Cutaneous rhabdomyosarcoma with FUS::TFCP2 fusion: A case report emphasizing early detection.

Rhabdomyosarcoma with TFCP2 rearrangement is a recently identified malignant neoplasm characterized by immunohistochemical evidence of rhabdomyoblastic differentiation, keratin expression, upregulation of ALK, and an aggressive clinical course. This neoplasm has a tendency to affect craniofacial bones, with only a few reported cases of extra-osseous tumors. Here, we present a case of cutaneous rhabdomyosarcoma with FUS::TFCP2 fusion in a 35-year-old female. Notably, the tumor exhibited a pathologic spectrum, initially resembling sclerosing dermatitis at presentation but progressing into a high-grade malignant tumor within 8 months. The distinctive immunoprofile of this neoplasm highlights the importance of early molecular studies for diagnosis, even in the presence of low-grade cytomorphology. Early detection may offer an opportunity for timely resection before the tumor becomes unresectable.

Melanocytic tumors with spitzoid morphology: correlation of clinicopathologic features and FISH analysis.

BACKGROUND: A subset of melanocytic tumors with spitzoid morphology may lead to potential inaccurate diagnosis and lack of assessment of malignancy potential. In this study, we aimed to evaluate melanocytic tumors with spitzoid morphology using conventional melanoma FISH (RREB-1, CCND1, MYB and CEP6) and 9p21 FISH (CDKN2A) probes and compare the probe results with clinical and histopathological features. METHODS: This study is a multicentric retrospective study including three centers, Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Pathology, Acibadem University, School of Medicine, Department of Pathology and ETA Pathology Laboratory. The pathology reports in archives of these three centers between 2015 and 2017 have been reviewed for cases diagnosed as atypical Spitz tumor or melanoma with Spitzoid features. These cases were selected for the study. We analyzed 39 cases of atypical Spitz tumor (AST), 10 cases of melanomas with spitzoid features for clinicopathological data and chromosomal alterations, targeting RREB-1 (6p25), CCND1 (11q13), MYB (6q23), together with 9p21 (CDKN2A), using FISH methodology. RESULTS: Thirty out of total 49 cases showed chromosomal alterations by 4-probe melanoma FISH assay, 22 (56.4%) cases were ASTs, and 8 (80%) cases were melanomas. Eighteen out of 49 cases showed homozygote deletion by 9p21 FISH assay, 12 (30.8%) cases were ASTs, and 6 (60%) cases were melanomas. When histopathological data were compared with FISH results, a statistically significant correlation was found between 9p21 FISH positivity (homozygous deletion) and presence of deep mitosis (p < 0.05). In addition, epidermal consumption (p = 0.07) and increased mitotic activity (p = 0.05) were more frequent in cases with homozygous 9p21 deletion, but these differences did not reach statistical significance. When the clinical features were considered, there was a statistically significant correlation between 9p21 FISH positivity and the diameter (p < 0.05). There was no statistically significant correlation between melanoma FISH assay and any of the histopathological or clinical data. DISCUSSION: These data suggest that 9p21 FISH positivity correlated with more worrisome histopathologic and clinical features, such as deep mitosis, increased mitotic activity, epidermal consumption, and larger lesion size, so these features are precious, pointing out spitzoid lesions with higher risk. However, there is a need for further studies using FISH or similar techniques in order to provide more accurate prognostic information in lesions Blank morphology.

Analysis of interobserver reproducibility in grading dysplastic nevi: Results of the application of the 2018 World Health Organization grading criteria.

BACKGROUND: We aimed to determine whether the histopathological grading of dysplastic nevi is an objective endeavor, considering interobserver variability, according to 2018 World Health Organization (WHO) criteria. METHODS: In total, 179 cases of dysplastic nevi, with high and moderate degree of atypia, diagnosed and graded according to the previous criteria were reviewed by three pathologists. Then, the observers graded the dysplastic nevi as low or high according to 2018 WHO criteria. RESULTS: Grading of dysplastic nevi was in complete agreement in 99 out of 179 cases across three observers with a fair level of overall interobserver agreement (multirater κfree : 0.40). The observers showed moderate to good agreement for most of the architectural features, except for criteria regarding focal continuous basal proliferation of melanocytes, density of non-nested junctional melanocytes, and presence of dyscohesive nests of intraepidermal melanocytes, whereas fair agreement was achieved for the cytological criteria. CONCLUSIONS: The 2018 WHO criteria for dysplastic nevus will ensure a common approach to the diagnosis and grading of dysplastic nevi. However, histopathological criteria, such as cytological features and focal continuous basal proliferation of melanocytes, should be improved so as to ensure a more accurate surgical approach and risk assessment.

