Cutaneous Merkel Cell Carcinoma Research Articles

Different prognosis in cutaneous early-onset and late-onset Merkel cell carcinoma: a population-based retrospective study.

Merkel cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer. However, there is limited research on the clinicopathological features of early-onset MCC (EOMCC) and the differences between EOMCC and late-onset MCC (LOMCC). Our objective was to evaluate the clinicopathological features and cancer-specific survival (CSS) of EOMCC. Our cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2018, to December 31, 2020. Data from 1941 patients who were diagnosed with primary cutaneous MCC were included. We then divided the patients with MCC into two groups: those with EOMCC (526 patients) and those with LOMCC (1415 patients). CSS is used as the primary outcome. The EOMCC group exhibited trends toward advanced tumor progression, an expanded surgical scope, increased lymph node retrieval, intensified radiotherapy, greater utilization of systemic therapy, and a better prognosis. Multivariate analysis revealed that LOMCC (HR 3.305 [2.002-5.456], P < 0.001), advanced T stage (HR 1.430 [1.139-1.797], P = 0.002), advanced N stage (HR 1.522 [1.221-1.897], P < 0.001), M1 stage (HR 2.587 [1.480-4.521], P < 0.001), and radiation (HR 0.586 [0.410-0.837], P = 0.003) were significantly associated with CSS. Among these factors, EOMCC/LOMCC was most strongly associated with CSS, indicating that LOMCC is an independent risk factor for CSS. Interestingly, we found that regional EOMCC and localized or in situ LOMCC had almost completely overlapping survival curves (Plog-rank = 0.620). Additionally, we observed that the TNM staging + age model was a more accurate predictor of CSS among MCC patients than using TNM staging alone. We found that EOMCC has distinct clinicopathological features compared to LOMCC. EOMCC is associated with better CSS. The combination of TNM staging and age was more accurate for predicting patient outcomes than TNM staging alone.

No difference in overall survival for primary cutaneous Merkel cell carcinoma after Mohs micrographic surgery and wide local excision: A multicenter cohort analysis

No difference in overall survival for primary cutaneous Merkel cell carcinoma after Mohs micrographic surgery and wide local excision: A multicenter cohort analysis

No difference in survival for primary cutaneous Merkel cell carcinoma after Mohs micrographic surgery and wide local excision

The preferred treatment for clinically node-negative Merkel cell carcinoma (MCC) is surgical excision in conjunction with sentinel lymph node biopsy. There is limited large-scale research on survival outcomes by surgical approach for management of the primary tumor. To compare overall and MCC-specific survival outcomes in clinically and pathologically node-negative MCC patients treated with wide-local excision (WLE) and Mohs micrographic surgery (MMS) in a nationally representative sample. Overall and MCC-specific survival outcomes for primary MCC tumors contained in the SEER-18 database from 1989 to 2015 were stratified by surgical modality and analyzed via competing risk analysis. A total of 2,359 US adults with MCC were included in the analysis. For overall and MCC-specific survival, there was no significant difference in survival outcomes between WLE and MMS on multivariable analysis ((HR 1.04 [95% CI 0.88 - 1.22]; SHR 0.76 [95% CI 0.53 - 1.09]). Sentinel lymph node biopsy (SLNB) was associated with improved overall survival and MCC-specific survival. Retrospective design of SEER and the lack of covariates such as comorbidities and immunostaining. There is no survival disadvantage for MMS compared to WLE as the surgical modality for primary cutaneous MCC. SLNB should be coordinated prior to MMS.

