Granulomatosis with polyangiitis (GPA) is a rare ANCA-associated small-vessel vasculitis that predominantly affects the respiratory tract and kidneys, while cutaneous manifestations occur less frequently. Opportunistic fungal infections complicating GPA are uncommon, particularly involving rare filamentous basidiomycetes. We describe a 32-year-old male with a prolonged history of crusting rhinitis, tinnitus, and progressive nodular and ulcerative skin lesions on the trunk and extremities, accompanied by fever and lower limb edema. Laboratory evaluation revealed elevated inflammatory markers and positive c-ANCA (anti-PR3). Histopathology demonstrated granulomatous inflammation consistent with GPA. The clinical course was complicated by a secondary cutaneous infection caused by Hormographiella aspergillata, isolated from a skin lesion. Initial antifungal therapy with itraconazole was ineffective; subsequent treatment with voriconazole resulted in resolution of the fungal infection. The patient was then successfully treated with systemic immunosuppressive therapy, achieving long-term remission. To our knowledge, this is the first reported case of GPA complicated by a cutaneous infection with H. aspergillata. This case highlights the diagnostic challenges of GPA with atypical skin manifestations and underscores the importance of microbiological evaluation of skin lesions prior to initiating aggressive immunosuppressive therapy. KEYWORDS: granulomatosis with polyangiitis; ANCA-associated vasculitis; Hormographiella aspergillata; opportunistic fungal infection Granulomatosis with polyangiitis (GPA), formerly Wegener's granulomatosis, is a necrotizing granulomatous vasculitis affecting small to medium-sized blood vessels and belonging to the group of ANCA-associated vasculitides (AAV) (1). The disease is characterized by granulomatous inflammation, necrotizing vasculitis, and the presence of antineutrophil cytoplasmic antibodies, most commonly proteinase-3 ANCA (PR3-ANCA) (2). GPA may involve virtually any organ system, with predominant involvement of the upper and lower respiratory tract and kidneys (3). Cutaneous manifestations are reported in approximately 30-50% of patients and are usually associated with systemic disease activity (4). Opportunistic infections may complicate the course of GPA, particularly in the context of delayed diagnosis or immunosuppressive therapy. Infections caused by rare filamentous fungi such as Hormographiella (H) aspergillata are exceptionally rare and have predominantly been reported in immunocompromised patients with hematological malignancies (5, 6). A 32-year-old male was admitted with multiple painful ulcerations and nodules on the trunk and extremities, accompanied by high fever and marked bilateral lower limb edema. Four months before admission, nodular lesions on the left auricle and right nipple regressed spontaneously after purulent discharge. Six weeks prior to referral, painless nodules on the back and right upper arm were surgically incised and treated with antibiotics, followed by clinical deterioration with fever, progressive ulcerations, and painful swelling of the feet and ankles (figures 1a and !b). The patient had a two-year history of nasal obstruction, crusting rhinitis, and intermittent right-sided tinnitus. Rhinoscopy revealed mucosal thickening and septal perforation with crusts and synechiae. Dermatological examination showed deep ulcerations with yellow-brown crusts on the back, right upper arm, and left cheek (figures 1a and 1b). Laboratory evaluation demonstrated elevated inflammatory markers (ESR 76 mm/h, CRP 47.4 mg/L), hypoalbuminemia, and positive c-ANCA (anti-PR3). Initial microbiological cultures were sterile. Histopathology revealed granulomatous panniculitis with abscess formation. Fungal culture isolated H. aspergillata. Itraconazole therapy was ineffective; subsequent voriconazole treatment led to complete resolution of the cutaneous infection. Due to persistent systemic inflammation and c-ANCA positivity, the patient was treated with high-dose glucocorticoids and cyclophosphamide, which gradually led to completely remission of skin lesions (figure 2). Renal involvement developed during treatment, manifested as proteinuria. Long-term immunosuppressive therapy resulted in sustained remission with mild residual renal impairment. GPA is a rare multisystem autoimmune disease with heterogeneous clinical presentation, often leading to delayed diagnosis. Cutaneous involvement may be the initial manifestation and includes purpura, nodules, necrosis, and ulcerations, reflecting underlying vasculitis and granulomatous processes (2). In our patient, prominent skin lesions preceded the diagnosis by several months and contributed to diagnostic uncertainty. Opportunistic infections are a recognized complication in GPA, particularly following immunosuppression; however, fungal infections caused by filamentous basidiomycetes are exceedingly rare (5, 6). Hormographiella aspergillata, the anamorphic form of Coprinopsis cinerea, is an environmental fungus that has been implicated almost exclusively in invasive infections in patients with hematological malignancies, with reported mortality rates up to 70% (5, 6). To our knowledge, no previous case of GPA complicated by cutaneous infection with H. aspergillata has been reported. The present case underscores the importance of thorough microbiological evaluation of atypical or non-healing skin lesions in patients with suspected systemic vasculitis, particularly before initiation of intensive immunosuppressive therapy. Failure to recognize opportunistic infections may lead to significant morbidity and mortality. This case emphasizes the crucial role of dermatologists in the early recognition of systemic vasculitis presenting with skin manifestations. Comprehensive clinical, histological, and microbiological assessment is essential to establish the correct diagnosis and to identify rare infectious complications. Multidisciplinary management and careful monitoring are necessary to achieve long-term remission and to minimize treatment-related complications.