Livedoid cutaneous metastasis of signet-ring cell gastric carcinoma.

Cutaneous metastasis of gastric cancer is extremely rare. Nodular forms are more common and inflammatory forms are exceptionally encountered. Herein, we report a case of inflammatory cutaneous metastasis of signet-ring cell gastric cancer (poorly cohesive gastric carcinoma with signet-ring cell component) masquerading as livedo reticularis. To our knowledge, such a clinical presentation of cutaneous metastasis has not been reported for gastric cancer. It is imperative to preserve a high index of clinical suspicion for diagnosing cutaneous metastases. Our case highlights the importance of obtaining a skin biopsy in patients with a known history of internal malignancy. Bizarre, newly erupting, evolving, persistent, or treatment-refractory dermatologic lesions (such as nodules, ulcers, erythematous, reticular, or livedoid patches) might be clues for an underlying internal malignancy and require prompt histopathological sampling. Personal medical history, histopathological examination, and immunohistochemical profiling are equally important in distinguishing primary cutaneous carcinomas from secondary metastatic deposits. Early recognition of a cutaneous metastasis might enable appropriate staging and timely intervention, thereby prolonging survival.

Proliferating Pilar Tumors: Can Immunohistochemistry Differentiate Benign and Malignant Forms?

BACKGROUND: Proliferating pilar tumor (PPT) is an adnexal tumor of purported differentiation toward the follicular outer root sheath. Immunohistochemistry has been suggested to differentiate between benign and malignant forms. METHODS: Eleven benign (PPT) and 9 malignant PPT lesions were reviewed; Ki67, p27, and p53 were applied. The staining intensity (strong, moderate, weak, and negative), positive cell numbers, and marker indexes (%) were scored using image-analysis software (ViraSoft). RESULTS: Overall, there was no significant correlation between Ki67 and p53 and histopathological features. However, malignant PPTs had significantly lower numbers of p27-positive cells (P = 0.030). CONCLUSIONS: Our study includes the largest group of patients in whom image analysis of p53, Ki67, and p27 has been used to try to separate benign from malignant lesions. Although there were no significant differences regarding Ki67 and p53, malignant lesions have a statistically lower expression of p27. Further studies may be needed to determine the clinical usefulness of image analysis in this differential diagnosis.

Terminal osseous dysplasia with pigmentary defects (TODPD) in a Turkish girl with new skin findings.

Terminal osseous dysplasia with pigmentary defects (TODPD; MIM #300244) is an extremely rare, X-linked dominant, in utero male-lethal disease, characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibromatosis of childhood. Delayed/abnormal ossification of bones of the hands and feet, joint contractures, and dysmorphic facial features may accompany. A single recurrent mutation (c.5217 G>A) of the FLNA gene which causes cryptic splicing was identified as the cause of the disease. We here present the first TODPD case from Turkey with full-blown phenotype who exhibit unique additional findings, hypopigmented patch on the lower extremity following Blaschko's lines and smooth muscle hamartoma of the scalp in review of all the previously reported TODPD cases.

Margin-Controlled, Staged Surgical Excision in the Treatment of High-Risk Basal Cell Carcinomas of the Head and Neck Region.

BACKGROUND: The most common skin cancer is basal cell carcinoma (BCC), and the gold-standard treatment for high-risk tumours is Mohs surgery. However, alternative methods are needed for high-risk tumours in countries where the performance rate of Mohs surgery is low. OBJECTIVES: The objective of this article is to investigate the feasibility, efficacy, and safety of margin-controlled, staged surgical excision (MCSSE) in high-risk tumours as a possible treatment alternative. METHODS: A retrospective cohort study, including patients diagnosed with high-risk BCC in the head and neck region and treated with MCSSE between 2003 and 2010, was conducted. RESULTS: During the study period 50 tumours in 47 patients were treated, with low adverse event rates and high patient satisfaction rates. Of the 50 tumours, 1 recurred at the 12-month follow-up. CONCLUSIONS: Despite the small sample size and relatively short follow-up period, the present study shows that MCSSE might be a feasible alternative for the treatment of high-risk BCCs in institutions where Mohs surgery is not performed. Future studies on long-term recurrence rates are needed.

Circle hair: report of two cases and brief review of the literature.

Circle hair (CH) is an interesting subtype of ingrown hair, characterized by the growing of hair shaft in a spiral or circular morphology underneath a translucent layer of stratum corneum, parallel to skin surface. In contrast to rolled hair (RH), neither perifollicular inflammation nor abnormal follicular keratinization are known to accompany CH. The reason why the hair shaft grows circumferentially and transversely under the skin instead of emerging through an apparently open hair follicle ostium and growing vertically remains to be determined. Although CH is a frequent benign incidental finding in normal skin examination, reports on this disorder are scarce. Herein we report two cases of CH and briefly review the existing literature. We believe that CH develops because of trauma in patients having a genetic susceptibility for this disorder and that CH is more common than the relevant medical literature suggests.

