Rare Cutaneous Malignancy Research Articles

An Internally Validated Prognostic Risk-Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined. Patients from six centers (2005-2020) with clinical stage I-II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables. Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%. A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials.

Yield of sentinel lymph node biopsy in sebaceous carcinoma and predictors of advanced disease: A retrospective analysis of the National Cancer Database

To the Editor: Sebaceous carcinoma (SC) is a rare cutaneous malignancy with potential for lymph node or distant metastasis. Most SC presents as localized disease, but periocular SC manifests distinct tumor behavior from extraocular SC with a greater propensity for metastasis. Present guidelines suggest that American Joint Committee on Cancer, Eighth Edition stage T2c periocular or greater tumors can be considered for sentinel lymph node biopsy (SLNB), although SLNB is not recommended for extraocular SC because subclinical nodal metastasis is thought to be uncommon in this setting.

Marjolin's ulcer: A case report of a rare but preventable lesion

Marjolin's ulcer (MU) is a rare cutaneous malignancy first described in 1828. MU arises in the setting of injured skin with subsequent chronic scarring or ulceration and eventual malignant transformation. While most cases of MU are associated with burn scars, less common settings have included traumatic wounds, venous stasis ulcers, osteomyelitis and pressure sores. MU may develop at any age but tends to affect older individuals. This is likely due to the typically long latency period from inciting event to malignant transformation, which averages 30 to 35 years. A male predilection exists. Lesions occur at any anatomic site, but the lower extremities and the head and neck region are most frequently affected. The predominant malignancy in MU is squamous cell carcinoma (8090%) followed by cases of basal cell carcinoma and malignant melanoma. The treatment of choice is wide surgical resection. MU is typically an aggressive malignancy with a high recurrence rate and poor 5-year survival. A 70 year-old woman from Togo had suffered a burn injury to the left side of her head many years previously. The wounded skin remained unchanged for decades, but recently developed an enlarging ulcer. Incisional biopsy of the ulcerated tissue resulted in a final diagnosis of keratinizing squamous cell carcinoma. Given the clinical setting, the lesion was deemed consistent with a MU. MU is thought to be a largely preventable form of cutaneous malignancy. Proper wound management, including efforts to minimize infection and healing by secondary intention, substantially reduces the risk of malignant transformation. For this reason, MU has a propensity to affect disadvantaged individuals living in poverty who have limited access to proper or adequate healthcare.

Rare Cutaneous Malignancies in Skin of Color.

There is a scarcity of information regarding the clinical characteristics of rare cutaneous malignancies in skin of color that has yet to be comprehensively explored. To review and compile the racial differences in epidemiology, clinical presentation, histology, treatments, and outcomes of 3 rare skin cancers: dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). Several searches with keywords denoting specific skin cancer type and race were conducted on PubMed to complete this narrative review. We analyzed 50 sources that were relevant to the initial objective. The literature demonstrates that there are nuances in DFSP, MCC, and SC unique to African Americans, Asians/Pacific Islanders, and Hispanics that may differ significantly from Caucasian counterparts. African Americans consistently suffer from the worst clinical outcomes in all 3 rare cutaneous malignancies reviewed. Greater physician awareness and knowledge of the discussed racial differences is the preliminary step to address these disparities.

Recurrence of metastatic Merkel carcinoma after cessation of avelumab in a patient previously with a complete response

AbstractBackgroundMerkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine malignancy. Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with metastatic MCC (mMCC). In mMCC, the response duration after cessation of ICIs treatment for complete response (CR) is unknown.ObservationWe report a case of a woman in her 70s with metastatic MCC treated in first‐line with avelumab. The treatment was stopped after 2 years of CR. The patient relapsed after 11 months of cessation of treatment and rechallenge with avelumab at the same dosing regimen was decided. The first tumour assessment at 3 months after reintroduction revealed a CR.DiscussionIn contrast with observations made for patients who have discontinued ICIs in the metastatic melanoma setting, disease progression is observed after ICIs cessation in mMCC including for patients with low tumour burden and who achieve a CR.ConclusionThe case of our patient underlines this risk of relapse and suggests great caution before stopping ICIs in patients treated for mMCC, even when they are in CR.