Dear editor, Haemangiomas are common benign vascular tumours usually detected on skin, mucosal surfaces, and soft tissues. In some extremely rare cases, haemangiomas can occur within a lymph node and as such are classified as primary benign vascular tumours of the lymph nodes, along with lymphangiomas, haemangioendotheliomas, and angiomyomatous hamartomas (1-2). A study reported that the overall prevalence of benign primary vascular intranodal tumours is only 0.3% (3). Even though intranodal haemangiomas are benign and usually asymptomatic, in clinical practice it is often challenging to differentiate them from primary malignant intranodal tumours or secondary malignancies. Herein, we describe a rare case of a femoral intranodal haemangioma in a melanoma high-risk patient, which was initially diagnosed as a melanoma metastasis. This appears to be the first reported instance of an intranodal haemangioma considered as a differential diagnosis of a melanoma metastasis. A 45-year-old female patient was admitted to our Clinic in June 2021 for a regular check-up after a melanoma excision on her left upper leg three years earlier. Histologically, it was a nodular melanoma of 6.22 millimetres Breslow thickness, Clark IV level, and 5 mitoses per square millimetre. Shortly after the primary excision and due to the unfavourable histopathological parameters, a preoperative positron emission tomography/computerized tomography (PET/CT) was done in which no pathological accumulation of radiopharmaceutical was observed. In histopathological findings of subsequently performed scar reexcision and left groin sentinel lymph node biopsy (SLNB), no tumour cells were detected. Since then, the patient had regular check-ups every few months in which all clinical, ultrasound, and laboratory findings were normal. A control PET/CT for this high-risk melanoma patient was done three years later, in June 2021. In comparison with the first PET/CT, a progression in size was observed in a hyperdense lymph node in left femoral region, diameter of 15 mm, now with increased accumulation of radiopharmaceutical (Figure 1). To exclude melanoma metastasis, an ultrasound of the left femoral region was done in which a well-defined, hyperechoic lesion with increased vascularity on colour Doppler was seen. As recommended by a radiologist and due to an unclear diagnosis, a excisional biopsy of the described femoral lymph node was conducted. Histopathological analysis revealed an oval, circumscribed vascular formation within most of the lymph node tissue (Figure 2a and 2b), predominantly composed of cavernous-like blood vessels and vascular spaces filled with erythrocytes and lined with thinned endothelium (Figure 2c and 2d). The lesion was sharply demarcated from the surrounding nodal tissue. No nuclear atypia or mitotic activity was observed. The described histopathological features led to a diagnosis of a primary intranodal haemangioma. At present, four years after the primary excision of melanoma and one year after the detection of intranodal haemangioma, the patient remains disease-free. Although lymph nodes frequently show extensive vascularity associated with many different infections and diseases, the verification of a primary vascular tumour in a lymph node is a very rare occurrence (6). Apart from Kaposi's sarcoma, only few examples of such intranodal vascular tumours have been reported, of which most of them were benign haemangiomas. Haemangiomas are ubiquitous tumours that can be found on skin, mucosa, and all internal organs, and are considered as the most common benign neoplasm of the liver. Histologically, there are 4 types of intranodal haemangiomas: capillary/cavernous, lobular, cellular, and epithelioid (1,6). Intranodal haemangiomas present as asymptomatic, solitary, palpable lymph nodes or as an incidental finding. They usually affect only one lymph node and rarely cause any functional impairment. In most of the previously published cases, intranodal haemangiomas have occurred within nodes of sites draining malignant tumours, i.e., after mastectomy following breast cancer diagnosis or salpingo-oophorectomy after ovarian cancer diagnosis (2,6,7). The treatment of primary lymph node haemangiomas includes surgical resection, which is considered curative (5,8,9). The prognosis is excellent, and the recurrence rate of these tumours has not been described (6,9). In our case, surgical extirpation was performed for the purpose of excluding metastatic disease. This appears to be the first reported instance of an intranodal haemangioma considered as a differential diagnosis of a melanoma metastasis. A causative relationship between melanoma and intranodal haemangioma has not been established but it is believed that these two lesions occur independently of each other. The identification of intranodal haemangiomas is important to avoid misdiagnosis as malignant vascular tumours, such as Kaposi's sarcoma or angiosarcoma, which are more common in lymph nodes. Since Kaposi's sarcoma can initially occur in lymph nodes, without the cutaneous involvement, this distinction requires special emphasis. Moreover, intranodal haemangiomas can also be suspected as secondary malignancies, especially in patients with high-risk malignant tumours, just like our patient was, so it is of great importance to think about intranodal haemangioma as a rare differential diagnosis of a lymphogenic metastasis.
