Evaluation of the prognostic significance of clinical features of tumoral lesions in an extensive series of mycosis fungoides.

BACKGROUND: Tumors indicating the advanced stage of mycosis fungoides (MF) have a rich clinical spectrum. Although it is known that the prognosis of MF generally worsens following the development of tumors, some cases may have a relatively indolent course, and the role of clinical characteristics regarding prognosis has still not been well understood. METHODS: MF patients were retrospectively evaluated regarding the development of tumors. Besides demographic characteristics, data of the subtype and stage of the disease were recorded. The clinical features of tumors, including number (<5, 5-10, 11-20, or >20), location, dimension (diameter of ≥5 cm), presence of ulceration, and surrounding inflammation, were noted. Univariate and multivariate analyses evaluated the relationship between overall survival (OS) with demographic and clinical features. RESULTS: Among 730 consecutive MF patients, tumors developed in 8.2% (n = 60), of whom 46.7% were diagnosed with advanced-stage MF from the beginning. The most common subtype was folliculotropic MF (53.3%). Most patients (55%) had multiple tumors, and the most frequent localization was the trunk (71.7%). Most tumors presented as smooth-surfaced, indurated papules and/or nodules (70%), while others were reddish-purple, occasionally accompanied by ulceration (50%), perilesional inflammation (23.3%), and attaining large dimensions (25%). Mortality was recorded in 51.7% of patients, and the 5-year OS rate from the diagnosis of tumors was 49%. Independent poor prognostic factors for OS in multivariate analysis included older age at the time of diagnosis, presence of tumors at the initial MF diagnosis, presence of over 20 tumors, and the existence of large tumors. CONCLUSIONS: Tumoral MF seen in older patients, the first diagnosis of MF in this stage, presenting with generalized and large tumors, seems to be a predictive factor for OS.

Gorlin Syndrome: A Comprehensive Evaluation of Skin Findings.

OBJECTIVE: Although Gorlin syndrome has rich skin findings, there is limited information about their subtypes, features specific to this genodermatosis, and relationships with each other. MATERIALS AND METHODS: The demographic characteristics as well as cutaneous and extracutaneous findings of consecutive Gorlin syndrome patients diagnosed during 23 years were evaluated retrospectively. The relationship between palmoplantar pitting and basal cell carcinoma (BCC) in this localization and the relationship between odontogenic keratocysts (OKCs) and epidermoid cysts were investigated. RESULTS: A total of 30 patients were diagnosed with Gorlin syndrome of whom 36.7% were children. BCC was the most common finding (90%) followed by OKCs (83.3%), skeletal system anomalies (76.7%), and palmoplantar pitting (76.7%). While classical BCC (63.3%) lesions were the predominant clinical subtype among all patients, acrochordon-like or small-sized papular BCCs were seen in 45.4% of pediatric patients. Three patients, 2 of whom were children, had BCC lesions in the palmoplantar region in association with palmoplantar pitting. Epidermoid cysts presenting clinically as solitary (n = 12) or a few nodules (n = 4) without punctum, located more commonly in acral areas (n = 10) were seen in 16 (53.3%) patients of whom 7 were children. Epidermoid cysts were seen in 60% of patients with OKCs, and the relationship between epidermoid cysts and OKCs was not statistically significant (P = .15). Extracutaneous tumors such as medulloblastoma (n = 3), cardiac fibroma (n = 1), and ameloblastoma (n = 1) were also recorded. CONCLUSION: The awareness of papular or acrochordon-like BCCs, palmoplantar BCCs, and acral epidermoid cysts without punctum may facilitate early diagnosis of Gorlin syndrome in children.

Evaluation of secondary malignancies in a large series of mycosis fungoides.