Advances in Immunology: A Cornerstone in Diagnosis and Therapy of Merkel Cell Carcinoma.

Merkel cell cancer (MCC) is a rare cutaneous malignancy arising from neuroendocrine cells. This rare but lethal malignancy (mortality greater than 30%) has also tripled in incidence over the last two decades. The role of immunodeficiency in pathogenesis of this rare malignancy is well established, with elucidation of viral pathogenesis by Merkel cell polyoma virus (MCPyV), a novel polyoma virus, in a majority of patients. Viral neoantigens while playing an important role in oncogenesis can also aid in early immunologic detection of recurrent disease. Viral neoantigens can also be targets for immunotherapy. Immune checkpoint inhibitors (ICI) have established role in frontline therapy in addition to recurrence of metastatic MCC. ICI therapy is being explored in adjuvant and neoadjuvant settings as well. We would like to illustrate curative potential of early diagnosis of recurrence and prompt use of ICI in treatment of oligometastatic disease in our case presentation.

A case series of rare cutaneous malignancies

Cutaneous malignancies are rare in people with darker skin types compared to fair skin. Cutaneous malignancies differ according to their origin. Squamous and basal cell carcinomas are by far the most common malignancies. Other types of malignancies are rarer. We report 3 cases of rarer cutaneous malignancies.

Primary Cutaneous Gamma-Delta T Cell Lymphomas: A Case Series and Overview of the Literature.

Primary cutaneous gamma-delta T cell lymphomas (PCGDTCLs) are rare and aggressive cutaneous malignancies that have been diagnostically challenging for dermopathologists and clinicians since their first published descriptions in 1991. Since then, the availability of immunostaining for T cell receptors γ and δ in formalin-fixed paraffin-embedded samples has greatly increased our knowledge of the gamma-delta phenotype by showing that it may also be present in the context of indolent entities, such as mycosis fungoides (MFs) and lymphomatoid papulosis, and this has raised questions concerning its diagnostic and prognostic implications. We here describe the histological and clinical differences between the dermo-epidermal and subcutaneous sub-groups of PCGDTCL observed in a cohort of 20 patients attending a single experienced centre, with particular focus on cases with an MF-like presentation, which are still less well defined than those of classic MF.

Evaluation of in vivo reflectance confocal microscopy in the diagnosis of extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that most commonly affects the apocrine glands of older men and women. Because it is associated with other cancers, early diagnosis and evaluation are needed. This study is to evaluate the value of reflectance confocal microscopy (RCM) in diagnosing EMPD. A total of 73 patients with clinically suspicious diagnosis of EMPD were enrolled in this study, and the RCM device imaged their lesions. Moreover, 67 patients underwent skin biopsies to confirm the diagnosis. We retrospectively analyzed the results of RCM and histological diagnosis and then evaluated the RCM value of biopsy-confirmed lesions. Based on the RCM image analysis, 54 of 73 (74.0%) patients were diagnosed with EMPD. Of all 67 biopsied lesions, 52 (77.6%) were EMPD. Then, we analyzed the RCM characteristics of 52 cases of biopsy-confirmed EMPD, compared their RCM image characteristics of three different lesions of EMPD, and further concluded the key points of EMPD under RCM microscopy based on the 52 EMPD cases. Finally, we focused on the differential diagnosis of EMPD from other skin diseases. RCM showed great diagnostic value in diagnosing EMPD.

Primary mucinous adenocarcinoma of the eyelid: A case with initial clinical misdiagnosis requiring surgical re-excision of the tumor.