Dear Editor, Genodermatoses are usually diagnosed in early childhood but diagnosis may be delayed in rare cases. Schöpf-Schulz-Passarge syndrome (SSPS) first described in 1971 is a rare type of autosomal recessive ectodermal dysplasia characterized by palmoplantar keratoderma, periocular and eyelid apocrine hidrocystomas, hypodontia, hypotrichosis, and nail dystrophy (1). Fewer than 40 cases have been reported up to 2018 (2) and the number has slightly increased with subsequent case reports. We report here a 73-year-old male patient whose parents were third-degree cousins presented to dermatology clinic for symptomatic palmoplantar hyperkeratosis (Figs 1a-1b) with a 30-years history. Physical examination determining mild alopecia (Fig. 1c), dental loss (Fig. 1d), micronychia (Figs 1e-1f) in association with numerous cystic lesions suggested the diagnosis of SSPS. Remarkably numerous hidrocystomas localized to the eyelids, periocular area, cheeks, nose, forehead, ears, shoulders, supraclavicular and axillary region showed three distinct morphologies; milia-like yellowish (Fig. 2a), bluish dome-shaped (Figs 2a-2b, 2d) and translucent (Fig. 2c) papular lesions. The histopatological examination determining the diagnosis of apocrine hidrocystoma (Figs 2e-2f) was followed by genetic confirmation of SSPS. A homozygous c.391G>A (p.Ala131Thr) variant was identified in WNT10A by Clinical Exome Sequencing. According to American College of Medical Genetics and Genomics criteria (3), this variant was classified as pathogenic (PS4, PM1, PM2, PM5, PP3, PP5). Rarely reported findings of SSPS including facial dysmorphism, loss of body hair (Fig. 2d), localized hyperhidrosis (Fig. 1f), generalized hypohidrosis, and atrophic tongue (Fig. 1d) was also associated. However, other rare supporting features, such as eccrine syringofibroadenoma, rosacea-like facial erythema, hypoplastic areolae and nipple, and ocular involvement were not observed (4-7). The patient had also a basal cell carcinoma on the nose (Fig. 2c) which has been occasionaly reported in SSPS (4). Furthermore, a 9 × 9 cm soft, subcutaneous mass located on the midline of the lumbar region, clinically suggestive of a lipoma, was also noted. In our case, although dental loss was the earliest presenting feature, major manifestations such as periocular and eyelid apocrine hidrocystomas and palmoplantar keratoderma emerged initially after the 5th decade, leading to a delay in diagnosis. Whereas extraocular localizations of apocrine hidrocystoma is described in sporadic cases (8), it has not been highlighted in the context of SSPS. Our patient, however, exhibited numerous lesions in multiple additional sites including the nose, cheeks, forehead, external ears, upper trunk and axillae, broadening the recognized clinical distribution of this hallmark finding. A noteworthy finding in this patient was the concurrent presence of three morphologically distinct types of facial apocrine hidrocystomas. While a review of previously reported cases revealed that lesions with different morphologies can coexist in individual patients (2), this phenotypic diversity has rarely been explicitly highlighted in the literature. WNT10A mutations, inherited in an autosomal recessive manner, have been documented in both homozygous and compound heterozygous states (7, 9). These mutations can result in a wide phenotypic spectrum, ranging from isolated hypodontia and oligodontia to more complex ectodermal dysplasia syndromes such as odonto-onycho-dermal dysplasia (OODD) and SSPS (5, 6, 9). On the other hand some authors suggest that these two conditions may represent phenotypic variations of the same underlying genetic defect rather than distinct entities (10). While our patient exhibited overlapping features with OODD, including hypodontia, palmoplantar hyperkeratosis, hypotrichosis, and nail dystrophy, the presence of numerous apocrine hidrocystomas was distinctive for SSPS (5)D. In conclusion, SSPS can be recognized even decades after onset of the mild dermatological manifestations (2). Awareness of the rich clinical spectrum of apocrine hidrocystomas as they are not limited to eyelids or periocular area and present with papulonodules in different size and color may be crucial (5)D. Although a therapeutic option for SSPS still does not exist timely recognition may prevent unnecessary diagnostic and therapeutic interventions and enable appropriate genetic counseling of the family members.
Sweet's syndrome (acute febrile neutrophilic dermatosis) is an inflammatory condition characterized by the abrupt onset of erythematous, oedematous plaques or nodules and a dense neutrophilic dermal infiltrate. Although usually associated with fever and tender lesions on the face and upper extremities, its clinical spectrum is broad, and atypical presentations may pose diagnostic challenges. We report the case of a 50-year-old female patient who presented with an acute eruption of widespread, annular, erythematous, and oedematous plaques predominantly involving the trunk and extremities, accompanied by severe pruritus. The patient denied fever or other systemic symptoms. Laboratory investigations demonstrated marked leukocytosis with neutrophilia and elevated inflammatory markers. An extensive infectious, immunological, and malignancy workup was unremarkable. Histopathological examination revealed a dense neutrophilic dermal infiltrate with leukocytoclasia in the absence of true vasculitis, consistent with Sweet's syndrome. Direct immunofluorescence was negative. The patient reported a history of similar episodic eruptions over two decades, often temporally associated with respiratory infections. Systemic glucocorticoid therapy led to rapid clinical improvement and normalization of inflammatory parameters, with complete resolution at follow-up. This case highlights the clinical heterogeneity of Sweet's syndrome, demonstrating that prominent pruritus, truncal predominance, and afebrile presentation may occur. Recognition of atypical manifestations is essential to avoid misdiagnosis, particularly with urticarial or allergic disorders. Thorough evaluation for associated systemic disease and careful documentation of recurrent patterns remain crucial. Early histopathological confirmation and prompt initiation of appropriate therapy enable rapid disease control and favourable outcomes.