BACKGROUND: An increased risk of Secondary Malignancies (SMs) in Mycosis Fungoides (MF) has been suggested previously. However, the relationship between this risk and the features of MF is not well-known. OBJECTIVE: To investigate the rate and types of SMs in a large cohort of MF patients focusing on the associated features of these patients. METHODS: The demographic features, subtype, and stage of MF, as well as the temporal relationship between the diagnosis of MF and the development of SMs were determined. Major clinical features of MF in this group were compared with MF patients without association of SMs. RESULTS: Among 730 MF patients with a mean follow-up period of 67.9 ± 52.4 months, 56 SMs were identified in a total of 52 (7.1%) patients. While 28.8% of patients were previously diagnosed with other malignancies, then subsequently had a diagnosis of MF, it was vice versa in 53.8% of patients. Most of the SM-associated MF patients had early-stage (80.7%) and classical type of MF (86.5%) without a significant difference from MF patients without association of SMs; 85.5% and 72.5%, respectively. The most commonly identified SMs were hematologic malignancies (64.3%) including lymphomatoid papulosis (n = 22), Hodgkin's lymphoma (n = 4), non-Hodgkin's lymphoma (n = 5), polycythemia vera (n = 2). Other most commonly associated malignancies were breast cancer (n = 4), prostate cancer (n = 3), renal cell carcinoma (n = 2), melanoma (n = 2), and Kaposi's sarcoma (n = 2). STUDY LIMITATIONS: A single tertiary dermatology center study with a retrospective design. CONCLUSION: Apart from the well-known lymphomatoid papulosis association, systemic hematological malignancies were also quite common in the large cohort of MF patients.

Oral mucosa involvement in pediatric patients with xeroderma pigmentosum: a comprehensive review.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV-induced DNA damage. This can lead to the development of neoplasms affecting multiple organ systems, with onset often in childhood. Unfortunately, no cure currently exists for XP, and management strategies focus on sun protection and early intervention for malignancies. Although most skin problems in XP patients are UV induced, various oral lesions are also described. However, the literature has not extensively characterized the oral manifestations and their prognostic significance. METHODS: We conducted a comprehensive review to evaluate the prevalence and nature of oral mucosal lesions in pediatric XP patients. RESULTS: Our literature search yielded 130 pediatric XP patients with oral involvement and 210 associated tumoral or non-tumoral lesions. Squamous cell carcinoma was the most common type of oral mucosal tumor reported, with other malignancies including basal cell carcinoma, melanoma, angiosarcoma, fibrosarcoma, and trichilemmal carcinoma. CONCLUSION: Given the potential morbidity and mortality associated with oral mucosal tumors in XP patients, our study aims to raise awareness of these manifestations. Early diagnosis and treatment are crucial for managing these lesions effectively, and routine oral exams should be considered a critical component of dermatological evaluations for XP patients, especially in the pediatric age group.

Evaluation of secondary malignancies in a large series of mycosis fungoides

Abstract Background An increased risk of Secondary Malignancies (SMs) in Mycosis Fungoides (MF) has been suggested previously. However, the relationship between this risk and the features of MF is not well-known. Objective To investigate the rate and types of SMs in a large cohort of MF patients focusing on the associated features of these patients. Methods The demographic features, subtype, and stage of MF, as well as the temporal relationship between the diagnosis of MF and the development of SMs were determined. Major clinical features of MF in this group were compared with MF patients without association of SMs. Results Among 730 MF patients with a mean follow-up period of 67.9 ± 52.4 months, 56 SMs were identified in a total of 52 (7.1%) patients. While 28.8% of patients were previously diagnosed with other malignancies, then subsequently had a diagnosis of MF, it was vice versa in 53.8% of patients. Most of the SM-associated MF patients had early-stage (80.7%) and classical type of MF (86.5%) without a significant difference from MF patients without association of SMs; 85.5% and 72.5%, respectively. The most commonly identified SMs were hematologic malignancies (64.3%) including lymphomatoid papulosis (n = 22), Hodgkin's lymphoma (n = 4), non-Hodgkin's lymphoma (n = 5), polycythemia vera (n = 2). Other most commonly associated malignancies were breast cancer (n = 4), prostate cancer (n = 3), renal cell carcinoma (n = 2), melanoma (n = 2), and Kaposi's sarcoma (n = 2). Study limitations A single tertiary dermatology center study with a retrospective design. Conclusion Apart from the well-known lymphomatoid papulosis association, systemic hematological malignancies were also quite common in the large cohort of MF patients.

