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Dear Editor, The Leser-Trélat sign is a rare paraneoplastic cutaneous marker of internal malignancy characterized by sudden eruption of multiple seborrheic keratoses (SK). It is mostly associated with gastrointestinal adenocarcinomas (gastric, colon, rectal), and less frequently with breast cancer and lymphoproliferative disorders/lymphoma (1). It can be also associated with lung, kidney, liver, and pancreas malignancy (1). Pruritus occurs in half of the patients. Lesions rarely require any treatment, as they mostly tend to resolve once management of the underlying malignancy has started (2). A 32-year-old female patient with family history of colorectal cancer presented with an acute eruption of SK. She reported that the first symptoms were the loss of appetite and intense pruritus. The brown papules appeared over a period of 2-3 months, first on her back, then on the abdomen, thorax, neck, and lasty on the extremities (Figures 1a and b.). Physical examination showed numerous brown hyperkeratotic papules and plaques on the trunk, neck, and extremities. The patient complained of night sweating, epigastric pain, and heartburn. Over the last three months, she had lost over 15 kg. The patient had experienced an episode of acute gastritis 10 years ago and had been treated for Helicobacter pylori infection 4 years ago. Laboratory results showed elevated sedimentation rate and decreased levels of hemoglobin, erythrocytes, and hematocrit. CA-19-9 and CEA levels were elevated. Gastroscopy with multiple biopsies confirmed gastric adenocarcinoma. An abdominal CT scan revealed enlarged retroperitoneal lymph nodes. SK withdrew after total gastrectomy and commencement of chemotherapy. The Leser-Thrélat sign was named after two surgeons, Edmund Leser and Ulysse Trélat, who described the eruption of cutaneous lesions in patients with cancer (3). However, the correlation between multiple SK and internal malignancy was described by Hollander in 1900 (4). Acute eruption of SK has also been reported in some other cases, such as benign tumors, pregnancy, human immunodeficiency virus infections, use of adalimumab, and others, which indicates that the Leser-Trélat sign is not highly specific (5). It is also somewhat controversial whether a sudden appearance of SK can be considered a marker for internal malignancy, since both SK and malignancies occur more frequently in the elderly population, thus allowing for a higher likelihood of coincidence (6). However, the patient in this case was young and therefore less likely to suddenly develop such a large number of SK, which are more commonly seen after the age of 50 (7). Although the pathogenesis of Leser-Thrélat sign is not fully understood, there are data suggesting an association with tumor-secreting growth factors including epidermal growth factor and transforming growth factor-alpha, both of which can stimulate the epidermal growth factor receptor (8). Sudden appearance of eruptive SK is uncommon in young patients. This specific sign highlights the importance of considering internal malignancy in the differential diagnosis of patients presenting with eruptive SK.

Objective: to report a possibly novel complication of laser hair removal., Case Report: a white-skinned 18-year-old patient discovered an umbilical, brown, and raised lesion while shaving before his second diode laser hair removal session. He sought consultation before his fourth laser session since the lesion further thickened and darkened. Dermoscopy showed no pigmented network, but a few comedo-like openings within an erythematous-light brown scaly and fissured papule, "moth-eaten" borders, and a central crust due to manipulation, suggesting the diagnosis of seborrheic keratosis. We noted that the laser fluence was increased on the umbilical region where hair seemed resistant to treatment. The patient denied a recent history of local sun tanning, sunburns, inflammation, drainage, or manipulation. The lesion cleared, with no short-term relapse, after one session of cryotherapy., Conclusion: the development of a seborrheic keratosis-like lesion on a densely haired non-sun-exposed umbilicus of a young patient, following pre-laser shaving and high-fluence hair removal diode laser sessions, could have implicated triggering irritation and/or keratinocyte stimulation by red light-engendered reactive oxygen species (ROS) in the skin with silent epidermal mosaicism.

Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase ( GDA ) has been identified to cause UV-induced keratinocyte senescence in seborrheic keratosis. Seborrheic keratosis is also frequently pigmented. Growing evidences indicate that hyperuricemia is a risk factor of acanthosis nigricans, an acquired skin hyperpigmentation. The objective of this study was to investigate role of GDA and its metabolic end product, uric acid, in hyperpigmentation of patients with seborrheic keratosis using their lesional and non-lesional skin specimen sets and cultured primary human epidermal keratinocytes with or without GDA overexpression or uric acid treatment. GDA -overexpressing keratinocytes or their conditioned media containing uric acid increased expression levels of MITF and tyrosinase in melanocytes. Uric acid released from keratinocytes was facilitated by ABCG2 transporter with the help of PDZK1 interaction. Released uric acid was taken by URAT1 transporter in melanocytes, stimulating melanogenesis through p38 MAPK activation. Overall, GDA upregulation in seborrheic keratosis plays a role in melanogenesis via its metabolic end product uric acid, suggesting that seborrheic keratosis as an example of hyperpigmentation associated with photoaging.