Folliculitis decalvans, typically observed in adult males, is rare in pediatric populations. This case report explores the diagnosis and management of a 12-year-old boy with this condition, marking a rare pediatric case in Greece. The patient, a 12-year-old boy of Greek descent, initially presented with symptoms of hair loss beginning at three years of age. Over the years, he developed alopecic patches on the scalp characterized by perifollicular erythema, hyperkeratosis, and tufted hair, accompanied by mild itching and discomfort The report discusses the diagnostic challenges (dermoscopy, histological examination), treatment strategies, and the patient's response to a multimodal treatment regimen.
Dear Editor, Tattooing is a popular decorative procedure worldwide1,2. Its prevalence in adults ranges from 20 to 30%1,3. However, Google Trends (GT) infodemiological data indicate that interest in tattoos began declining before the COVID-19 pandemic4. As trends may vary across regions, we aimed to determine whether a similar pattern occurred in Eastern Europe and the Balkans. We used the same method as published elsewhere for previous tattoo health-related research using GT2,4,5. GT is a useful website that provides data on the relative search volume (RSV) of queries and topics over time and across geographical areas (worldwide, country, city). It allows seasonal and long-term assessment of trends in public interest. We analyzed the data generated through GT, for the mean RSV on the topic "tattoo" for each Balkan country (Albania, Bulgaria, Greece, North Macedonia, and the nations of the former Yugoslavia: Bosnia and Herzegovina, Serbia, Croatia, Montenegro, and Kosovo) from January 1, 2004, to December 27, 2025. Results are displayed as a set of time series. The values are not the actual search counts but percentages relative to the total searches across the specified geography and time. The resulting numbers are then scaled from 0 to 100 based on the proportion to all searches on all topics. All data used in this study are publicly available, anonymous, and cannot be traced back to identifiable individuals. Every country displayed the similar seasonal search patterns as observed elsewhere2 with peaks during summer and dips during December (data not shown). Between 2004 and 2025, interest in tattoos has first increased gradually before reaching a peak around 2011-2019, depending on the country, followed then by a constant decrease (table 1). The phenomenon is notable in every Balkan country (Fig 1). Only Kosovo shows a mean increase in search. The prevalence of tattooing in the Balkan peninsula is globally unknown. Available studies are usually limited by strong bias of selection. A small Croatian study found that about 15% of surveyed patients reported having at least one tattoo6. About 19 % of adult Bulgarians reported having a tattoo in 20227. In Greece, a study among young Athenians aged 19-25 years-old, the prevalence was elevated however the study was most likely biased due to the recruitment procedure8. It is rather likely that the prevalence at least in urban areas in the Balkan mirrors results observed in Western or Northern Europe. However, it is interesting to discern that the same trend regarding a decrease in interest in tattoos can be observed both in Western and Eastern Europe. Kosovo appears as an outlier compared to its neighbors. The increase may be explained by the rapid expansion of the use of internet in the country9. Besides, a careful analysis of the overall trends in Kosovo shows rather a stabilization now (data not shown). As observed previously, the decrease began before COVID-194, indicating that the pandemic cannot be held responsible. This trend is corroborated by tattoo artists and industry observers who report a slowdown in demand, with appointment books no longer filling as quickly and income diversification becoming necessary. Rising inflation and living costs may reduce tattoos' priority for consumers. Additionally, established artists face increasing competition in an unregulated sector characterized by oversupply, low visibility for those not active on social media, and growth of low-cost alternatives (e.g., home-made tattoos and online equipment purchases). Media coverage of the potential carcinogenicity of tattoo inks, often sensationalized despite robust evidence10, may have further contributed. Study limitations include reliance on Google Trends, which is not a true epidemiological tool and only captures internet users, limiting population representativeness9. Acknowledging the limits of our study, the current loss of interest in tattoos seems widespread and across Europe.
Fast-growing ulcerations in the oral cavity are clinically challenging lesions with potentially different pathogenesis. Traumatic ulcerative granuloma with stromal eosinophilia represents a benign oral mucosa lesion with unclear pathogenesis, most commonly occurring on the tongue. The etiology of this uncommon disease remains to be elucidated, although several triggering factors are thought to be implicated in pathogenesis including trauma, viral or toxic agents. We report a case of a 42-year-old female patient with traumatic ulcerative granuloma with stromal eosinophilia involving the lateral aspect of the tongue, clinically assessed with the auxilium of dermatoscopy. Since clinical and dermatoscopic evaluation could not give a precise diagnosis, additional serological methods and a biopsy of the lesion were performed with pathohistological evaluation. This case report highlights the need for awareness amongst dermatologists for traumatic ulcerative granuloma with stromal eosinophilia of the tongue as a great clinical and dermatoscopical simulator.
