Avelumab treatment for patients with metastatic Merkel cell carcinoma can be safely stopped after 1 year and a PET/CT-confirmed complete response.

BACKGROUND: Immune checkpoint inhibitor treatment of patients with metastatic Merkel cell carcinoma (mMCC) has shown high response rates, ranging from 33% to 73%. The ideal duration of treatment, however, is currently unknown. The aim of this study was to evaluate if avelumab treatment for mMCC can be safely stopped after 1 year of treatment and a complete response (CR) confirmed by fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging. METHODS: Patients who received more than one dose of avelumab treatment for mMCC between November 2017 and February 2022 were included in this study. Treatment was discontinued in case of a FDG-PET/CT confirmed CR after 1 year (26 cycles) of avelumab or a CR and unacceptable toxicity earlier. The primary end point was recurrence-free survival (RFS). RESULTS: Sixty-five patients were included: 25 (38%) had a FDG-PET/CT-confirmed CR at discontinuation of avelumab. In those 25 patients, reasons for discontinuation of treatment were completion of 1 year of treatment in 13 (52%), toxicity in five (20%), and patient preference in seven (28%). Median duration of treatment in this group was 11 months (interquartile range, 6.1-11.7). Median follow-up was 27 months (interquartile range, 15.8-33.8). The 12-month RFS was 88% (95% CI, 0.74-1) and median RFS was not reached. Two patients (8%) had a recurrence at 4 and 7 months after discontinuation of treatment. CONCLUSIONS: Patients with mMCC who acquire a CR on PET/CT imaging appear to have durable responses after discontinuation of treatment after 1 year.

18 F-FDG and 18 F-AIF-NOTA-Octreotide PET/CT Confirmed a Rare Case of Cutaneous Merkel Cell Carcinoma With a Solitary Local Nodal Metastasis.

ABSTRACT: Cutaneous Merkel cell carcinoma with local nodal metastasis is a rare entity. A 56-year-old man presented with a nontender left inguinal mass, and ultrasound-guided biopsy of this nodal mass confirmed nodal metastasis with strong neuroendocrine differentiation from cutaneous Merkel cell carcinoma. Staging 18 F-FDG PET/CT showed a solitary 3.9 × 6.8-cm hypermetabolic left groin mass with no other suspicious lesions elsewhere. To confirm the patient's eligibility for radical curative treatment, taking into consideration of its neuroendocrine differentiation, a subsequent 18 F-AIF-NOTA-octreotide PET/CT was performed, which demonstrated only solitary somatostatin receptor-positive left inguinal mass. The patient underwent radical treatment.

Reconstruction of Rapidly Growing Merkel Cell Carcinoma of the Cheek With Multidisciplinary Cooperation.

Merkel cell carcinoma (MCC) is a rare and very aggressive skin cancer. An 83-year-old female presented with a 1.5 cm-sized non-tender mass on her left cheek and was diagnosed with MCC. The margin of MCC was well-defined and there was no cervical node metastasis on pre-operative computed tomography. Three weeks after the first visit, the mass rapidly increased in size. We checked the magnetic resonance imaging, a rapid-growing 2.5 cm sized nodular region and metastatic cervical lymph node were found. We performed wide excision of the MCC and neck lymph need dissection with multidisciplinary cooperation. The soft tissue defect was about 6.0×5.0 cm 2 in size and reconstructed with radial forearm free flap. On permanent biopsy, the size of MCC was 3.0×2.3 cm 2 . There was no recurrence of MCC with radiation therapy during an 18-month follow-up. We experienced an older patient with a rapid - growing MCC and cervical lymph node metastasis in a brief time. With our experience, we discuss the evaluation and treatment plan of the rapid-growing MCC for good results.