Background: Basaloid tumors arising from seborrheic keratosis (SK) that resembled basal cell carcinoma (BCC) were infrequently observed in our patients. They also exhibited morphologic features similar to those of trichoblastoma or basaloid follicular hamartoma., Methods: We retrospectively collected cases of SK with basaloid tumors from 2001 to 2017. Ten cases of BCC, five of nevus sebaceus with trichoblastoma, five of trichoblastoma, and five of trichoepithelioma were included as controls. Tumor-associated antigens Bcl-2, CD10, PHLDA1, and CK20 were tested. Antigenic markers CD34 and CD10 were used to analyze peritumoral stroma features and Ki-67 and pHH3 to measure the mitotic activity., Results: Ten cases of SK with basaloid tumors were found and all located in non-sun-exposed areas, including five men and five women, with a mean age of 61 years. A distinct PHLDA1 staining was not observed. The staining patterns of basaloid tumor lobules associated with SK were similar to the benign control group. Bcl-2 staining in the tumor lobules was mostly negative. Peritumoral CD10 stain and CK20-positive Merkel cells in the lobules were observed and the mitotic counts were low., Conclusion: Basaloid tumors arising from SK are not always BCC. They were all benign follicular hamartomatous proliferation in this case series., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Seborrheic keratosis (SK), whose appearance is generally a small roundish reddish to brownish scaling lesion ranging in size from a few mm to many mm, may have a single presentation or be one of many such lesions. Because it is a commonly encountered lesion on the face, trunk, or extemities and is readily recognized clinically, it is infrequently biopsied. When the lesion has an unusual pattern or has become irritated, it may rarely mimic a malignancy,Most patients ignore such common age spots; however, others may have concern about their appearence, in which case the SKs have been surgicaly excised. In recent retrospective studies and case reports, SKs have rarely been found to have malignant characteristics. Although these studies are inconclusive, lesions that are inflamed, bleeding, ulcerated, or sufficiently irritated may require being biopsied to rule out melanoma or other malignancies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Seborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described., Objective: To describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions., Methods: There were 162 cases of SCC-SK in a span of a decade (2003-2014). All of the histopathologic specimens and medical records were reviewed. Data from these patients were compared to a control group with seborrheic keratosis who were matched by age, sex, and location of lesion from the same time period (n = 162)., Results: SCC-SK has the classic histopathologic features of SK, such as hyperkeratosis, parakeratosis, papillomatosis, and pseudohorn cysts. The areas of squamous cell carcinoma were characterized by areas of squamous dysplasia (100%), hypogranulosis (79.6%), squamous eddies (79.6%), solar elastosis (80.9%), and brown pigmentation (59.9%). Patients with a history of immunosuppression had an increased risk for developing SCC-SK (19% vs 3%; P < .01), particularly when inhibition was transplant-associated (10% vs 0%; P < .01)., Limitations: This was a single center, retrospective study., Conclusion: SCC-SK occurs more often in elderly men with a history of immunosuppression associated with organ transplants., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Positron emission tomography (PET) is an examination based upon the uptake of a radioactive tracer by hypermetabolic cells. It is primarily used in tandem with tomodensitometry (PET-TDM) for cancer staging because of its high sensitivity and specificity for the detection of metastases. However, unusually high uptake may occur with benign tumours, including skin tumours. Herein, we report an extremely rare case of pathological uptake levels resulting from seborrhoeic keratosis., Patients and Methods: A 55-year-old male patient with oesophageal squamous-cell carcinoma was referred to us following the discovery of an area of high marker uptake following PET-TDM and corresponding to a pigmented skin lesion. No other areas of suspect high uptake were seen. The lesion was surgically excised and histological examination indicated seborrhoeic keratosis. The histological appearance was that of standard seborrhoeic keratosis without any notable mitotic activity., Discussion: PET-TDM is an examination that enables diagnosis of malignancy. However, rare cases have been described of increased marker uptake by benign cutaneous tumours such as histiocytofibroma, pilomatricoma and condyloma. To date, there have only been only very few cases of increased uptake due to seborrhoeic keratosis., Conclusion: This extremely unusual case of increased glucose uptake in PET-TDM due to seborrhoeic keratosis confirms that the hypermetabolic activity detected by this examination is not necessarily synonymous with malignancy and that confirmation by clinical and histological findings is essential. The reasons for increased metabolic activity within such benign tumours are not known., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Hereditary hemochromatosis is an autosomal recessive disorder that disturbs iron metabolism and results in iron deposition throughout the body. Iron accumulation in various organs may cause a wide range of systemic symptoms and cutaneous manifestations of the disease are particularly striking. Classically, hereditary hemochromatosis has been termed "bronze diabetes." Although diffuse hyperpigmentation is a well-described feature of this disease, other cutaneous symptoms may also occur, and a variety of anomalies may be observed. We present a case of long-standing hereditary hemochromatosis associated with hypopigmented plaques, which were found to be seborrheic keratoses on histologic examination. The cutaneous findings in hereditary hemochromatosis are summarized and an unusual case of seborrheic keratosis manifesting as hypopigmented plaques in a man with hereditary hemochromatosis is described. PubMed was used to search the following terms: hemochromatosis, hereditary, hyperpigmentation, hypopigmentation, keratosis, melanin, seborrheic, siderosis. Despite the generalized hyperpigmentation that is usually observed in hereditary hemochromatosis, seborrheic keratosis may present rarely as hypopigmented lesions in individuals affected by this disease. Therefore, seborrheic keratoses should be considered in the differential diagnosis in hemochromatosis patients who present with uncharacteristic pigmentation.