Poxvirus-Induced Vascular Angiogenesis Mimicking Pyogenic Granuloma.

The orf virus, a member of poxvirus family, is a zoonotic parapoxvirus endemic in many countries, mostly seen among sheep, goats, oxen, and may be transmitted to humans. Orf virus infections may induce ulceration, papulonodular, pustular, or ecthyma lesions in the skin. Rarely, orf virus provokes extensive vasculoendothelial proliferation by encoding an apparent homolog of the mammalian vascular endothelial growth factor family of molecules. The vascular endothelial growth factor-like viral gene product is expressed early during infection and could be responsible for the induction of endothelial proliferation. Here, a 6-year-old male patient with poxvirus-induced widespread vascular angiogenesis is presented, which developed ten days after a thermal burn.

Evaluation of high-risk features of primary enucleation of patients with retinoblastoma in a tertiary center of a developing country in the era of intra-arterial chemotherapy.

PURPOSE: To evaluate the frequency of high-risk histopathologic factors in Turkish children enucleated for retinoblastoma and to analyze the association between growth pattern, rosetta formation, tumor thickness, presence of necrosis, calcification, neovascularization, rate of mitosis, and high-risk histopathologic factors. METHODS: Pathology reports of 59 eyes who had received enucleation for retinoblastoma were reviewed retrospectively. The histopathologic data included presence of choroidal invasion, optic nerve invasion, scleral extension, tumor thickness, presence of necrosis, calcification, neovascularization, rosetta formation and lymphocyte infiltration, rate of mitosis, and growth pattern. RESULTS: This study included 59 eyes from 30 (50.8%) male and 29 (49.2%) female patients. The mean age was 22.87 ± 18.99 months. There were 30 (50.8%) eyes with choroidal invasion, 30 (50.8%) eyes with optic nerve invasion, and 5 (8.5%) eyes with scleral invasion. Endophytic growth pattern was seen in 27 (45.8%) eyes, exophytic growth pattern was seen in 2 (3.4%) eyes, and combined growth pattern was seen in 30 (50.8%) eyes. Exophytic growth pattern was found statistically related to choroidal invasion (p = 0.00). Although tumor with greater thickness tended to have more choroidal invasion (p = 0.02), there was no relation between tumor thickness and optic nerve invasion (p = 0.09). CONCLUSIONS: Incidences of choroidal and optic nerve invasion showed similarity with other developing countries. Because of higher incidence of high-risk factors, intra-arterial chemotherapy with its targeted effect should be preferred carefully.

Approach to cutaneous vasculitides with special emphasis on small vessel vasculitis: histopathology and direct immunofluorescence.

PURPOSE OF REVIEW: The present review will focus on recent publications in cutaneous vasculitides. RECENT FINDINGS: Some histopathological and clinical features, such as papillary dermal edema, perivascular C3 deposition, clinically evident edema, and lesions above the waist, may point out renal or gastrointestinal involvement in Henoch-Schönlein purpura (HSP). HSP associated with familial Mediterranean fever differs from typical isolated HSP by showing no deposits of IgA, much younger age, and location of the lesions on the face or the trunk. Single-organ cutaneous small vessel vasculitis is a more restricted entity than hypersensitivity vasculitis and HSP. Because cutaneous polyarteritis nodosa and macular lymphocytic arteritis share some clinicopathologic features, the question is raised whether they are not two different entities. Several histopathological features defining IgG4-related disease are found in granuloma faciale and erythema elevatum diutinum, two localized chronic cutaneous vasculitis; however, in a recent series no diagnostic criteria for IgG4-related disease was detected in them. SUMMARY: When a patient presents with skin lesions, in which necrotizing or leukocytoclastic vascuitis is confirmed histologically, irrespective of the size of the affected vessel, the possibility of systemic vasculitis, an infection, medication, or a systemic disease such as systemic lupus erythematosus must be searched before reaching definitive diagnosis.

Pyoderma Vegetans Misdiagnosed as Verrucous Carcinoma.

Pyoderma vegetans, a rare disorder of the skin, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis. It is clinically characterized by large verrucous plaques with elevated borders and multiple pustules. Here, the authors report the case of a 33-year-old man who was misdiagnosed as having verrucous carcinoma for 4 years.

Interstitial Mycosis Fungoides With Lichen Sclerosus-Like Clinical and Histopathological Features.