Baseline ultrasound and FDG-PET/CT imaging in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous tumor with a high tendency to metastasize, and a significant proportion of patients have metastases at first presentation. This study aims to determine the value of baseline ultrasound (US) and 18 fluorodeoxyglucose-positron emission tomography/computed tomography (18 FDG-PET/CT) imaging in both patients with clinically localized MCC (Stage I/II) and patients who present with palpable lymph nodes (Stage III). METHODS: This retrospective cohort included 135 MCC patients who underwent baseline US (with fine needle aspiration cytology (FNAC)) and/or FDG-PET/CT imaging between 2015 and 2021. RESULTS: Of the 104 patients with clinically localized disease, 48% were upstaged to Stage III and 3% to Stage IV by imaging or sentinel lymph node biopsy (SLNB). FDG-PET/CT imaging identified regional metastases in 23%, while US with FNAC identified regional metastases in 19%. SLNB was performed in 56 patients, of whom 57% were upstaged to Stage III. Of the 31 patients who presented with palpable lymph nodes, 16% were upstaged to Stage IV by FDG-PET/CT imaging. CONCLUSION: Baseline imaging frequently upstages Stage I/II MCC patients to Stage III, both by US and FDG-PET/CT, Stage IV disease is rarely identified. Patients who present with palpable nodes are frequently upstaged to Stage IV by FDG-PET/CT imaging.

Diagnostic Test Accuracy of 18 F-FDG PET or PET/CT in Merkel Cell Carcinoma.

OBJECTIVE: The purpose of the current study was to evaluate the diagnostic accuracies of 18 F-FDG PET or PET/CT for diagnosis of Merkel cell carcinoma (MCC) through a systematic review and meta-analysis. METHODS: The PubMed, Cochrane database, and EMBASE database, from January 1990 to January 31, 2022, were searched for studies evaluating diagnostic performance of 18 F-FDG PET or PET/CT for MCC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. RESULTS: Across 9 studies (259 patients), the pooled sensitivity of 18 F-FDG PET or PET/CT was 0.91 (95% confidence interval [CI], 0.85-0.95) and a pooled specificity of 0.93 (95% CI, 0.86-0.97). Likelihood ratio syntheses gave an overall LR+ of 14.0 (95% CI, 6.6-29.6) and LR- of 0.09 (95% CI, 0.05-0.17). The pooled diagnostic odds ratio was 153 (95% CI, 57-416). CONCLUSION: 18 F-FDG PET/CT showed an excellent performance for diagnosis of MCC. The likelihood ratio scattergram indicated that 18 F-FDG PET or PET/CT is useful for exclusion and confirmation of MCC. Further large multicenter studies would be necessary to substantiate the diagnostic accuracy of 18 F-FDG PET or PET/CT for MCC patients.

18F-FDG PET/CT for Posttreatment Surveillance Imaging of Patients with Stage III Merkel Cell Carcinoma.

The purpose of this study was to investigate the diagnostic and prognostic value of 18F-FDG PET/CT for surveillance imaging in patients treated for stage III Merkel cell carcinoma (MCC). Methods: This retrospective study included 61 consecutive stage III MCC patients who were clinically asymptomatic and underwent surveillance 18F-FDG PET/CT. Findings were correlated with either pathology or clinical/imaging follow-up. The median follow-up period was 4.8 y. Statistical analyses were performed. Results:18F-FDG PET/CT detected unsuspected recurrences in 33% patients (20/61) with lesion-based sensitivity, specificity, and accuracy of 92%, 93%, and 93%, respectively. The mean ± SD SUV for malignant and benign lesions was 7.5 ± 3.9 and 3.8 ± 2.0, respectively. Unknown distant metastases, as first recurrence site, were noted in 12 of 61 patients. Those with positive disease on 18F-FDG PET/CT within 1 y of definitive treatment had relatively worse overall survival (P < 0.0001). After adjustment on stage, risk of death increased with a higher SUVmax (hazard ratio for 1 unit = 1.17; P = 0.006) and with a higher number of positive lesions on 18F-FDG PET/CT (hazard ratio for 1 additional lesion = 1.60; P < 0.001). Conclusion: Postdefinitive treatment surveillance 18F-FDG PET/CT scanning detects unsuspected recurrences and has prognostic value. Inclusion of 18F-FDG PET/CT within the first 6 mo after definitive treatment would be appropriate for surveillance and early detection of recurrence. Our data merit further studies to evaluate the prognostic implications.

Abdominal metastases from Merkel cell carcinoma: Prevalence and presentation on CT examination in 111 patients.