Prevalence of Merkel Cell Polyomavirus in Primary Eyelid Merkel Cell Carcinomas and Association With Clinicopathological Features

Merkel cell polyomavirus (MCPyV) infection is a known to be a critical risk factor for the development of Merkel cell carcinoma (MCC). Various reports on cutaneous MCC have shown that the differences in clinicohistopathological characteristics depend on the presence of MCPyV, but the situation in eyelid MCC is unknown. This study aimed to assess the prevalence of MCPyV in patients with eyelid MCC and examine the clinicohistopathological characteristics of MCPyV-associated eyelid MCC. Retrospective observational case series with laboratory investigations. Ten patients treated for eyelid MCC were included. Histopathological characteristics were examined by immunohistochemical staining using 12 antibodies. MCPyV infection was evaluated by PCR using primer sets targeting large T antigens of the MCPyV genome and by immunohistochemical staining using CM2B4 and Ab3 monoclonal antibodies. The MCPyV viral load was also quantified by PCR using 3 primer sets. All patients (4 males and 6 females) were Japanese with mean age of 79 (range: 63 to 87) years. One patient died due to distant metastasis 8 months after surgery for MCC. Immunohistochemical studies showed typical MCC findings in all cases, including CK20 and neuroendocrine marker positivity. PCR and immunohistochemistry with CM2B4 and Ab3 detected MCPyV antigen in all tumors. Quantitative PCR using sT, LT4, and TAg primers yielded 0.94, 1.72, and 1.05 copies per cell, respectively. Clinical and histopathological characteristics of 10 patients with eyelid MCC were elucidated. MCPyV infection was detected in all eyelids. These results provide insight for understanding the tumorigenesis of eyelid MCC.

Intradural extramedullary cervical metastasis from Merkel cell carcinoma: a case report and literature review

BackgroundMerkel cell carcinoma (MCC) is a rare aggressive primary skin carcinoma with an incidence of 44 cases per 100,000.The natural course of MCC often results in rapid growth and early metastasis. On the other hand, the spinal cord is rarely affected and frequently features the end stage of the disease. The aim of this paper was to clarify the management of patients with spine metastasis from a skin lesion and showed a case-based update.Case presentationA 73-year-old female was admitted to the Neurosurgical Department in December 2021 for a sudden right hemiparesis with bladder dysfunction and a history of cutaneous Merkel cell carcinoma. A magnetic resonance imaging (MRI) of the central nervous system (CNS) showed an intradural-extramedullary right-sided C6–C7 tumor with mass effect and edema of the cervical cord. The patient underwent a C6–C7 laminectomy with microsurgical total resection of the intradural extramedullary lesion. The neuropathological examination identified a metastasis from Merkel cell carcinoma. Nowadays, evidence for spinal metastasis from malignities skin cancer is generally lacking, probably because they are extremely rare. The exact time of life expectancy is controversial, and some clinicians use a cutoff of 3 months to determine whether surgical intervention should be offered, while others advocate at least 6 months of life expectancy.ConclusionsTo the best of our knowledge, we showed the first case of solitary intradural extramedullary cervical spine metastasis from MCC. We recommend to consider metastasis of MCC in the differential diagnosis of spinal metastasis.

A web-based predictive model for overall survival of patients with cutaneous Merkel cell carcinoma: A population-based study.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma with a high mortality rate, so it is necessary to create models to predict overall survival of MCC. We developed an easy-to-use web-based calculator to predict the OS of MCC patients based on the nomogram. MCC patients between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to training and validation cohorts. Patients between 2016-2017 serve as the external validation cohort. Relevant risk factors were identified by univariate and multivariate COX hazards regression methods and combined to produce nomograms. The concordance index (C-index), area under the receiver operating characteristic (AUC) curve, and calibration plots have demonstrated the predictive power of the nomograms. Decision curve analysis (DCA) was used to measure nomograms in clinical practice. Patients were divided into three groups according to the scores of the nomogram. A total of 3480 patients were randomly assigned to the training group and validation group in this study. Meaningful prognostic factors were applied to the establishment of nomograms. The C-index for OS was 0.725 (95% CI: 0.706-0.741) in the training cohort and 0.710 (95% CI: 0.683-0.737) in the validation cohort. In the external validation cohort, C-index was 0.763 (95% CI: 0.734-0.792). The C-index of training cohort, validation cohort and external validation cohort for CSS were 0.743 (95% CI:0.725-0.761), 0.739(95%CI:0.712-0.766) and 0.774 (95%CI:0.735-0.813), respectively. The AUC and calibration plots of 1-, 3-, and 5-year OS rates showed that the nomogram had good predictive power. DCA demonstrated that the nomogram constructed in this study could provide a clinical net benefit. Our calculator demonstrated excellent predictive capabilities for better risk grouping of MCC patients. We created novel nomograms of prognostic factors for MCC, which more accurately and comprehensively predicted 1-, 3-, and 5-year OS/CSS in MCC patients. We established a calculator which can easily and quickly calculate the risk grouping of MCC patients by inputting clinically relevant characteristics. This can help clinicians identify high-risk patients as early as possible, carry out personalized treatment, follow-up, and monitoring, and improve the survival rate of MCC patients.