A 30-year-old man with recent diagnosis of HIV-infection was seen in the hospital, because of a 1-month history of swollen lips, painful oral mucosa ulcers, cervical lymph nodes and skin lesions. The medical history showed a previous patient contact with 10 subjects, with positivity for Monkeypox virus in 8 subjects. A week later, he began with lesions on the genitals, managed with acyclovir, and subsequent development of manifestations in the mouth and skin, with dissemination to the entire body. He was admitted to our clinic for increased volume in penis and scrotum, and a disseminated dermatosis affecting all body segments, characterized by polymorphic lesions reflecting various stages; the condition presents as infiltrated plaques with a central eschar and two halos at the periphery: one pale and another erythematous, of varying sizes, accompanied by significant edema (Figure 1A). In the mouth there was lip edema, with the presence of multiple superficial round ulcers and vesicles, with a hemorrhagic center and a white-yellowish border, that coalesce forming circinate plaques, with serohematic crusts on the upper vermilion and hematic and meliceric crusts on the lower one, as well as pale mucosa (Figure 1B). Intraorally, painful large shallow ulcers, covered with fibrin and hemorrhagic areas, with rounded and irregular edges, affected both labial mucous membranes, the hard palate and gums, with gingival enlargement and necrosis of the interdental papillae (Figure 1C); the tongue showed partial atrophy of filiform papillae with some isolated punctiform ulcers. A presumptive diagnosis of Monkeypox infection was suggested. Biopsies on lower labial mucosa and plantar skin were performed. Analysis of blood test revealed: hemoglobin 10.8 (13.1 - 18.1) g/dL, iron 22 µg/dL (50 - 212), ferritin 2362 (23 - 336,2) ng/mL, leukocytes 10.8 (3.9 - 10.1)/mm3, aspartate aminotransferase 47.3 (13 - 39) U/L, albumin 2.4 (3.5 - 5.7) g/dL, CD4 count 121 (500-1500) cells/mm3 and HIV-viral load 312,000 (<20-75) copies/mL, starting antiretroviral therapy with bictegravir/emtricitabine/tenofovir alafenamide (biktarvy) and management with antibacterials and antivirals. The histopathological study of lesions was compatible with monkeypox infection and PCR test for the monkeypox virus confirmed the diagnosis (1,2). The patient had increased difficulty in swallowing, first with solids then with liquids; and, given the risk of airway obstruction due to oropharyngeal edema, a tracheostomy was performed. Disease progression was observed, with kidney damage and pulmonary dysfunction, and he died a month later. Mucocutaneous and other clinical features such as fever, chills, headache, muscular pains, backaches, and weariness, are some of the first symptoms of a Monkeypox infection.(2-5) A gradual maculopapular rash with lesion diameters ranging from 0.2-1 cm appears after the prodrome stage; initially on the face and neck, and moving to the legs with involvement of the palms and soles, spreading throughout the body.(2, 5) These last characteristics favored the initial diagnosis of a Monkeypox infection in our patient. Differential diagnosis should include other pox-like viruses, such as varicella, herpes zoster, measles, and arboviruses (Dengue, Zika and chikungunya). (2) This case represents a rare situation where the host rapidly developed progressive worsening of Monkeypox manifestations in HIV-infection.
Aquagenic keratoderma (AK) is a rare acquired and transient disorder of stil unknown etiology. This keratoderma is characterized by the appearance of whitish or translucent papules and folds on the skin of the palms and soles, after contact with water. It more commonly affects younger women, although men with this condition have also been reported. It is benign in nature but impacts the quality of life for those affected and causes discomfort when engaging in "water" sports. The term "watersport hands" has been proposed, although, as you will see in the text, this keratoderma already has many synonyms. We present a patient with aquagenic keratoderma. We conducted a detailed review of the literature on the etiology, pathogenesis, diagnosis and therapeutic modalities of this rare keratoderma. A healthy 22-year-old woman was examined due to the appearance of skin changes three minutes after contact with water. Initially, there were white, round lesions with a sense of discomfort, followed by folds on the fingertips. The skin changes last for about forty minutes, gradually resolving as the skin dries. Based on clinical examination before and after exposure to water, dermoscopic findings, and histopathological examination, the diagnosis of AK was established.
Melanoma accounts for less than 2% of all cancers worldwide but is responsible for 80% of skin cancer-related deaths. Among the various genetic alterations in melanoma, BRAF and NRAS mutations are the most common. While multiple studies have confirmed the involvement of BRAF in melanoma, its role as a prognostic marker remains disputed. However, the BRAF V600E mutation is clinically significant, as its presence determines eligibility for targeted therapy with BRAF inhibitors. This retrospective study aimed to correlate BRAF mutation status with the clinicopathological characteristics of primary skin melanoma, assess the impact of BRAF-mutated versus BRAF wild-type melanoma on disease progression and overall survival, and evaluate the influence of BRAF inhibitor therapy on survival outcomes. 152 melanoma patients along with available clinical data were included in this study. BRAF mutational status was determined by allele-specific real-time PCR between 2013 and 2020 at the Clinical Hospital Centre Rijeka. Of the 152 patients, 80 (52%) had BRAF-mutated melanoma, which showed a slight predilection for the trunk. Histologically, nodular melanoma was the most commonly associated subtype. No significant difference was observed in terms of disease progression and overall survival between BRAF-mutated and BRAF wild-type patients. However, in patients with BRAF-mutated melanomas, those who received BRAF inhibitors exhibited improved survival outcomes in advanced disease stages (p = 0.0025). Our study indicates that BRAF-mutated melanoma patients with distant metastases receiving BRAF inhibitors have significantly improved survival compared to those not receiving targeted therapy, supporting the clinical benefit of BRAF inhibitor use in appropriately selected patients.
