A red nodule in the umbilicus of an older man.

Amelanotic melanomas (AM) are a difficult diagnostic challenge for clinicians. To consider the clinical presentation of AM, the histologic subtypes involved, the relationship with the diagnostic delay and the possible involvement in overall prognosis. Patients who were observed in our department to be affected by cutaneous melanomas were recorded. Sex, age, the clinical features, the site of presentation, the suspected diagnosis, the clinical course, the histological type, the Clark level and the Breslow thickness were recorded. AM were divided in three main clinical types: an erythematous macule or patch on sun-exposed skin, a dermal plaque or nodule without a particular epidermal change, an exophytic nodule. Only pure AM were considered. Histological subtypes considered were superficial spreading melanoma, nodular melanoma, and lentigo maligna melanoma. Diagnostic delay considered from when the patients first noticed the lesion on the site where the melanoma was diagnosed and when the physician or the patient first proposed the removal was recorded. The chi-squared test was used for statistical evaluation with P < 0.05 as level of significance. Thirty-six cases of AM out of a total of 500 melanomas (7.2%) were collected. The most frequent morphology of clinical presentation was the papulo-nodular form, followed by the plaque form. Mean Breslow thickness of AM was 1.72 mm compared to 0.61 mm of pigmented cases. Nodular histotype was highly represented in AM (30.5% of cases) with respect to pigmented nodular melanomas (2.9%). The diagnostic delay did not differ between amelanotic and pigmented melanomas, nor between nodular AM and nodular pigmented melanomas. The great prevalence of clinical and histological nodular cases, the higher mean Breslow thickness (considered as the most important factor of prognosis) of AM compared with a not significant greater diagnostic delay may point out that a good percentage of AM have an intrinsic faster speed of growth with a worse prognosis irrespectively of the diagnostic performance. The importance of educational campaign for patient and physicians is stressed.

JXG is a benign disorder of early childhood and primarily occurs in infants and children <2 years of age. It is characterized by solitary or multiple yellow-red nodules on the skin and, rarely, in other organs. The clinical diagnosis of solitary cutaneous JXG usually requires confirmation by biopsy. Referral to a dermatologist should be obtained to exclude other disorders if multiple lesions are present. Clinicians should rule out ocular lesions with referral to an ophthalmologist if the patient is <2 years of age and has multiple lesions of JXG. If ophthalmologic consultation reveals no ocular lesions, screening every 6 months for the first 2 years of life is advised.

Spitz tumors are known to harbor fusions in tyrosine receptor kinases (TRKs). These include ROS1, NTRK1, ALK, and RET.1-5 We are beginning to parse out the molecular findings and associated morphologic features on hematoxylin and eosin (H&E) slides of Spitz and Spitzoid lesions.1 The lineage of some of these can be determined using fusion-related morphologic clues, in conjunction with molecular confirmation. Here we present a case of a healthy 22-year-old male with a family history of melanoma. He presented to the clinic with a 3 mm red papule on his right posterior helix, present for several months before bleeding (Figure 1). The clinical differential diagnosis favored a cherry angioma or pyogenic granuloma versus less likely a basal cell carcinoma or amelanotic melanoma. A shave biopsy demonstrated a dermal melanocytic population of relatively small nests of melanocytes, some spindled, with occasional rosette-like structures (Figure 2). Several mitotic figures were identified in the superficial and deep dermis with an absence of maturation. Immunohistochemistry showed MART-1, PRAME, and pan-TRK positivity. p16 was lost. FISH analysis demonstrated loss of PTEN and an NTRK1 fusion, supporting a diagnosis of an NTRK1 Spitz melanoma with a Breslow depth of at least 2.1 mm. The patient was referred to ENT surgery and given no clinical evidence of metastatic disease; no imaging was performed prior to wide local excision and sentinel node biopsy. At 1 year following the initial diagnosis, the patient underwent PET/CT scan that showed no melanoma recurrence or spread. The patient is currently undergoing regular skin exams. This case highlights a challenging clinical presentation of an amelanotic Spitz melanoma, clinically favored to be a benign angioma or pyogenic granuloma. Of interest, it was molecularly characterized to harbor an NTRK1 fusion and had the associated histological morphology on H&E. NTRK1 fusion Spitz lesions are often flat-based, exophytic lesions under microscopy and have a distinct morphology of a flat base, filigree-like rete ridges, smaller nests, more spindled cells, rosette-like structures, and nevocytoid cytology.2, 4, 5 Under high power imaging, filigree-like rete ridges which are elongated, thin, and branching are another distinctive feature of NTRK1 fusion Spitz lesions.4 These lesions are the most likely of the Spitz neoplasm fusions to have Kamino bodies. Alternatively, BRAF fusions tend to have more epitheloid cells with high-grade nuclear pleomorphism and a sheet-like, rather than an organized nested, growth pattern.5 ALK fusions tend to be clinically larger in diameter and histologically, they are wedge-shaped with plexiform architecture and large nests of spindled cells.2, 4, 5 ROS1 fusions show melanocytes in confluent whorling nests with prominent transepidermal elimination of melanocytic nests and mucinous changes.5 In summary, this challenging clinical case of an amelanotic Spitz melanoma highlights the utility of identifying histologic fusion clues and obtaining the proper molecular testing for Spitz or Spitzoid melanomas.

