosuppressed individuals, including those who have been treated with tumour necrosis factor alpha (TNFα) blocking agents. Simultaneous occurrence of cutaneous and visceral involvement has been more rarely recorded in the medical literature. Herein, we describe a case of mucosal leishmaniasis occurring in a farmer living in an endemic region, who was treated with golimumab because of psoriatic arthritis. This highlights the importance of recognizing cutaneous lesions as a first indicator of possible underlying kala-azar disease.

Multiple nonsyndromic acquired basal cell carcinomas : Uncommon clinical presentation in a Bulgarian patient.

Basal cell carcinoma is the most frequent cutaneous neoplasm, with slowly progressive nature and locally invasive behavior. Despite the low metastatic potential, local tissue destruction and disfigurement caused by the tumor can be large if not eradicated in time by early diagnosis and treatment. Both genetic predisposition and exposure to environmental risks are involved in the pathogenesis of the malignant transformation in BCC. The total number of nonmelanocytic skin cancers is a risk factor for recurrence of previous tumor, on the one hand, as well as for the formation of new ones, on the other. It is still unclear what environmental and genetic factors contribute to the development of multiple nonsyndromic BCCs. We present a man with multiple sporadic, nonsyndromic BCCs, with a history of even more lesions, removed earlier, as we discuss the potential triggering risk factors and pathogenic mechanisms of malignant transformation and the further appropriate therapeutic options. The early detection and eradication of these tumors are of importance for treatment effectiveness and quality of life because although rarely metastatic, BCCs could have an aggressive course and behavior which can lead to severe disfiguration and destruction.

Undermining plastic surgery as a possible option for treating basal cell carcinoma of the forehead.

Basal cell carcinoma (BCC) is the most common cutaneous cancer. Although most cases can be cured with simple surgical procedures and are associated with a good prognosis, a minority of BCCs may pose significant therapeutic challenges. This occurs mostly in cases of so-called advanced BCC, which a loosely defined term that encompasses locally advanced lesions and tumors with metastatic spread. Treatment of these cases is often complex and sometimes may need combinations of therapeutic modalities, including surgery, radiotherapy and/or targeted therapy directed towards sonic hedgehog (SHH) signaling pathways, such as vismodegib. We herein present the case of a 74-year-old man presenting with a large basal cell of the forehead evolving for more than 7 years. The patient underwent excision of the lesion with clear surgical margins. Reconstruction of the defect was performed after extensive undermining of the skin allowing subsequent direct closure with a simple suture, which resulted in an acceptable cosmetic outcome. We discuss the potential advantages, disadvantages, and applicability of this relatively simple surgical maneuver in the reconstruction of defects resulting from excision of considerably large cutaneous tumors.

Trombiculiasis: not only a matter of animals!

Trombiculiasis represents a striking emerging infestation in humans. In fact, modified lifestyles and easy and quick traveling around the globe, together with the altered ecology and habits of the parasite Neotrombicula autumnalis, make this original epizoonosis an extraordinary example of synanthropic dermatosis. We present an additional clinical image of this unusual parasite transmission from animals to humans occurring in a trekker in Calabria, Italy.

Disseminated superficial actinic porokeratosis (DSAP): significant improvement after local administration of calcipotriol/betamethasone gel?

Porokeratosis is defined as a disorder of keratinization characterized by one or more atrophic patches surrounded by a clinically and histologically distinctive hyperkeratotic ridgelike border called the cornoid lamella. Lesions are most commonly located on the sun-exposed sides of trunk and extremities, while exclusive facial involvement has been also reported. Despite that the exact risk of cutaneous malignancy developing in porokeratosis is unknown, it is confirmed by series of case reports, including squamous cell carcinoma, basal cell carcinoma and even melanoma. Although no definite cure exists, a number of treatment modalities, from topical medications to laser and light devices, have been reported with variable success. Although promising, reports of disseminated superficial actinic porokeratosis treated with vitamin D3 analogs are rare. No satisfactory enough effect is obtained also with calcipotriol monotherapy.We report a case of disseminated superficial actinic porokeratosis in a 80-year-old female patient, successfully treated with combination of topical calcipotriol/betamethasone gel. A significant improvement was noticed after 3 weeks; almost full resolution of the clinical symptoms without appearance of fresh lesions was achieved in the second month. To the best of our knowledge, this is the first report of successful treatment with full resolution in a short interval, by simultaneous application of vitamin D3 analog (calcipotriol) and corticosteroid (betamethasone), combined in a one commercial product as a gel for treatment of keratinocyte proliferation's disorder such as psoriasis vulgaris. This promising new entity seems to be more effective, because of the simultaneous synergetic effects of the substations, namely the normalization of the proliferation of the keratinocytes by calcipotriol on one hand, and the reducing of the inflammation by the corticosteroid on another. Sun protection stays always mandatory, as well as the regular clinical observation, regarding the risk of malignant transformation.

Terra firma-forme dermatosis.

Terra firma-forme dermatosis (TFFD) belongs to the group of "dirty dermatoses" and represents a not well-known and surely underestimated vexing skin condition. Firstly described by Duncan, Tschen and Knox in 1987, it accounts for a few case series in the literature and has a still undefined aetiology. The authors present an additional report of TFFD, occurring in a young Caucasian girl, and briefly review the current medical literature on the topic.

Rare association of cystic squamous cell carcinoma and small lymphocytic B cell lymphoma: successful surgical approach.

Non-melanoma skin cancer is the most common type of cutaneous neoplasm worldwide. While basal cell carcinoma is the most common tumor, squamous cell carcinoma (SCC) causes higher morbidity and has a risk of metastatic spread, depending on immune status, tumor size, and desmoplastic growth. We reported the case of a 77 year old male patient with retroauricular tumor, which started growing 3 years ago and was excised, buth relapsed three times. The initial diagnosis was infundibular cyst. Delayed Mohs surgery was performed, as was an additional open lymph node biopsy of the patient's right groin, on the occasion of an indolent swelling of the same which developed within 3 months. The first histopathological report confirmed the diagnosis of a cystic squamous cell carcinoma. The histopathologic evaluation of the groin tumor revealed a small lymphocytic B cell lymphoma (BCL). The patient fulfilled the following criteria for high-risk SCC: tumor size ≥2 cm (or 1 cm on the head and 6 mm on the genitals, hands, and feet), tumor thickness ≥4 mm, recurrent tumor, rapid growth. Therefore, lymph node metastasis had to be considered. High-risk SCC has a propensity to metastasize. In cases of primary tumor, Mohs surgery is the most effective treatment, particularly in relapsing tumors. The combination of cystic SCC with a small-sized BCL is very rare. The differential diagnosis and treatment may be challenging. In high-risk SCC, lymph node enlargement warrants histologic evaluation. However, not all suspicious lymph node lesions corroborate as metastatic.