Annular skin tumors and lymphoproliferative diseases.

Determining the shape of a skin lesion may provide a diagnostic clue in dermatology practice, more commonly for inflammatory diseases but also for skin tumors. The annular formation may develop by diverse mechanisms in skin tumors. Annular lesions may occur from the onset of the tumor as sparing the central area or depression and/or ulceration in the center of the tumor or outward expansion of the primary lesion. Clustering of multiple papulonodular lesions sparing the central area or relatively independent processes acting on the central and peripheral components of the tumor may also result in an annular appearance. We have explored a wide variety of benign and malignant skin tumors and lymphoproliferative diseases forming an annular shape.

Eyelid involvement of primary cutaneous lymphomas: A clinical perspective.

Eyelids may be affected in systemic, ocular adnexal and primary cutaneous lymphomas (PCLs). The frequency of eyelid involvement in PCLs is still not well known and it is not a predilection site for any type. While primary cutaneous T-cell lymphomas (CTCLs) are more commonly seen than primary cutaneous B-cell lymphomas (CBCLs), especially mycosis fungoides (MF) as by far the most frequent type, B cell lymphomas are reported to be the commonest type in eyelid localization on the contrary. PCLs may be located on the eyelids, as the sole manifestation or in association with the involvement of other parts of the eye and elsewhere of the body. MF may present with a rich spectrum of clinical features on the eyelids mostly seen in folliculotropic subtype and advanced-stage disease. Erythematous scaly patches or plaques representing the most commonly encountered eyelid MF lesions may mimic many other dermatological conditions. Diffuse thickening, oedema, poikilodermic changes, atrophy and wrinkling are other suggestive findings of eyelid MF. Milia-like papules, madarosis and ectropion are also seen in the folliculotropic variant of MF, as ectropion is more typical for Sezary syndrome. Eyelids are also a typical location for tumoural MF which has been suggested as a poor prognostic indicator in MF. Papulonodular lesions, large tumours, ulceration, diffuse infiltration, oedema and subcutaneous atrophy on the eyelids may also be seen in other types of PCLs. Keep in mind, the rich clinical spectrum of PCLs on the eyelids may be crucial in early diagnosis in this special localization.

Annular skin tumors and lymphoproliferative diseases.

Determining the shape of the skin lesion may provide a diagnostic clue in dermatology practice, more commonly for inflammatory diseases but also for skin tumors. The annular formation may develop by diverse mechanisms in skin tumors. Annular lesions may occur from the onset of the tumor as sparing the central area or depression and/or ulceration in the center of the tumor or outward expansion of the primary lesion. Clustering of multiple papulonodular lesions sparing the central area or relatively independent processes acting on the central and peripheral components of the tumor may also result in an annular appearance. We have explored a wide variety of benign and malignant skin tumors and lymphoproliferative diseases forming an annular shape.

Comprehensive mastocytosis data analysis from a single center.

Mastocytosis is a very rare disorder and is divided into three prognostically distinct variants by World Health Organization: Cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma or localized mast cell (MC) tumors. The wide range of complaints may cause patients to consult various clinics, with resulting mis- or underdiagnosis. Therefore, cooperation between different subspecialties is of paramount importance. In this article, we have compiled 104 adult mastocytosis cases diagnosed and followed in our Hematology and other clinics. 86 (82.7%) of 104 patients had systemic mastocytosis. Osteoporosis, disease-related complications, and secondary malignancies are important topics in this group. We know that indolent form has great survival. But smoldering or aggressive mastocytosis has a poor prognosis. CM and indolent SM have a significantly better prognosis compared to aggressive SM (p < 0.001). We found that the presence of more than 25% of mast cells in the bone marrow, the presence of concomitant marrow dysplasia, and the presence of disease-related complications affect survival (p < 0.001). In addition to the WHO classification, the IPSM scoring system is indicative of the prognosis in this rare disease.