Introduction and importancePrimary mucinous adenocarcinoma (PMA) of the skin is a rare condition that is usually seen in elderly patients, most commonly involves the periorbital region as a slow growing mass. Histopathological and immunohistochemical (IHC) stains are of paramount importance for the diagnosis of these lesions, which are usually misdiagnosed either as benign or metastatic mucinous adenocarcinomas.Case presentationWe herein report a rare presentation of PMA in a 70-year-old male patient who presented with an upper eyelid residual lesion after being incompletely excised elsewhere as an epidermal cyst and was successfully managed by complete surgical excision with frozen section control of the margins and no evidence of recurrence.DiscussionPMA is a rare sweat gland malignancy that involves the eyelid in 41.9% in the head and neck area and is a disease of the elderly with median age of 60 years and variable reported racial and gender predilection. Diagnosis of PMA is challenging both clinically and histopathologically, which was the case in our patient's initial incomplete excision with the presumed diagnosis of a benign epidermal cyst. Proper final tissue diagnosis and surgical management in our patient ensured his favorable outcome.ConclusionAccurate diagnosis of PMA requires a high index of clinical suspicion and accurate histopathological diagnosis aided by proper IHC markers.

Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cutaneous malignancy with poor prognosis. In Europe, approved systemic therapies are limited to the PD-L1 inhibitor avelumab. For avelumab-refractory patients, efficient and safe treatment options are lacking.MethodsAt three different sites in Germany, clinical and molecular data of patients with metastatic MCC being refractory to the PD-L1 inhibitor avelumab and who were later on treated with combined IPI/NIVO were retrospectively collected and evaluated.ResultsFive patients treated at three different academic sites in Germany were enrolled. Three out of five patients investigated for this report responded to combined IPI/NIVO according to RECIST 1.1. Combined immunotherapy was well tolerated without any grade II or III immune-related adverse events. Two out of three responders to IPI/NIVO received platinum-based chemotherapy in between avelumab and combined immunotherapy.ConclusionIn this small retrospective study, we observed a high response rate and durable responses to subsequent combined immunotherapy with IPI/NIVO in avelumab-refractory metastatic MCC patients. In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC.

S3057 Upper Gastrointestinal Bleeding Secondary to Gastric Metastasis of Pleomorphic Dermal Sarcoma

INTRODUCTION: Pleomorphic dermal sarcoma (PDS) is a rare cutaneous malignancy, seen primarily in sun exposed areas of elderly individuals. Along with atypical fibroxanthoma (AFX), it is believed to belong to a spectrum of malignant disorders arising from a similar fibrohistiocytic mesenchymal origin. Compared to AFX, PDS represents a more aggressive phenotype of disease with higher rates of recurrence and metastasis. CASE DESCRIPTION/METHODS: An 87-year-old male with a history PDS of the scalp with metastasis to the right humerus presented to the hospital with one week of melena. Pertinent past medical history included non-small cell lung cancer, chronic lymphocytic leukemia, melanoma, squamous and basal cell carcinoma of the skin. On presentation he was noted to be anemic with a hemoglobin of 6.8 g/dL and hematocrit of 22%. He was started on intravenous (IV) proton pump inhibitor (PPI) and underwent an esophagogastroduodenoscopy (EGD). Upon visualization of the stomach, four masses were identified along the greater curvature ranging between 1cm and 2.5cm in size, three of which were actively bleeding. Biopsies of these masses were obtained with cold biopsy forceps. No alternative source of bleeding was identified on exam. Following EGD, supportive measures were continued with IV PPI and packed RBC transfusions. Tissue histology of the gastric masses were consistent with a malignant spindle cell neoplasm, identical to that of the patient's known PDS. Additional imaging revealed new soft tissue lesions in the left hepatic lobe, right kidney, bladder and peritoneum. Given his diffusely metastatic disease, co-morbidities and frailty, therapeutic options were limited. He was deemed not an appropriate chemotherapy candidate and ultimately pursued hospice care. DISCUSSION: We present a case of upper gastrointestinal bleeding secondary to gastric metastasis of PDS. Metastasis occurs in approximately 10-20% of patients with PDS, most commonly involving the lungs and skin1. PDS had previously been classified as undifferentiated pleomorphic sarcoma or malignant fibrous histiocytoma. Under this nomenclature it has rarely been described to metastasize to the stomach and few cases have presented with gastrointestinal bleeding. This case contributes to the general understanding that the stomach can be a metastatic site for a wide variety of non-gastrointestinal cancers.Figure 1.: Proximal gastric body mass along the greater curvature.Figure 2.: Distal gastric body mass along the greater curvature.