Background. Nonpigmented skin neoplasms are a significant problem in the practice of dermatovenereologists and cosmetologists, as they can resemble inflammatory dermatoses, mimic benign skin tumors, reducing oncological alertness of both doctors and patients. Amelanotic (nonpigmented) melanoma is an extremely aggressive nonepethelial malignant tumor that develops from melanocytes but has no pigment. Skin melanoma morbidity has increased in the last 10 years by a factor of 1.5 and amounted to 70.4 cases per 100 thous. population as of 2021. Melanoma occupies the first place in terms of mortality among all skin tumors. Objective. To describe the most common nonpigmented skin neoplasms, focusing on their clinical and dermatoscopic diagnosis. Material and methods. A non-systematic review of domestic and foreign sources on the studied topic, which was performed using a continuous sampling in PubMed, RSCI and eLibrary databases using the following keywords: amelanotic melanoma, basal-cell carcinoma, seborrheic keratosis, angiokeratoma, pyogenic granuloma, dermatoscopy as well as their combinations. The information presented in original studies and reviews of literature, as well as the results of own research, namely a total of 30 sources were analyzed. The search depth was 18 years, years of search: 2004—2022. Results. The most common nonpigmented skin tumors were described: basal-cell carcinoma, amelanotic melanoma, seborrheic keratosis, vascular tumors. Approaches to their clinical and dermatoscopic diagnosis were presented. Relatively little studied amelanotic skin melanoma is particularly dangerous. The analysis of clinical and dermatoscopic features of amelanotic melanoma was performed based on own clinical observations and literature data. Conclusion. Removal of nonpigmented skin neoplasms with their subsequent histological examination should be the gold standard of diagnosis, which allows to exclude amelanotic melanoma.

Nonmelanoma Skin Cancer

The correct assessment of a solitary red nodule in clinical practice is of crucial importance, amelanotic melanoma being the most important differential diagnosis. Dermoscopy is nowadays a pivotal tool in the management of skin tumors, however it has some limitations in the evaluation of nonpigmented lesions, in which the diagnosis is merely based on the evaluation of the vascular pattern. Recently, reflectance confocal microscopy has been introduced as a new, noninvasive technique for the diagnosis of skin lesions. Confocal microscopy provides skin imaging in vivo at cellular level resolution, close to conventional histology. We present a series of clinical scenarios of red nodules, including melanoma metastasis, pyogenic granuloma, eccrine poroma, Spitz nevus and dermatofibroma. Reflectance confocal microscopy examination added important information to the clinical diagnosis and subsequent management in all cases except for dermatofibroma. We discuss the advantages and limitations of this technique in this particular field of application.

Significant unexplained and unintentional weight loss was found in 45 elderly patients who were identified by computer search of the diagnostic files of seven family practice centers. We performed a case series chart review study which revealed that 24% of the 45 cases had no definitive etiology for the weight loss after two years of extensive clinical investigation. Depression was found to be the most common diagnosis made (18%) followed by cancer (16%). Only four patients died during the study period and all had cancer. The most prevalent diagnosis in this group of ambulatory elderly patients did not prove to be cancer, as often though, but rather "unexplained weight loss." CT scans were not found to be helpful as screening tests in the evaluation of weight loss. Using the data from this study, the diagnostic evaluations of elderly patients with unexplained weight loss may be more efficiently directed.