Secondary Localized Cutaneous Amyloidosis is not Rare in Bowen's Disease and Bowenoid Papulosis.

Secondary localized cutaneous amyloidosis is a histopathological finding seen in the dermis, in various benign, premalignant, and malignant skin conditions, without clinical significance. The real incidence is not known. We aimed to investigate the phenomenon of secondary localized cutaneous amyloidosis in Bowen's disease and Bowenoid papulosis. We retrospectively evaluated the data of all cases with histopathological confirmation of Bowen's disease and Bowenoid papulosis between 2006 and 2017 in our Dermatovenereology and/or Pathology departments. Secondary localized cutaneous amyloidosis was observed in three patients with Bowen's disease (3/52; 5.8%) and in three patients with Bowenoid papulosis (3/18; 16.7%). Herein, we present the demographic, clinical and histopathological features of these six cases of secondary localized cutaneous amyloidosis in detail. Although the occurrence of secondary localized cutaneous amyloidosis in epithelial tumors is a well-known phenomenon, its incidence has not been previously reported in Bowen's disease and Bowenoid papulosis. Therefore, our results indicating a high incidence may be particularly important for Bowenoid papulosis, as its association with secondary localized cutaneous amyloidosis has only been shown in one case before. Moreover, in three of six cases, we histologically observed areas of regression with a marked prominence of amyloid deposition. Remarkably, two of these patients had a history of topical application of destructive agents which reveals a possible etiologic relationship between secondary localized cutaneous amyloidosis and cellular apoptosis/necrosis induced by these external agents.

Skin tumors in xeroderma pigmentosum: Evaluation of a large series and a literature review.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare genodermatosis with a lifelong propensity to develop malignant skin tumors. METHODS: In this retrospective study, 24 XP patients were evaluated with regard to frequency and clinicopathological features of benign and malignant skin tumors. RESULTS: Seventeen patients had at least one malignant skin tumor diagnosed: basal cell carcinoma (BCC) in 13 patients (n = 72), basosquamous carcinoma in three patients (n = 4), squamous cell carcinoma in six patients (n = 13), keratoacanthoma in three patients (n = 15), and melanoma in six patients (n = 18). Most melanomas (n = 15) were in situ lesions. Several benign skin tumors were noted such as tricholemmoma (n = 1), trichoepithelioma (n = 1), trichoblastoma (n = 1), follicular infundibulum tumor (n = 1), keratoacanthoma-like follicular lesion (n = 1), adnexal tumors with folliculosebaceous (n = 1) and tricholemmal differentiation (n = 1), and neurofibroma (n = 1). Benign vascular proliferations including pyogenic granulomas (n = 8), widespread telangiectasias, and senile angioma-like lesions were also observed in 3, 5, and 5 patients, respectively. CONCLUSIONS: Similar to many reports, BCC was found to be the most common malignant skin tumor. The high prevalence of benign adnexal tumors of follicular differentiation, some of them showing mixed histopathological features and various vascular proliferations in our series raises the question of whether they indicate a formerly undescribed association with XP.