S3551 Gastric Metastasis of Merkel Cell Carcinoma: A Rare Cancer

Introduction: Merkel Cell Carcinoma (MCC) is a rare aggressive cutaneous neuroendocrine carcinoma. MCC is localized in 65% of cases, 26% cases spread to lymph nodes and metastasis is seen in 8% of cases. Stomach metastasis is rare site of metastasis, seen in 0.2 to 0.7% of cases on autopsy. CK 20 is a sensitive and specific marker of MCC. We present a case of a 63-year-old man who presented with chronic anemia and was found to have gastric metastasis of his cutaneous Merkel Cell Carcinoma. Case Description/Methods: A 63-year Caucasian man with pertinent history for hypertension, chronic anemia on iron therapy and stage IV neuroendocrine cutaneous tumor of left thigh with distant metastasis on treatment presented with melena, worsening fatigue, and shortness of breath for 2 weeks. Two months prior to this hospitalization, the patient was admitted for symptomatic anemia where patient had undergone Upper Gastrointestinal (UGI) Endoscopy. It had revealed non-bleeding gastric ulcers with pigmented material and biopsy was negative for malignancy (Figure a). On presentation his labs were significant for hemoglobin/hematocrit of 5.2/14.7% (g/dL/%). Computed Tomography Angiogram of abdomen and pelvis revealed a GI bleeding source within the proximal stomach. UGI endoscopy was performed after adequate resuscitation which revealed a large, fungating, infiltrative and ulcerated masses in the body of the stomach (Figure b). Biopsies showed malignant cells with immunohistochemical staining positive for chromogranin, synaptophysin, CK7, and CK20. It was reported that the immunomorphological features of initial biopsy of left posterior thigh were like this gastric biopsy. It was concluded that the patient's gastric mass was metastatic MCC. Discussion: MCC is a rare extremely aggressive carcinoma. Its spread to stomach is rare but should be considered in patients with cutaneous neuroendocrine tumor who present with iron deficiency anemia/GI bleeding. In addition, gastric metastasis is exponentially aggressive. Our patient’s gastric ulcer with negative biopsy grew into a fungating mass with proven MCC in two months. Thus, we would also like to highlight the importance of re-biopsy when the index of suspicion is high. Our patient’s initial biopsies were negative for malignancy while subsequent biopsies showed MCC. A combination surgical excision and loco-regional radiotherapy is used for treatment of aggressive primary MCC without distant metastasis. Radiotherapy, or combination with chemotherapy can be used for unresectable MCC.Figure 1.: (a) Initial UGI endoscopy done 2 months before the presentation. Shown above is gastric ulcer with pigmentation in Gastric body and Fundus (b) A large, fungating, infiltrative and ulcerated mass with no bleeding at gastric body. Biopsy of this mass showed MCC.

SATB2 is expressed in neuroendocrine carcinoma of the uterine cervix.