Paraneoplastic itch occurs as the result of a systemic reaction to an underlying malignancy. Paraneoplastic itch is most commonly associated with lymphoproliferative malignancies and solid tumors that result in cholestasis. Paraneoplastic itch may occur in the absence of a primary rash or in association with dermatologic conditions such as erythroderma, acanthosis nigricans, dermatomyositis, Grover's disease, and eruptive seborrheic keratosis. Treatment of paraneoplastic itch is centered on targeting the underlying malignancy responsible for the systemic reaction. In cases of malignancy that are refractive to treatment, other therapies have been found to be effective for paraneoplastic itch, including selective serotonin reuptake inhibitors, mirtazapine, gabapentin, thalidomide, opioids, aprepitant, and histone deacetylase inhibitors., (© 2016 S. Karger AG, Basel.)

Background: Seborrheic keratoses (SK) are the most common cutaneous neoplasm in humans. Given their numbers, a squamous cell carcinoma in situ (SCCIS) arising from an SK would not be unexpected, although this occurrence has not been widely reported., Objective: This study compares the immune status of patients with a SCCIS arising contiguously from SK (SK/SCCIS) and the number of daily medications taken by these patients. The biopsy tissue was evaluated for the presence of human papillomavirus DNA., Methods: Over a 5-year period at our institution, 13 cases of SK/SCCIS were diagnosed. For each case, age- and sex-matched control patients with a histologically diagnosed unremarkable SK were randomly selected. The number of patients taking immunosuppressing medications was determined from each group and compared statistically. In addition, polymerase chain reaction analysis of the 13 SK/SCCIS biopsies was performed., Results: Five of the 13 study patients took immunosuppressive medications compared to none of the 39 control patients (P = 0.0005). None of the biopsies demonstrated the presence of human papillomavirus DNA by polymerase chain reaction., Conclusions: Immunocompromised patients with SKs appear to carry a greater risk of these otherwise innocuous lesions developing an SCCIS, although given the small number of patients evaluated, further research into this possible association is warranted., (© 2014 The International Society of Dermatology.)

Introduction: Gluten enteropathy (celiac disease) is a chronic disease and presents as diarrhea, weight loss and anemia., Case Presentation: A 35-year-old Caucasian man with gluten enteropathy, familial multiple lipomas and seborrheic keratosis was seen in our clinic. After confirmation of the diagnosis, he was advised to follow a gluten-free diet. His clinical improvement was evaluated and confirmed with biopsy., Conclusion: Celiac disease is known to be associated with many systemic diseases and skin lesions but its association with familial multiple lipomas has not yet been reported.