Evaluation of Associated Lymphomas and Their Risk Factors in Patients with Lymphomatoid Papulosis: A Retrospective Single-Center Study from Turkey

Objective: Lymphomatoid papulosis (LyP) is an indolent skin disease with variable clinical features classified among the primary cutaneous CD30+ T-cell lymphoproliferative disorders. It may show association with cutaneous and systemic lymphomas. We aimed to identify the frequency and characteristics of associated lymphomas among Turkish patients with LyP and to determine the risk factors for secondary lymphomas. Materials and Methods: The files of patients diagnosed with LyP between 1998 and 2018 in a tertiary dermatology clinic were retrospectively analyzed. Univariate and multivariate models were used to assess the possible risk factors for secondary lymphomas, such as demographic and clinical characteristics of the patients. Results: Among 61 patients (47 adults, 14 children) with LyP, a total of 22 secondary lymphomas were observed in 20 patients. Nineteen of them were adults. Mycosis fungoides (MF) was the major associated lymphoma (n=19) followed by systemic anaplastic large cell lymphoma (ALCL) (n=2) and primary cutaneous ALCL (n=1). The most common stage in patients with accompanying MF was stage IB (n=11). While 18 patients showed the classical type of MF, one patient had folliculotropic MF. When the risk factors for association between LyP and other lymphomas were evaluated, only older age was found to be a significant risk factor and existence of ulcerated lesions was found to be a negative indicator. Conclusion: LyP is not rare in the pediatric population. MF is the most common associated lymphoma in patients with LyP. Adult LyP patients are more commonly associated with secondary lymphomas than pediatric patients. Older age at the time of diagnosis of LyP is a significant risk factor for associated lymphomas.

Efficacy of narrow-band ultraviolet-B therapy in patch-stage mycosis fungoides: A clinical study and review of the literature.

BACKGROUND/PURPOSE: We investigated the efficacy of narrow-band UVB in patch-stage MF and reviewed the literature to re-evaluate the role of this phototherapy method in early MF. METHODS: Early-stage MF patients treated with narrow-band UVB were included. Number of narrow-band UVB treatment sessions, treatment duration, cumulative UV dose, clinical response results, side effects, duration of the remission period and relapse rate were evaluated. RESULTS: Complete response rate was 86.7% in sixty patients with MF. Mean number of treatment sessions was 62.9 ± 15.1, treatment duration was 32.1 ± 10.7 weeks, and mean cumulative UV dose was 62.1 ± 41.9 J/cm2 in patients with complete response. Mean duration of remission was 10.3 ± 11.0 months, and relapse rate was 70% in a mean follow-up of 21.9 ± 16.4 months. Mild regional erythema (6.7%) and pruritus (8.3%) were main side effects. There were no significant differences between stage IA and stage IB patients in terms of treatment parameters and duration of remission period. CONCLUSIONS: Our study confirms that narrow-band UVB is effective for the management of the patch-stage MF without serious side effects. Extent of the skin lesions did not affect the efficacy of phototherapy. However, due to the short duration of remission, a further option such as an optimal maintenance therapy protocol should be considered.

The Spectrum of Underlying Causes of Iatrogenic Kaposi's Sarcoma in a Large Series: A Retrospective Study.

BACKGROUND: The frequency of clinicoepidemiological variants of Kaposi's sarcoma (KS) differs markedly throughout the world. The iatrogenic variant is mainly associated with the use of immunosuppressive therapy. AIMS: We aimed to investigate the distribution of KS variants in our practice and elucidate the underlying causes of iatrogenic KS. METHODS: Consecutive KS patients seen in a single tertiary center were grouped according to the tumor variants and iatrogenic KS patients were evaluated about associated conditions. RESULTS: Among 137 patients, classic variant was the most frequent presentation (n = 88), followed by iatrogenic (n = 37) variant. Among the iatrogenic group, ten were transplant recipients. In 16 iatrogenic KS patients, systemic corticosteroid was used, in four for myasthenia gravis (MG) and in three for rheumatoid arthritis. In three patients, KS developed under topical corticosteroid (TC) treatment. Among iatrogenic KS patients, ten of them had a second primary neoplasm and one had congenital immunodeficiency syndrome. CONCLUSIONS: Our study revealed one of the highest rates for iatrogenic KS (27%) reported in the literature. Besides well-known causes, relatively frequent association with MG was remarkable. Usage of different forms of TCs was the cause of KS in a few cases.