Clinical Characteristics, Treatment, and Prognostic Factors of Patients With Primary Extramammary Paget's Disease (EMPD): A Retrospective Analysis of 44 Patients From a Single Center and an Analysis of Data From the Surveillance, Epidemiology, and End Results (SEER) Database.

Objective: Primary extramammary Paget's disease (EMPD) is a rare cutaneous malignancy. The aim of this article is to analyze clinical characteristics, evidence of the prognosis, and share treatment experience of primary EMPD.Methods: We extracted 771 patients' data from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2013 to investigate the characteristics and prognosis of patients with EMPD. In addition, 44 patients with primary EMPD in our hospital were retrospectively reviewed for 10 years.Results: Compared with patients younger than 65 years, patients diagnosed at 65–74 years [hazard ratio (HR), 2.453] and 75 years or older (HR, 5.750) had shorter survival. Patients with a primary site in the truncal skin (HR, 0.367) or scrotum (HR, 0.246) had better survival compared to those with a primary site in the perianal area. Compared with localized EMPD, EMPD with distant (HR, 18.821) and regional (HR, 2.180) metastases was associated with a worse prognosis. Patients who received radiotherapy had decreased survival, with an HR of 2.039. Patients with a higher N stage, M stage, and American Joint Committee on Cancer (AJCC) stage had a decreased prognosis (p < 0.001).Conclusions: Older age at diagnosis, primary site in the perianal area, distant metastasis, radiotherapy, and higher N stage, M stage, and AJCC stage may result in decreased survival.

Primary cutaneous adenoid cystic carcinoma: Characterizing US demographics, clinical course, and prognostic factors

To the Editor: Primary cutaneous adenoid cystic carcinoma (PCACC) is a rare primary cutaneous malignancy, first described by Boggio1 in 1975. Histologically, PCACC presents with basophilic cells having adenoid or cribriform patterns due to true lumina within islands that are surrounded by modified myoepithelial cells and prominent basement membrane material.2,3 Given the somewhat conflicting data of indolent tumors as well as tumors with more aggressive behavior, we studied the incidence and survival patterns for patients with PCACC in the United States.

Distribution pattern of invasion-related bio-markers in head Marjolin's ulcer.

Marjolin's ulcer (MU) is a rare and aggressive cutaneous malignancy that typically presented in an area of traumatized or chronically inflamed skin and particularly in burn scars. Among them, the MU in the scalp with extensive invasion of the skull is exceptional and severe. The principle of management for MU is to obtain an early diagnosis and perform prompt surgical interventions. The invasive capacity of MU may vary among different sites of the scalp, which may require different therapeutic strategies for surgical excision. However, no clear evidence has been provided to determine the invasion ability of MU at different regions of the lesion as a surgical guidance. In present study, a 41-year-old female with a 40-year history of scalp ulceration has been examined. After resection of the MU lesion, hematoxylin and eosin (H&E) staining was performed to confirm the pathology of the cutaneous malignancy after surgical excision. Furthermore, reverse transcription-quantitative PCR experiment was performed out to determine the expression levels of invasion-associated biomarkers at different sites of the scalp affected by MU. Pathological analysis with H&E staining indicated a differentiated squamous cell carcinoma with invasion of the skull. The invasion-associated biomarkers were highly expressed in the core region compared to the middle region as well as the edge of MU tissue. Taken together, the present study suggests that the expression pattern of invasion-associated biomarkers varies between different regions of the MU lesion. High expression levels in the core region of MU indicates that the resection of the center area may be critical for the successful surgical treatment of MU.

Merkel Cell Polyomavirus and Merkel Cell Carcinoma.