PURPOSE: The purpose of this study was to report the prevalence and imaging features of abdominal metastases from Merkel cell carcinoma (MCC) on computed tomography (CT) examinations. MATERIALS AND METHODS: A total of 111 patients with MCC from two institutions were initially identified. Of these, 27 patients (27/111; 24.3%) had abdominal metastases from MCC present on CT examination. There were 19 men and 8 women with a mean age of 75  ± 10.8 (SD) years (age range: 46-92 years). CT examinations were retrospectively reviewed by two radiologists and analyzed quantitatively for the number and dimensions of abdominal metastases from MCC and qualitatively in terms of location, margins, contours, homogeneity, patterns of enhancement, vascular involvement and extension of metastases from MCC. RESULTS: Fifteen patients (15/27; 56%) had abdominal metastatic disease at initial diagnosis and twelve (12/27; 44%) developed abdominal metastases during the course of the disease. The mean number of locations of abdominal metastases was 2.1 ± 1.12 (SD) (range: 1-5). Abdominal metastases involved abdominal lymph nodes (16/27; 59%), adrenal glands/kidneys/retroperitoneum (14/27; 52%), mesentery/peritoneum (13/27; 48%), liver (7/27; 26%) and pancreas (7/27; 26%). Vascular involvement was found in association with peritoneal/mesenteric metastases in 6/13 (46%) patients with intraperitoneal metastases or in association with abdominal lymph nodes in 4/16 (25%) patients. Ureteral encasement and/or dilatation was found in 4/14 (28%) patients with retroperitoneal metastases and 3/16 (19%) patients with abdominal lymph nodes. Metastases to the liver, pancreas, peritoneum, retroperitoneum and adrenal glands displayed internal enhancement during the arterial phase in 1/2 (50%), 4/5 (80%), 4/7 (57%) and 5/8 (62%) patients for whom arterial phase was available, respectively. CONCLUSION: Metastases from MCC have a prevalence of 24.3% on CT examination and may involve a variety of abdominal organs, mainly lymph nodes, peritoneal and retroperitoneal structures, but also the liver and pancreas. CT features of abdominal metastases from MCC include hypervascularity during the arterial phase of enhancement and eventually vascular and ureteral involvement.

Merkel cell carcinoma of the breast: A case report.

Merkel cell carcinoma (MCC) of the breast is a very rare and aggressive type of neuroendocrine carcinoma of the breast (NECB) that typically occurs in older and immunocompromised individuals often presenting as a large palpable mass (Albright et al., 20181). Imaging features of MCC are similar to other NECBs, typically appearing as an oval circumscribed mass on mammography and as an irregular mass with increased vascularity on sonography (Jeon et al., 20142). While both MCC and primary NECB demonstrate positive immunostaining for synaptophysin, obtaining immunohistochemical stains for specific markers, such as CK7 and CK20 is imperative to confirm the diagnosis of MCC (Albright et al., 20181). We present a case of a 57-year-old female patient with no personal or family history of breast cancer, who presented for evaluation of a palpable abnormality in her left breast. Initial diagnostic mammogram demonstrated a circumscribed mass in the upper outer quadrant of the left breast corresponding to the palpable area of concern, which correlated to an irregular mass with increased vascularity on targeted ultrasound, similar to other NECBs. Pathologic results after tissue sampling yielded poorly differentiated primary NECB. Following neoadjuvant chemotherapy, the patient underwent a lumpectomy and further immunohistochemical stains of the lumpectomy specimen demonstrated diffusely positive synaptophysin, negative CK7, and positive CK20, consistent with MCC of the breast.

Immunotherapy in advanced Merkel cell carcinoma: Sydney west cancer network experience.

INTRODUCTION: Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with no survival benefit demonstrated using palliative cytotoxic chemotherapy in the setting of metastatic MCC. Recently, immune checkpoint inhibitors (anti-PD-L1/PD1) have been approved in this setting after durable clinical response was demonstrated in several clinical trials. In this series, we present a multicentre real-world experience in using anti-PD-L1/PD1 in advanced MCC. METHODS: A retrospective review was performed of all patients with metastatic MCC who were treated with at least one dose of anti-PD-L1/PD1 presenting to Sydney West Cancer Network (Westmead, Nepean and Blacktown hospitals) was performed between 2016 and 2020. Treatment response was assessed based on morphologic and/or metabolic changes of the disease on FDG-PET/CT scans. Primary end point investigated was objective response rate. Secondary outcomes included therapy toxicity, disease control and overall survival. RESULTS: Thirteen patients received anti-PD-L1/PD1 with a median age of 82 (range 62-89). Two patients had undergone prior palliative chemotherapy. The median follow-up time was 17 months (range 2-34). The overall, complete and partial response rates were 77% (10), 54% (7) and 23% (3), respectively. Treatment-related grade 1 or 2 toxicity was experienced by 69% with only 2 cases of greater severity. The median progression-free survival and overall survival were 18 months (95% CI 10-26 months) and 33 months (95% CI range 7.6-58.4 months), respectively. CONCLUSIONS: Consistent with clinical trial results, anti-PD-L1/PD1 therapy in this small series demonstrated efficacy and safety in patients with metastatic MCC.