Mycosis fungoides (MF) simulates a variety of dermatologic disorders histopathologically and clinically, well deserving the designation of a great mimicker. Interstitial MF is a rare, but well-recognized histopathological variant resembling the interstitial form of granuloma annulare or the inflammatory phase of morphea. From a clinical standpoint, MF can have a wide array of manifestations, including an anecdotal presentation with lesions clinically suggestive of lichen sclerosus (LS). We herein report a 25-year-old man with a history of patch-stage MF who later developed widespread LS-like lesions histopathologically consistent with interstitial MF. In some biopsies, additional features resembling LS were discerned. We think that our case might represent a unique variant of interstitial MF presenting with LS-like lesions. The diagnostic challenge arising from this uncommon presentation is discussed together with review of the literature.

Successful treatment of pityriasis lichenoides chronica with narrow-band ultraviolet B therapy in a patient with Keratitis-Ichthyosis-Deafness syndrome: a case report.

Keratitis-ichthyosis-deafness (KID) syndrome is a rare genodermatosis causing ichthyosis-like skin lesions, keratitis, and deafness. Herein, we report a patient with this rare syndrome in association with pityriasis lichenoides chronica, which was succesfully treated with narrow-band ultraviolet B phototherapy despite our concerns regarding the increased risk of squamous cell carcinoma, hyperpyrexia, and keratitis.

Histopathological and clinical evaluation of papulopustular lesions in Behçet's disease.

OBJECTIVES: Behçet's disease (BD) is a chronic inflammatory disorder characterised by aphthous stomatitis, genital ulcerations, erythema nodosum-like manifestations and papulopustular lesions. While a neutrophilic vasculitis accompanies most skin lesions it is usually regarded that the papulopustular lesions in BD are similar to acne vulgaris (AV). The aim of our current study was to further assess the clinical and histopathological features of papulopustular lesions in BD and how these features compared to those of AV. METHODS: To analyse the histopathological features of BD and AV, 89 punch biopsies were taken from 58 BD (52 male, 6 female) and 31 AV patients (26 male, 5 female). Sections were evaluated in a blind manner by two different pathologists. A dermatologist who was blind to the patients' diagnosis counted the number of papules, pustules, comedones, folliculitis, cysts and nodules on the face, chest, back, upper and lower extremities. RESULTS: The number of papules, pustules and comedones was higher on the face in the AV group, whereas in the BD group, both number of papules and folliculitis on the back and that of folliculitis were higher on the lower extremities in the AV group. With the exception of comedone formation, which was more frequent among the AV patients [20/31 (64.5%) vs. 23/58 (39.6%), p=0.025] the presence of suppurative folliculitis/perifolliculitis, intrafollicular abscess formation, leukocytoclastic vasculitis or microorganisms were not useful in differentiating BD from AV. However, the interobserver agreement for histologic assessment was low. Kappa was 0.17 for suppurative foliculitis/perifol¬liculitis; 0.39 for intrafollicular abscess formation; 0.51 for leukocytoclastic vasculitis. CONCLUSIONS: In the BD group, although the inflammatory lesions located on the face were less than those in the AV group inflammatory lesions such as folliculitis on the legs were only seen, again in the BD group. The papulopustular lesions of BD could not be distinguished from AV by histology. Some of this might be due to high interobsever variation in interpretation. Acne is an inherent manifestation of BD.

The clinical features and histopathologic patterns of folliculotropic mycosis fungoides in a series of 38 cases.

BACKGROUND: The recognition of folliculotropic mycosis fungoides (FMF) may pose diagnostic challenges, owing to the variety of histopathological findings. OBJECTIVE: In this study, our aim is to describe the broad spectrum of the histopathological patterns in a total of 86 biopsies from 38 patients with FMF, together with the clinical features. RESULTS: The most frequent histopathologic pattern was the folliculocentric/folliculotropic pattern, with or without follicular mucinosis. Keratin-filled cysts and comedones were the second most common pattern in the biopsies. Other less common findings included widening of the hair follicle orifis with keratotic plugging, reminiscent of keratosis pilaris, granuloma formation, eosinophilic or suppurative folliculitis and basaloid folliculolymphoid hyperplasia. Coexisting syringotropism was present in some biopsies. The CD4 : CD8 ratio was at least 4 : 1 or more in most biopsies. Grouped follicular papules and patch/plaque lesions with follicular prominence were the most frequent clinical findings. Folliculocentric lesions such as milia, cysts and acneiform lesions, alopecia, loss of hair or eyebrows were also seen. In 6 out of 38 (15.8%) patients, transformation to large-cell lymphoma was observed during the follow-up. CONCLUSION: The awareness and the identification of the various histopathological presentations of FMF by pathologists, as well as by clinicians, are imperative to prevent diagnostic errors.