Neuroendocrine carcinoma (NEC) of the uterine cervix is less characterized than neuroendocrine neoplasms of other sites such as of the digestive system and the lung. Special AT-rich sequence-binding protein 2 (SATB2) recently emerged as a marker of well-differentiated neuroendocrine tumors of the lower gastrointestinal (GI) tract. Among NECs, SATB2 is more frequently expressed in cutaneous Merkel cell carcinoma than in NEC of other anatomical sites. In our study, we performed an immunohistochemical study of SATB2 in 16 NECs of the uterine cervix, where the expression of these markers is still undefined. SATB2 was expressed in 12/16 cervical NECs (75%), with 7/16 cases (44%) showing SATB2 positivity in ≥ 50% of cells. In 7 cervical NECs associated with a non-neuroendocrine component, the expression of SATB2 was restricted to the neuroendocrine component. SATB2 was positive in all cases that expressed CDX2 (n = 7) and TTF1 (n = 5), with no evident association with p16 and p53. Our study demonstrated that SATB2 is often expressed in NECs of the uterine cervix. This information should be taken into account when assessing the origin of a NEC.

Evaluation of clinical characteristics and pre-biopsy impressions of primary Merkel cell carcinoma of the skin.

Merkel cell carcinoma is an aggressive carcinoma of the skin notable for protean presentation on physical exam. A retrospective cohort of 232 patients with primary cutaneous Merkel cell carcinoma was reviewed for availability of data on pre-biopsy clinical differential diagnosis based on clinical exam. Data was available for 192 patients (83%). The three most common impressions were cyst (33.3%), basal cell carcinoma (31.8%), and squamous cell carcinoma (19.8%). Merkel cell carcinoma was correctly suspected in only 13 cases (6.8%). A greater proportion of lesions that were less than or equal to 2 cm in diameter (10.2%) or carried BCC as a co-diagnosis (11.5%) were correctly suspected as Merkel cell carcinoma prior to biopsy, versus lesions greater than 2 cm in diameter (1.6%) or carrying SCC as a co-diagnosis (2.6%), suggesting that clinicians may be anchoring on the well-publicized concept of Merkel cell carcinoma as a small, pearly papule in real-world practice.

Two Clinical Cases of Metastatic Merkel Cell Carcinoma Illustrating Avelumab Tolerability in Elderly Patients

AbstractWe present two cases of primary cutaneous Merkel cell carcinoma in a 80-year and a 95-year old patient. Both patients had a wide local excision, but early recurrences occurred. Case 1 required palliative radiotherapy. He did not receive chemotherapy but case 2 did. They then proceeded to have immunotherapy with sustained responses lasting greater than 2 and 3 years. This report highlights an important new class of drug for the treatment of advanced Merkel cell carcinoma. Furthermore, our case report demonstrates that avelumab immunotherapy can be safely delivered to elderly patients, including 80- and 95-year-old patients. This report parallels the high and durable response rates to avelumab (including complete responses) that were shown in the JAVELIN phase II trials.