Dear Editor,Basal cell carcinoma (BCC) is the most common malignancy worldwide. As a pragmatic approach, European Consensus classified BCC as easy totreat and difficult to treat. They defined difficulttotreat BCC as all locally advanced BCCs and also common BCCs with management problems due to technical difficulties or conditions related to the patient (1). Even surgery is the gold standard treatment for difficult to treat BCC; considering the treatment's potential risks and patients' preferences, alternative treatment modalities might be preferable. Immunocryosurgery, which is an innovative and minimally invasive combined therapeutic procedure, is one of these modalities with excellent efficacy even in challenging cases. Immunocryosurgery is based on the principle of activating the immune system against the tumor first, then triggering massive liberation of tumor antigens via destruction of tumor cells, and keeping the immune system activated against the tumor afterwards (2). The procedure's efficacy is 95 % after one cycle and 99 % overall (3); the five year tumorfree rate after one cycle is 91 % and 97 % overall (4) in BCCs smaller than 2 cm in diameter. In BCCs larger than 2 cm, the procedure's efficacy is approximately 75 % (2), and repetitive sessions may be required. These efficacy data are nearly comparable to standard surgical excision but with a significantly lower risk of complication (5). Here, a case with difficult to treat BCC treated with immunocryosurgery is presented. The 91 year old patient presented with a nonhealing wound on her nose. The lesion was painful and itchy. Her medical history included coronary heart disease, a history of myocardial infarction, coronary artery bypass grafting, and dementia. Dermatological examination revealed a 27 × 12 mm ulcer on her nasal tip with multiple actinic keratoses and severe solar damage (Figure 1). An incisional biopsy was performed with a preliminary diagnosis of basal cell carcinoma; histopathological examination confirmed the diagnosis with an ulceronodular subtype. The patient and her legal guardians were informed about treatment options. They denied classical surgical intervention because it would have required highrisk, extensive surgery. We decided to perform immunocryosurgery. She was given imiquimod 5 % cream daily for two weeks. At the end of the second week, open spray liquid nitrogen cryosurgery (two freeze-thaw cycles, 20 second freezing time each) was applied to the inflamed BCC and a 5 mm margin under local anesthesia. Imiquimod 5 % cream was continued for an additional three weeks; afterwards, a topical epithelising cream was applied until the healing process was completed. By the end of the eighth week, she had achieved a full clinical response (Figure 2), and her subjective symptoms had completely disappeared. During the 12 month follow-up, there was no recurrence. The key point of difficulttotreat BCC management is tailored treatment. All treatment modalities should be discussed with the patient, and decisions should be made together, considering not only tumor biology and risk factors but also the patient's preferences. Especially in patients of advanced age and with multiple comorbidities, it should be kept in mind that extensive surgeries may be complicated, increase morbidity, and reduce quality of life. Immunocryosurgery is an alternative and effective treatment that can save the day.
Dear Editor, Cutaneous metastases are a relatively rare skin condition, but when appear portrend unfavorable outcome of the disease. The most common skin metastases among women are those originating from breast carcinoma and melanoma. On the other side, melanoma, squamous cell carcinoma of the head and neck, lung, and colon carcinoma most commonly metastasize towards to the skin among men. The diagnosis of skin metastases often comes long after the primary cancer diagnosis (1,2). According to Globocan 2020 estimation, gastric carcinoma ranks as the fourth leading cause of cancer deaths for both genders combined (3). Cutaneous metastases of gastric carcinoma are rare, occurring in 0.2% - 2% of cases, predominantly in males (4). We present the case of a 63-year-old Caucasian woman who was referred to a dermatologist-oncologist due to the presence of multiple infiltrative, dark red plaques of varying sizes on her back in January of 2022 (Figure 1a). Dermatoscopic examination revealed orange-yellow patches, fine, short, and linear vessels, geometric, linear, and scattered perifollicular white scales, red dots, and spermatozoa-like structures (Figure 1b). Following a detailed review of her medical history, it was revealed that three years prior, she had undergone surgical treatment for gastric cancer with Krukenberg metastases. The surgery involved subtotal gastrectomy and hysterectomy with bilateral salpingo-oophorectomy. Post-operatively the patient received three cycles of cisplatin and 5-fluorouracil, followed by five cycles of capecitabine. The treatment resulted in successful locoregional control and reduced risk of relapse, until the apperance of skin lesions. These observations led the dermatologist-oncologist to suspect cutaneous metastases, prompting a biopsy of the skin plaques for pathohistological analysis, which subsequently confirmed metastatic deposits in the skin. The histopathological examination identified the cutaneous metastasis as originating from a poorly differentiated adenocarcinoma characterized by signet ring cells (Figures 2a and 2b). Considering the patient's history of gastric cancer surgery, a gastric origin for the metastasis was highly probable. However, due to an inconclusive immunohistochemical result, the possibility of breast tumor origin should be clinically ruled out. A mammography exam showed no signs of malignancy. MRI of the endocranium revealed leptomeningeal carcinomatosis, edema, and vein thromboses, as well as lesions in the cerebellum. Furthermore, metastatic deposits were observed in the scintigram of the right ribs (IV, V, IX) and the left ribs (VIII, IX), as well as Th9-Th1, L1-L5 vertebrae, and carpal bones. (Figure 2c) Cutaneous metastases of gastric carcinoma vary in presentation, commonly appearing as nodules, plaques or inflammatory telangiectatic lesions (5). Pathohistological examination depends on the malignancy's origin, typically showing intact epidermis, a free Grenz zone, and atypical cells in the dermis. If it is unable to confirm the primary tumor, immunohistochemical staining results of the skin are very valuable (6). In our case, immunohistochemical staining helped rule out underlying breast cancer. The pathogenesis of skin metastases is complex, often involving direct postsurgical implantation or hematogenous/lymphatic spread. Poorly differentiated adenocarcinomas, especially those with signet cells, have a higher incidence of delayed cutaneous metastases comparing to other gastric cancers. The concept of tumor dormancy could explain the belated appearance of cutaneous skin deposits, as it refers to the arrest of tumor growth or metastatic dissemination. In terms of cutaneous metastases, it means that isolated dormant micrometastases are clinically undetectable, causing neither symptoms nor any clinical signs for a long period (7-9). The pathway of awakening dormant cells leads to the relapse of the disease and the appearance of skin changes. The triggers for activation of dormant cells are not fully understood, but a handful number of reports suggest that the awakening of these cells is the final step of the metastatic outbreak (10). Our case confirms that manifestation of cutaneous metastases occurs at the terminal stage of the cancer disease, making it clear that timely therapy and vigilance for atypical skin changes are very important. This case underscores the need for a multidisciplinary approach to manage such manifestations.