Viruses are the cause of approximately 15% of all human cancers. Both RNA and DNA human tumor viruses have been identified, with Merkel cell polyomavirus being the most recent one to be linked to cancer. This virus is associated with about 80% of Merkel cell carcinomas, a rare, but aggressive cutaneous malignancy. Despite its name, the cells of origin of this tumor may not be Merkel cells. This review provides an update on the structure and life cycle, cell tropism and epidemiology of the virus and its oncogenic properties. Putative strategies to prevent viral infection or treat virus-positive Merkel cell carcinoma patients are discussed.

Management of pleomorphic dermal sarcoma.

Pleomorphic dermal sarcoma (PDS) is a rare, poorly defined skin neoplasm with features similar to atypical fibroxanthoma, but with adverse histopathological characteristics indicating metastatic potential such as tumour necrosis, invasion beyond superficial subcutis or vascular and/or perineural infiltration. Optimal treatment for PDS is uncertain and reported outcomes vary due to the rarity of this diagnosis and uncertainty over histopathological categorization. The aim of this study was to review the clinical and histopathological features of PDS in a single Australian centre. A retrospective review of all patients managed at the Peter MacCallum Cancer Centre with PDS between 2003 and 2017 was performed by a search of electronic records and histories reviewed. A total of 27 patients were identified, mostly elderly males (85.2%, mean age 79.8 years). Lesions were seen most commonly on the head and neck region (96.3%), predominantly on the scalp (63%). Mean tumour radial surgical excision margin was 12.8 mm. Eighteen patients (66.7%) underwent radiotherapy; 13 adjuvant, three neoadjuvant and two with palliative intent. After median follow-up of 46.4 months, two patients had recurrence (7.4%); both had inadequate deep margins at first excision. There were three all-cause deaths in the cohort. There was one disease-specific mortality with metastatic PDS disease at the time of initial presentation. PDS is a rare cutaneous malignancy most commonly found in the head and neck region in elderly men, which is best managed with adequate surgical excision. The role of radiotherapy is undefined and an area for future investigation.

Maladie de Paget extra-mammaire : corrélation dermatopathologie-dermatoscopie

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that can be easily confused with other diseases due to its diverse clinical manifestations, delaying the timing of treatment. Therefore, early diagnosis is extremely important. It has been reported that dermoscopy can be used to evaluate superficial skin tumors.To investigate the dermoscopic characteristics of EMPD diagnosed by histopathology and to develop a decision tree model that can provide clinicians with a reference to facilitate early diagnosis.All patients were evaluated by dermoscopic and histopathologic examinations. Dermoscopic images were assessed, and a decision tree model was constructed using SPSS (version 25.0).A total of 49 patients were included in this study. We found that EMPD was most likely to be misdiagnosed when the disease duration was less than 2.5 years. Porcelain-white patches were the only key clinical feature other varying dermoscopic features could not be differentiated from those of EMPD-mimicking diseases. Polymorphic vessels were considered to be significant when the duration of the disease ranged from 0.1 year to 2.5 years. However, when the duration was >2.5 years, present (or absent) glomerular vessels were all considered EMPD.Dermoscopy can be used as an auxiliary diagnostic tool for the diagnosis and management of EMPD. The decision tree can guide clinical diagnosis further validation studies are necessary due to the limited number of cases.

Extraocular sebaceous carcinoma as a rapidly growing back mass: a case report

Sebaceous carcinoma is a rare cutaneous malignancy that frequently mimics other dermatologic conditions. Extraocular subtypes are uncommon, but when present are frequently located in the head and neck region. Herein, we present a patient with a rapidly growing upper back mass eventually diagnosed as sebaceous carcinoma and managed with wide surgical excision. Currently, sparse literature exists to guide management of such patients. This case highlights not only the diagnostic challenges of sebaceous carcinoma, but also the need for further studies to investigate therapeutic interventions and long-term outcomes.

Merkel cell carcinoma- A retrospective case series

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. Excessive exposure to sunlight and ultraviolet (UV) radiation, immune suppression and advanced age are the major risk factors for MCC. It typically presents in the head and neck region (50%), followed by extremities (40%) and rarely at other sites (