An Uncommon Case of Colonic Neuroendocrine Carcinoma with Scalp Metastasis

Abstract Introduction/Objective Neuroendocrine neoplasms of the colon account for &amp;lt;1% of all colorectal malignancies. While visceral metastasis of neuroendocrine neoplasms is commonly observed, cutaneous distant metastasis has infrequently been reported and correlates with an advance stage and progression of disease. To our knowledge, there have been only 10 cases of neuroendocrine neoplasms with metastasis to the scalp reported in the literature. Herein, we report an unusual case of colonic neuroendocrine carcinoma with scalp metastasis, that can be microscopically indistinguishable from the highly aggressive cutaneous neuroendocrine carcinoma, Merkel Cell Carcinoma. Methods/Case Report A 47-year-old female with a history of ileocecal neuroendocrine carcinoma and status post right hemicolectomy had developed liver metastasis and subsequently had an orthotopic liver transplant. PET scan later revealed multiple areas of increased activity involving the ribs, scalp and cervical lymph node that were concerning for malignancy. The scalp lesion consisted of a 7mm non-tender, mobile, violaceous, erythematous dermal nodule that was clinically concerning for cutaneous metastasis. A skin punch biopsy microscopically revealed a subcutaneous infiltrate of nests composed of neoplastic monotonous blue cells with the classic nuclear “salt and pepper” chromatin and scant eosinophilic cytoplasm. The lesional cells showed positive immunoreactivity for synaptophysin and chromogranin. With the given patient’s clinical history and presentation, the observed histological findings and immunophenotypic expression of the tumor cells supported a diagnosis of metastatic neuroendocrine carcinoma. Results (if a Case Study enter NA) N/A Conclusion Metastatic neuroendocrine carcinoma to the scalp is a rare entity and is infrequently encountered in dermatopathology. Given the location and the gross appearance of the scalp lesion, a wide differential diagnosis would include both benign and malignant tumors. In particular, Merkel Cell Carcinoma can grossly and histologically mimic metastatic colonic neuroendocrine carcinoma. Both entities would show synaptophysin and chromogranin uptake. However, metastatic tumors originating from the colon will demontrate CDX2 and SATB2 nuclear staining. We share this rare case of metastatic colonic neuroendocrine carcinoma as it is an important differential diagnosis for primary cutaneous Merkel Cell Carcinoma.

Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas.

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

Merkel Cell Carcinoma of Unknown Primary: Immunohistochemical and Molecular Analyses Reveal Distinct UV-Signature/MCPyV-Negative and High Immunogenicity/MCPyV-Positive Profiles.

Simple SummaryMerkel cell carcinomas (MCCs) of unknown primary are defined as deep-seated tumors without an associated cutaneous tumor. Although the distinction has important clinical implications, it remains unclear whether these tumors represent primary tumors of lymph nodes or metastatic cutaneous primaries. We compared the immunohistochemical profiles of four groups of Merkel cell carcinomas (virus-positive and virus-negative unknown primary tumors and virus-positive and virus-negative cutaneous tumors) and performed molecular studies on the unknown primary tumors. Virus-positive and virus-negative Merkel cell carcinomas of unknown primary (MCC-UPs) exhibited an immunoprofile similar to virus-positive and virus-negative primary cutaneous MCCs, respectively. Similar to primary cutaneous Merkel cell carcinomas, virus-negative unknown primary tumors exhibited UV signatures and frequent high tumor mutational burdens, whereas few molecular alterations were noted in virus-positive tumors. Although additional studies are warranted for the virus-positive cases, our findings are supportive of a cutaneous metastatic origin for virus-negative Merkel cell carcinomas of unknown primary.Background: Merkel cell carcinomas of unknown primary (MCC-UPs) are defined as deep-seated tumors without an associated cutaneous tumor. Although the distinction has important clinical implications, it remains unclear whether these tumors represent primary tumors of lymph nodes or metastatic cutaneous primaries. Methods: We compared the immunohistochemical profiles of four groups of MCCs (Merkel cell polyomavirus (MCPyV)-positive UP, MCPyV-negative UP, MCPyV-positive known primary (KP), and MCPyV-negative KP) using B-cell and pre-B-cell markers, cell cycle regulating proteins, follicular stem cell markers, and immune markers, and performed next generation and Sanger sequencing. Results: Virus-positive and virus-negative MCC-UPs exhibited an immunoprofile similar to virus-positive and virus-negative primary cutaneous MCCs, respectively. MCC-UP tumors (both virus-positive and -negative) were immunogenic with similar or even higher tumoral PD-L1 expression and intratumoral CD8 and FoxP3 infiltrates in comparison to MCPyV-positive cutaneous tumors. In addition, similar to primary cutaneous MCCs, MCPyV-negative MCC-UPs exhibited UV signatures and frequent high tumor mutational burdens, whereas few molecular alterations were noted in MCPyV-positive MCC-UPs. Conclusions: Our results showed distinct UV-signatures in MCPyV-negative tumors and high immunogenicity in MCPyV-positive tumors. Although additional studies are warranted for the MCPyV-positive cases, our findings are supportive of a cutaneous metastatic origin for MCPyV-negative MCC-UP tumors.