Dear Editor, Melanoma is one of the most aggressive skin cancers, with rising global incidence (1). Prognosis is closely linked to the stage at diagnosis, with stage III, particularly cases involving lymph node metastases, carrying a high risk of relapse and mortality (2). Standard treatment includes wide local excision, sentinel lymph node biopsy, and systemic adjuvant therapy in metastatic cases (3). Despite these measures, five-year survival for stage IIIB melanoma remains significantly lower than for earlier stages (2). Herein, we report a rare case of stage IIIB melanoma with over ten years of relapse-free survival following surgical management alone, challenging typical prognostic expectations. A 70-year-old male was referred to our department in June 2011 after the excision of two melanomas: a superficial spreading melanoma (SSM) on the right forearm (Clark III, Breslow 1.1 mm) and a nodular melanoma on the upper back (Clark IV, Breslow 2.4 mm). On both locations wider surgical excision has subsequently been performed, according to contemporary guidelines for melanoma management, and sentinel lymph node biopsy in August 2011 revealed no metastases. The patient underwent routine surveillance with clinical exams, dermoscopy, and lymph node ultrasound. In October 2014, an enlarged left cervical lymph node was identified. Fine-needle aspiration was inconclusive, but surgical excision confirmed metastatic melanoma (Figure 1). A PET/CT scan in November 2014 revealed a hypermetabolic lymph node in region I of the left neck. A subsequent radical neck dissection in December 2014 removed eleven lymph nodes, none of which showed metastasis. The disease was classified as stage IIIB melanoma. The patient declined systemic therapy with vemurafenib. He later underwent surgical treatment for two new primary SSMs: one on the posterior neck in October 2016 (Clark II, Breslow 0.45 mm) and another on the left lumbar region in February 2019 (Clark II, Breslow 0.48 mm). Both were excised with clear margins and scar re-excisions. As of January 2025, the patient remains in remission with no signs of recurrence or metastasis, under continued follow-up with dermoscopy, lymph node ultrasound, and S100B monitoring, which is more than ten years after the diagnosis of metastatic melanoma. Stage IIIB melanoma is typically associated with a guarded prognosis, and systemic therapy is often recommended to mitigate the risk of relapse (2,3). The five-year melanoma-specific survival rate for this stage varies but is generally estimated at approximately 75% to 83% (2). Standard therapeutic protocols include BRAF inhibitors, MEK inhibitors, and immune checkpoint inhibitors, which have demonstrated significant efficacy in reducing recurrence and improving overall survival (3). However, not all patients are candidates for or opt to receive these treatments. The present case is exceptional due to the prolonged duration of relapse-free survival despite the absence of systemic therapy. The favorable outcome may be attributed to several factors, including early detection, complete surgical removal of all identified lesions, low tumor burden at the time of metastatic lymph node involvement, and the absence of ulceration or high mitotic activity. Furthermore, meticulous follow-up and adherence to surveillance protocols likely contributed to the timely identification and management of additional primary melanomas (4). Although adjuvant systemic therapy remains the recommended standard of care for stage IIIB melanoma, this exceptional case illustrates that, in rare circumstances, long-term remission may be achieved with surgery alone. Rather than challenging standard practice, this case highlights the need for research into prognostic and predictive biomarkers that could refine risk stratification within this heterogeneous disease stage.