Lichen Sclerosus on the Sites of Striae Distensae and a Surgical Scar in a Patient with Coexistent Morphea.

Lichen sclerosus (LS), also known as lichen sclerosus et atrophicus, is a chronic inflammatory mucocutaneous disease affecting the genital and/or extragenital areas. Although LS usually occurs alone, its coexistence in morphea patients has been reported in 5.7% and 38.0% (genital LS) of cases, in two series (1). A 74-year-old woman presented with a 6-month history of multiple asymptomatic, shiny , indurated, brownish large flat plaques located on the abdomen (Figure 1, a-b) and back, intermingled with slightly atrophic, white-colored, guttate, and patchy areas (Figure 1, d-e). Both punch biopsies of the sclerotic plaques on the back and abdomen showed findings consistent with morphea (Figure 1, c, f). Furthermore, the punch biopsy of a well-demarcated white plaque on the back revealed findings compatible with LS (Figure 1, f). Remarkably, there were also multiple white-colored lesions on the sites of pregnancy-induced striae distensae (SD) (Figure 2, a-b) on the lower abdomen and an old appendectomy scar (Figure 2, c). There was no anogenital involvement. A diagnosis of morphea-LS overlap was established and white lesions located on the surgical scar and SD were clinically evaluated as LS. Methotrexate (15 mg/week) achieved a partial regression of morphea plaques in three months. However, white LS lesions remained unchanged. Our patient presented with coexistence of LS and morphea on different sites of the trunk and on the same lesion. Additionally, one of the isolated LS lesions was located on a surgical scar. Occurrence of LS on skin grafts, irradiated areas, injection sites, or burn/surgical scars has been attributed to the Koebner phenomenon, also called isomorphic response, defined as "the formation of the skin lesions in the same morphology of the existing disease on the areas of various cutaneous injuries" (2). LS is classified under the Koebner category-III (occasional lesions) (2). However, in a case of morphea with features of LS that developed in 1 month following a herpes zoster infection has been suggested to represent "Wolf's isotopic response" (3), which was originally defined as "the occurrence of a new skin disease at the site of another, unrelated and already healed skin disorder" with a time interval between the first and second diseases ranging from months to several years (4). Remarkably, typical morphea plaques in our patient did not involve the surgical scar, in contrast to a cohort in which 16% of 329 patients developed initial morphea lesions at sites of prior (surgery) or ongoing/repetitive (chronic friction) skin trauma (5). SD appear on skin as atrophic linear bands mostly due to rapid weight changes, pregnancy, Cushing syndrome, or prolonged use of corticosteroids (6). The mechanism underlying the occurrence of several diseases on striae is still elusive. Blunt trauma occurring during the development of striae has been suggested to cause the Koebner phenomenon in patients with vitiligo, psoriasis, and lichen planus (7), but it has been suggested that the occurrence of leukemia cutis on SD in a patient reflects Wolf's isotopic response (8). Although chronic graft-versus-host disease, urticarial vasculitis, keloid, lupus erythematosus, diffuse normolipemic plane xanthoma, and drug-induced cutaneous eruptions have been reported to occur on striae (6,9), such an association with LS as in our patient has not been previously documented in the literature. Concomitant occurrence of LS patches on different previous lesions such as a surgical scar and SD in our patient raises the possibility of a common underlying mechanism. As mentioned above, the terms "Koebner phenomenon" or "Wolf's isotopic response" have been used to designate the development of some diseases in injured areas. However, Happle and Kluger (10) claimed in a recent statement that "there is no clear-cut criterion to distinguish isotopic response from Koebner phenomenon and all reactions of this kind represent examples of Koebner phenomenon", which seems to be the best way to describe the site-specific occurrence of LS lesions in our patient.