Morphologic Diversity of Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of unknown origin. We performed a retrospective histologic review of primary cutaneous MCCs diagnosed from 1997 to 2018 in several clinical institutions and literature review to determine the frequency of various unusual morphologic appearances of MCC. Of the 136 primary MCCs identified, intraepidermal carcinoma or epidermotropism was noted in 11/136 (8%) cases. An association with pilar cyst in 1/136 (0.7%) case, with actinic keratosis in 2/136 (1.5%) cases, with either invasive or in situ squamous cell carcinoma (SCC) in 14/136 (10%) cases, with poroma in 1/136 (0.7%), and with basal cell carcinoma in 1/136 (0.7%) case was noted. Trabecular pattern and rosettes were noted in 7/136 (5%) and 3/136 (2%) cases, respectively. There was one case of metastatic MCC in a lymph node with chronic lymphocytic leukemia and one rare case of metastatic MCC and SCC in a lymph node. Although uncommon, differentiation toward other cell lineage can be observed in both primary and metastatic MCCs. The tumor can assume a variety of histologic appearances including association with SCC, basal cell carcinoma, melanocytic neoplasm, and follicular cyst; as well as exhibit glandular, sarcomatous, and mesenchymal differentiation. This diversity of morphologic appearance of MCC reflects the complexity of its underlying pathogenesis.

Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma: expression of hypoxia-inducible factor-1α and its central downstream factors.

Metabolic reprogramming and altered gene expression mediated by hypoxia-inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia-inducible factor-1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options. To analyse the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (referred to as VEGF throughout the manuscript), VEGF receptor-2 (VEGFR-2), VEGF receptor-3 (VEGFR-3), glucose transporter-1 (Glut-1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC. The 16 paraffin-embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF-1α, VEGF, VEGFR-2 (KDR), VEGFR-3 (FLT4), Glut-1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2-10%; 3: 11-50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong). HIF-1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF-1α downstream factors Glut-1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR-2 were not expressed in tumour cells, whereas VEGFR-3 was expressed in all MCCs. HIF-1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36±2.41) than in McPyV- tumours (QS: 5.40±1.34; P=0.002). Similarly, VEGFR-3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00±2.52) than in McPyV- tumours (QS: 5.40±3.43, P=0.019). Our data provide first evidence for a role of HIF-1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV- tumours seem to show relevant differences.

皮肤Merkel细胞癌合并肺腺癌一例

皮肤Merkel细胞癌合并肺腺癌一例

TdT Expression Is a Marker of Better Survival in Merkel Cell Carcinoma, and Expression of B-Cell Markers Is Associated With Merkel Cell Polyomavirus.

Merkel cell carcinoma is a rare but very aggressive cutaneous tumor. We evaluated the prognostic potential of B-cell markers (terminal deoxynucleotidyl transferase [TdT], PAX5, CD117), follicular stem cell markers (CK15, CK19), p63, p53, RB, and Merkel cell polyomavirus (MCPyV; CM2B4) in 136 primary cutaneous Merkel cell carcinomas. Clinical, histopathologic, and immunohistochemical analyses were performed. The results were correlated with patient outcomes by Fisher exact test, log-rank tests, and Cox multivariate models. By Fisher exact test, although TdT significantly correlated with both lack of progression (P = .0087) and alive status (P = .0056), MCPyV status correlated only with alive status (P = .031). In univariate analyses, TdT, MCPyV, and RB significantly correlated with improved overall survival, whereas p63 and CK15 correlated with worse overall survival. However, in multivariate analyses, only TdT expression remained as an independent predictor of improved overall survival, Merkel cell carcinoma-specific survival, and progression-free survival. By linear regression analyses, significant correlations between MCPyV vs TdT, PAX5, and CD117 were observed. TdT expression is a potential marker of better survival in Merkel cell carcinoma. Expression of B-cell markers is associated with MCPyV, suggesting that clonal viral integration might play a role in the expression of these markers.