Livedoid vasculopathy is a rare, chronic thrombo-occlusive disease characterized by recurrent livedoid skin changes, atrophic white plaques, and ulceration. It most commonly affects the dermal vessels of the distal lower extremities, ankles, and feet, bilaterally. While it is commonly associated with hypercoagulable states, systemic autoimmune diseases, and malignancies, we report a case of a previously healthy 31-year-old female with a history of moderate COVID-19 infection during pregnancy, two years before the onset of livedoid skin changes. The patient presented to a hematologist with a two-month history of erythematous to violaceous macules and patches on the dorsum of the feet, ankles, and lower extremities, along with mild ankle swelling. Multiple punch biopsies of the affected skin demonstrated thrombi, fibrinoid vascular changes, fibrosis, and hyalinization of the vessel walls - findings consistent with vasculopathy. Initial treatment included subcutaneous low-molecule weight heparin (dalteparin). This case highlights the importance of early recognition, the performance of a skin biopsy with subsequent histopathologic diagnosis, and appropriate management of this rare, but potentially debilitating condition.
Keloids are benign skin tumors resulting from deregulated wound healing processes, characterized by fibroblast hyperactivity, increased collagen deposition, and resistance to apoptosis. These lesions extend beyond the original wound borders and often cause significant physical and psychological burdens, including pain, pruritus, and reduced self-esteem. Despite advancements in medical science, keloid management remains a challenge due to the lack of standardized treatment protocols and the high recurrence rates associated with many therapeutic options. This review examines the efficacy and limitations of existing treatment modalities, including silicone gel sheets, antifibrotic agents, intralesional injections, cryotherapy, radiotherapy, laser therapies, surgical excision, and combination therapies. Emerging approaches, such as botulinum toxin, antihypertensives, platelet-rich plasma, and others, are also discussed. This article underscores the need for large-scale, high-quality studies focusing exclusively on keloids to refine treatment algorithms and advance therapeutic strategies.
Pemphigus, including its main subtypes of pemphigus vulgaris, pemphigus foliaceus and paraneoplastic autoimmune multiorgan syndrome (formally known as paraneoplastic pemphigus), is an autoimmune blistering disease which is characterized by acantholysis resulting from autoantibodies targeting epithelial cell surface antigens. Elderly patients with pemphigus face unique challenges pertaining to diagnostics and therapeutics. This review focuses on the special considerations which relate to the care of this patient group.
Accurate staging of high-risk melanoma patients is imperative to ensure effective and appropriate therapy but also to estimate the potential risk of recurrence. Despite numerous studies previously conducted, no consensus has been reached on the optimal posttreatment follow-up method for high-risk melanoma patients. There are no clear indications for PET/CT in follow-up or initial staging of clinically asymptomatic high-risk melanoma patients. The aim of our study was to determine the predictive value of preoperative PET/CT in staging of such patients and its implication on further therapeutic decisions. A retrospective cohort study of 85 patients with T3 and T4 melanoma without clinical signs of nodal involvement or distant metastases was conducted. Patients underwent PET/CT as a part of preoperative staging and results were compared with SLNB. In this study combined sensitivity and specificity of PET/CT for identifying regional and metastatic disease were 54% and 98%, respectively. The positive predictive value (PPV) of PET/CT was 95% while negative predictive value (NPV) was 71%. Preoperative PET/CT changed the treatment plan for 26 patients (31%) Our study showed that PET/CT certainly has a role in the preoperative staging of high-risk melanoma patients, but it also requires a mandatory sentinel lymph node biopsy afterwards.
Polypoid melanomas are unusual, as are amelanotic ones. Similarly, polypoid melanomas are not usually acral or amelanotic. They can be challenging to diagnose clinically, as they may resemble acral lentiginous nevus, polypoid Spitz nevus, eccrine poroma, schwannoma, pyogenic granuloma, verrucous carcinoma, fibrosarcoma, basal cell carcinoma, and pyoderma gangrenosum. We delineate a 64-year-old woman with an acral amelanotic polypoid melanoma on her sole. It was successfully removed surgically without limb amputation.
A 62-year-old caucasian male with an intellectual disability was referred due to two exophytic, pediculated, non-infiltrated perianal lesions of reddish-pink colour, surrounded by ten hyperpigmented brown macules in the gluteal area (figure 1). No relevant prior history was available. Histology showed marked acanthosis with surface erosion and exuberant neutrophil exocytosis; a dense plasmocytic inflammatory infiltrate was present (figure 2). Serological testing showed increased anti-treponemic IgG and IgM titers and RPR title of 1:128. Condylomata lata is a rare clinical manifestation of secondary syphilis consisting of pinkish or hypopigmented papules or plaques in the anogenital area. They are extremely infectious, and their recognition enables prompt diagnosis and effective therapy, with excellent prognosis.
Monkeypox is a viral zoonosis belonging to the genus Orthopoxvirus. Until now, cases of monkeypox were mostly isolated to endemic areas, however, many cases that do not even mention travel to the countries of Central and West Africa have appeared throughout Europe in the past year. The virus manifests itself as an outbreak of skin lesions followed by a general infectious syndrome. The frequent occurrence of skin lesions concentrated around the anogenital region was also seen in patients belonging to the MSM (Men Who Have Sex with Men) population, who admitted risky sexual relations. In this paper, we have presented a 28-year-old man who came to the University Clinical Center of Vojvodina with skin lesions in the genital area and was diagnosed with monkeypox infection by PCR multiplex from the lesions. The main goal of this case report is to determine the way the virus is transmitted and its clinical manifestations, to show diagnostic methods, as well as possible prevention measures and treatment options.