Intrapulmonary Bronchogenic Cysts: Computed Tomography, Clinical and Histopathologic Correlations

Background: Vesiculobullous disorders (VBDs) are extant with diverse clinical manifestations. Vesicles and bullae are fluid-filled cavities present within or beneath the epidermis. They are autoimmune blistering disorders in which autoantibodies are directed against target antigens present in the epidermis and dermo-epidermal junction. Objective: Evaluation of the various clinicodemographic profile of patients with a pattern of distribution (subtypes) of VBDs of the skin and assess the association between clinical aspects and histological changes in vesiculobullous lesions of the skin. Materials and Methods: The study material constituted 93 cases of VBDs out of 936 skin biopsies reported over two and a half years (January 2016 to June 2018) from the tertiary care center. A detailed history of the patients was taken, and a complete physical and dermatological examination with findings including clinical diagnosis was recorded. Histopathological examination (incisional/excisional/punch biopsy) was done in each case. The clinico-demographic evaluation was done and the results were correlated with histopathological findings. Results: Vesiculobullous lesions constituted 10.06% of all skin biopsies. The majority of cases were of pemphigus vulgaris (PV) 30 (32.25%) followed by 16 (17.2%) of bullous pemphigoid. In 83 cases (89.24%) histopathology findings were consistent with clinical diagnosis. Out of 34 cases that were diagnosed clinically as PV, the histopathological study proved 30 cases (88.23%) as PV. Conclusion: Vesiculobullous lesions of the skin are a heterogeneous group of disorders. It is essential to differentiate each pattern of subtype based on clinical examination and histopathological findings. Histopathological diagnosis with clinical correlation plays a major role in arriving at the diagnosis.

Macroscopic discrimination between amelanotic malignant melanoma (aMM) and the so-called granuloma pyogenicum (GP) is often uncertain since reliable criteria for a clear differentiation of either growth are lacking. In a search of such criteria we analysed the data of 57 consecutive in-patients with cutaneous aMM and of 83 with GP presenting at our Department during the years 1970-1988. The following items were compared with each other: duration from growth onset to definite diagnosis, site of growth, age and sex of the patients. Significant differences (p less than 0.01) between either growth were found for all items evaluated. Our results substantiate the hitherto gained impression of a remarkably shorter median history of GP as compared to aMM (5 vs. 26 weeks). Furthermore, aMM prevailed in elder (age greater than 50 years) particularly female (70%) patients, whereas GP developed about equally in both sexes and at all ages. Site distribution was also found to differ for either growth (GP predominantly in the head and neck region, rarely on lower limbs; aMM in all areas, rarely on the trunk). These data yield additional measures for clinical distinction between aMM and GP.

A young adult presented with a four-month long history of hemoptysis. A computed tomography (CT) scan showed a mid-trachea lesion (Figure 1). A flexible bronchoscopy was performed and revealed a cherry-like polyp (Figure 2(a)) and biopsy resulted in brisk bleeding. The polyp was coagulated at the base with a Nd-YAG (neodymium doped-yttrium aluminium garnet) laser followed by forceps resection via the rigid bronchoscope (Video). Histology of the 8 mm by 10 mm lesion was classic of a lobular capillary hemangioma (LCH) (Figure 3). The patient had been asymptomatic since and bronchoscopy performed two years later showed no tumor recurrence (Figure 2(b)). Figure 1 Computed tomography showed a homogeneously contrast enhanced polyp (white arrow) on the left lateral wall of the mid-trachea. Figure 2 (a) Distinct cherry-like polyp consistent with hemangioma arising from the left lateral wall of the mid-trachea depicted on bronchoscopy. (b) Bronchoscopy performed two years later revealed a small scar induration with normal mucosa (arrow) overlaying ... Figure 3 A nodular lesion with squamous metaplasia (marked downwards thick arrow) of the surface epithelium, underlying fibrinous exudates (marked ∗), and a florid proliferation of small capillaries (marked →) surrounded by fibrous stroma on 10x ... Lobular capillary hemangioma (LCH) is typically found on cutaneous and oronasal mucosa. Tracheobronchial LCH is a rarity [1]. Hemoptysis often occurs for a short duration ranging from weeks to months with the exception of one reported case of massive hemoptysis which required arterial embolization. The airway lesion is usually small (<10 mm), sessile, or polypoid with a distinctive glinting vascular (cherry) appearance that bleeds easily. Pathogenesis of this benign tumor is unclear and has been correlated to infections, trauma, and hormonal shifts [1]. The latter can be supported by the case of a rapidly growing trachea LCH (40 mm by 20 mm) found in a pregnant lady who presented with critical airway obstruction [2]. The characteristic findings of a homogeneously contrast enhanced lesion seen on CT scan and an airway lesion (as described above) observed during bronchoscopy should lead to a cautious biopsy to clinch the diagnosis. Bronchoscopic ablative intervention often results in a cure although past reports had a follow-up of one year or less. Ablative modalities included endoscopic resection with Nd-YAG laser, argon plasma coagulation, electrocautery, cryotherapy, and forceps. In one reported case of tumor recurrence, brachytherapy was applied.