UV Signature Mutations Reclassify Salivary High-grade Neuroendocrine Carcinomas as Occult Metastatic Cutaneous Merkel Cell Carcinomas.

Salivary high-grade neuroendocrine carcinomas (NECs) are rare, occur predominantly in the parotid gland, and are difficult to differentiate from metastatic cutaneous Merkel cell carcinomas (MCCs), which have overlapping morphologic, immunophenotypic, and molecular profiles. Oncogenic Merkel cell polyomavirus (MCPyV), found in 70% to 80% of MCCs, has also been reported in a few salivary NECs, but this is controversial. A promising biomarker to distinguish the 2 tumor types are UV signature mutations. UV signature mutations indicate a sun damage-induced mechanism of pathogenesis and recently have been found to be highly prevalent in MCPyV-negative MCCs but would be inconsistent with salivary origin. Here, we examine UV signature mutations as a molecular marker to distinguish primary salivary high-grade NEC from MCC. Whole exome DNA sequencing was performed on matched tumor-normal tissue from 4 MCPyV-negative high-grade salivary NECs with no other primary source identified, as well as 3 melanomas and 3 lung NECs as positive and negative controls, respectively. UV signature mutations were found in all salivary NECs, when defined as ≥60% of total mutations being C-to-T transitions at dipyrimidine sites, and when compared with known human cancer-related mutational signatures. The presence of UV signature mutations in salivary high-grade NECs strongly favors these to be occult metastatic MCCs. True salivary primary NECs are likely exceedingly rare. When a high-grade NEC is encountered in the salivary gland, the presence of UV signature mutations or MCPyV may be useful to exclude occult unknown primary MCC.

A Report of 13 Cases of Merkel Cell Carcinoma: Single-Center Experience and Review of the Literature.

BackgroundThere is limited data knowledge of Merkel cell carcinoma (MCC) in Turkey aside from a few case reports.ObjectiveThe aim of this study was to describe the clinical characteristics, demographic features, therapeutic parameters, and outcome of primary cutaneous MCC cases from Turkey.MethodsDigital medical records of the 13 MCC patients who were followed-up at a tertiary referral center were retrospectively analyzed. Clinic, demographic, tumor characteristics, and survival of the patients were retrieved.ResultsMost of our patients were elderly. Female predominance was noticed. The most common primary site of the tumors was the lower extremities. The overall survival was 42 months, 68% at first year, 68% at third years, and 29% at fifth years.ConclusionThis is the first largest report from Turkish population with female predominance, and lower extremity tendency.

Analysis of cutaneous Merkel cell carcinoma outcomes after different surgical interventions

Current guidelines recommend local excision margin (EM) with 1 to 2cm on primary Merkel cell carcinoma (MCC) sites. We compared survival outcomes of patients with MCC who were treated with different surgical interventions. A retrospective analysis of MCC cases in the Surveillance, Epidemiology, and End Results database was performed using the Kaplan-Meier, competing risk, and Cox proportional hazards regression model analyses. Influence of age, T stage, American Joint Committee on Cancer stage, adjuvant radiotherapy, and other subgroups were also analyzed by pairwise log rank test. Our results indicated a significant association between local destruction method and inferior survival, while an EM >2cm showed significantly higher overall survival. In addition, the competing risk analysis depicted a similar trend as the Kaplan-Meier analysis, and considerably reduced estimated cumulative incidence. Further subgroup pairwise analysis demonstrated that the EM >2cm method had better survival in patients who were <60years of age, having smaller tumor diameters (T1 and T2) or having undergone adjuvant radiotherapy (P<.05). In contrast, different EMs did not show any significant association with survival rate in patients ≥75years of age or stage III tumors. This study was not prospectively randomized without relapse data. It is challenging to make optimal EM recommendations, because surgical options may depend on individual case situations. Further prospective randomized studies are warranted.