Reports of seborrheic keratosis (SK) with concurrent malignant tumors are rare, but previous and recent reports - especially the co-manifestation of basal cell carcinomas (BCC) have added to the ongoing debate of the possibility of the development of BCC from SK. We report a rare case of SK with underlying BCC with scarcely accounted histopathological characteristics - reticulated type and nodular type, respectively - that showed no direct histological link between the two entities. We also carefully suggest that differences in histopathology (whether the two lesions are connected or not) may account for the possibility of incidental co-habitation., (© 2013 Japanese Dermatological Association.)

We report a 66-year-old male presenting with malaise, heartburn and pruritic seborrheic keratoses in both feet of sudden onset, suggesting a Leser-Trélat sign. An upper gastrointestinal endoscopy disclosed a gastric cancer. The patient was subjected to a total gastrectomy and during follow up, the skin lesions had disappeared.

Leser-Trélat sign is a controversial paraneoplastic phenomenon characterized by an eruption of seborrheic keratoses (SKs). We report a rare case of eruptive inflammatory SKs in a man undergoing induction chemotherapy for acute myeloid leukemia (AML). We also review the literature on Leser-Trélat sign.

Segmental neurofibromatosis (SNF) is a rare variant of neurofibromatosis (NF) type 1 characterized by a restricted distribution of cafe-au-lait macules, and/or neurofibromas, and rarely freckling to a single dermatomal segment. Patients with NF type 1 have an associated increased risk for benign or malignant tumours. The prevalence of typical NF type 1 complications including malignancies in SNF is much lower than the generalized form. Seborrheic keratosis is one of the more common benign epidermal tumour which can be a paraneoplastic syndrome when it arises with an eruptive appearance. To our knowledge in the literature no case of SNF associated with eruptive seborrheic keratoses has been defined. We report the case of a man, aged 51, who had SNF and abruptly developed eruptive seborrheic keratoses.

Mark, 54 years of age, has a nontender lump on his praecordium that has been present 'for a long time'. He vaguely recalls a smaller lump at the same site years ago, which he squeezed, with subsequent resolution. Mark denies any bleeding, however, he has noticed occasional yellowish-brown stains on his shirt.

A 76-year-old man consulted to our hospital complaining of a black tumor of the temporal head. The tumor was nodular mass measuring 1 × 1 × 0.6 cm and black. A clinical diagnosis of basal cell carcinoma was made, and an excision with wide margins was performed. Histologically, the tumor was symmetrical, with horny keratinization in the center. An aggregate of atypical cells regarded as malignant cells was present in the center. No invasion was recognized. The cells were heavily pigmented. Mitotic figures, individual keratinization, and clumping cells were also recognized. Numerous dendritic melanocytes were recognized in the malignant lesion. Immunohistochemically, strong p53 expression was present in all malignant cells, and the malignant cells showed a high Ki-67 labeling of 60%. They were negative for melanosome and S100 protein and positive for cytokeratins. The periphery of the tumor showed typical features of pigmented reticulated seborrheic keratosis. There were gradual merges between the two lesions. This case suggests that pigmented Bowen disease can arise in pigmented reticulated seborrheic keratosis.

Background: Trichoblastomas (TBs) are benign follicular tumors that can present either as solitary nodule or as multiple facial papules. Only one case of sporadic TB in a composite tumor has been reported, arising in an apocrine poroma. We report the association of TB and benign epidermal/follicular neoplasm in six patients., Methods: Clinical data available were collected. Serial sections and immunohistochemical (IHC) analysis for CK17 and human papilloma virus (HPV) were performed on available materials., Results: Five of the six patients were males. Mean age at diagnostic was 56 years. Lesions were localized on the face and scalp in four of six patients. The lesions associated with TB were inverted follicular keratosis (IFK) in three cases, seborrhoeic keratosis (SK) in two cases and IFK with verruca vulgaris pattern in one case. IHC for HPV was negative in the four cases tested. Staining for CK17 was always positive in TB. It was often positive in the associated neoplasm., Conclusion: TB can be associated with benign epidermal/follicular neoplasm in composite tumors. The association of TB and IFK with direct connection between the lesions is another argument in favor of the follicular origin of IFK. TB can be added to the spectrum of SK-associated tumors. Battistella M, Peltre B, Cribier B. Composite tumors associating trichoblastoma and benign epidermal/follicular neoplasm: another proof of the follicular nature of inverted follicular keratosis.