Pyogenic granuloma (PG) is a benign vascular neoformation, presenting as a painful red nodule on the skin, mucosa or nail apparatus. It is usually related to local complications such as bleedings and superinfections. The etiology of PG remains still unclear, and several triggers can lead to its formation. In case of multiple lesions, systemic conditions and drugs remain the main causes. Antineoplastic treatments, retinoids, antiretrovirals, hormones and anticonvulsants are frequently implicated in PG formation. In literature, PG has been rarely described in the course of biological treatment due to rheumatological disease. The present case report describes the development of polydactolous PGs in a 21-year-old woman with juvenile systemic lupus erythematosus (jSLE) during treatment with belimumab, a monoclonal antibody directed against BlyS. The clinical presentation, in particular the timing and the multiplicity of the lesions, and the improvement after belimumab discontinuation allowed us to consider PG as drug-induced. This case highlights the importance of considering PG as a potential complication of rheumatologic treatments.

GP130-STAT3 Regulates Epithelial Cell Migration and Is Required for Repair of the Bronchiolar Epithelium

To evaluate the diagnostic patterns and factors that may influence delays in the diagnosis of pemphigus vulgaris (PV) with oral involvement. In this prospective cohort study, 36 newly diagnosed PV patients with oral involvement were clinically examined and interviewed about the natural history of the oral lesions, number of medical consultations (Med consultation), medical treatment history, and diagnostic delay time (DD time). Thirty (83%) PV patients presented initially with oral mucosal involvement (OMI) and 6 (17%) presented initially with skin involvement (SI). The mean DD time was 6.19±3.82months, and the mean number of Med consultation was 5.8 (n=36). The means of all the parameters were significantly higher for the OMI patients than for the SI patients (P<.05). All of the patients with OMI had been misdiagnosed. The DD time was significantly longer in patients who presented initially with desquamative gingivitis (8.25±3.81) than patients who presented with ulcers and erosions (4.78±1.11) (P<.05). There was a statistically significant positive correlation between DD time and Med consultation (r=0.91). Even with the high frequency of oral involvement and easy access to the oral cavity, diagnostic delays are still common for patients with oral PV. This underlines the need for education to improve healthcare providers' awareness and knowledge of the clinical oral presentation of PV.

Amelanotic melanoma (AMM) presenting as pyogenic granuloma and occurring in the vicinity of acquired melanocytic nevi is rare. Herein, we report such a manifestation in a 68-year-old male who presented with the painful red nodule and multiple pigmented patches involving the left great toe. Histopathological examination of skin biopsy taken from the nodule with an immunohistochemical study using HMB45 and S-100 confirmed the diagnosis of AMM. Biopsy from the pigmented patch near the nodule showed features of melanocytic nevus. Investigative work up revealed metastatic deposits in the left inguinal lymph node with no evidence of systemic involvement, placing him in malignant melanoma Stage IIIC of American Joint Committee on Cancer (AJCC) tumor node metastasis system. The development of AMM in the vicinity of acquired melanocytic nevi and manifesting as granuloma pyogenicum is unique in this case.