How we treat Merkel cell carcinoma: within and beyond current guidelines.

Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with a high risk of local recurrence and distant metastasis. Optimal care of this potentially life-threatening cancer is critical but challenging because: physicians are often unfamiliar with its management due to rarity, and MCC management remains controversial, in part because it is rapidly evolving across multiple specialties. While guidelines offer a broad overview of management, they are often not sufficient when making decisions for individual patients. Herein, we present a literature review as well as practical approaches adopted at our institutions for staging, surveillance and therapy of MCC. Each of these areas are discussed in light of how they can be appropriately customized for prevalent but challenging situations. We also provide representative examples of MCC patient scenarios and how they were managed by a multidisciplinary team to identify suitable evidence-based, individualized treatment plans.

Lay abstract Merkel cell carcinoma (MCC) is a skin cancer with a high risk of recurrence and distant spread. Optimal care of this cancer is important. However, management is challenging because it is rare and its treatment is continuously evolving across multiple specialties. While treatment guidelines offer a broad overview of management, they are often not detailed enough to provide appropriate patient-specific assistance. Herein, we present a review of recent studies and our suggestions relevant to MCC staging, surveillance and treatment options. Each of these areas are discussed in light of how they can be appropriately customized for challenging situations often encountered by practitioners. We also provide representative examples of MCC patient scenarios and how they were managed by a multidisciplinary team to identify evidence-based, individualized treatment plans.

Clinical Impact of FDG PET/CT of the Lower Extremities in Patients With Merkel Cell Carcinoma With Primary Disease Site Outside of the Lower Extremities.

OBJECTIVE. Whole-body imaging extending from the vertex of the head to the toes is considered the standard 18F-FDG PET/CT protocol for Merkel cell carcinoma, though the evidence establishing this standard is scant. The purpose of this study was to investigate the clinical impact of PET/CT of the lower extremities in patients with Merkel cell carcinoma, a rare aggressive neuroendocrine tumor of the skin. MATERIALS AND METHODS. A total of 101 patients with Merkel cell carcinoma (mean age, 70.9 years) who underwent whole-body PET/CT were included. PET/CT findings in the lower extremities were evaluated on a per-patient basis, and the results were compared between patients with the primary lesion in the lower extremities (lower extremity primary) and those with the primary lesion located between the head and inguinal regions (body primary). Subsequent clinical evaluation and follow-up imaging were used as the reference standard. RESULTS. In the lower extremity (n = 22) and body (n = 79) primary groups, five and eight patients had true metastases in the lower extremities (p = .15). In the body primary group, all metastases in the lower extremities were part of widespread metastases in the body. In contrast, three of five patients (60%) in the lower extremity primary group had isolated metastases in the lower extremities, which differed significantly from the rate in the body primary group (p = .04). Subgroup analysis that included 48 patients who underwent initial staging examinations showed no metastases in the lower extremities regardless of primary location. CONCLUSION. PET/CT of the lower extremities for patients with body primary lesions of Merkel cell carcinoma should be considered of limited clinical utility.

Characteristic Imaging Features of Merkel Cell Carcinoma: A Case Report.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary cutaneous tumor. The standardized imaging guidelines for the diagnosis of MCC have not been established. We report the multimodality imaging features of MCC, including CT, MRI, and ultrasound with grayscale and color Doppler mode as well as the elastography and even a histopathologic confirmation. CASE REPORT: We report the case of a 76-year old male patient with MCC on the elbow that was treated by excision. On MRI, prominent T2 low signal voiding was noted with branching or chaotic pattern and marked, branching, or chaotic vascularity was also seen on color doppler ultrasound. Those findings corresponded to histology that showed increased vascularity in stromal tissues of the tumor and in between the tumor cells. CONCLUSION: A mass in the dermal and subcutaneous layer with marked and branching or chaotic vascularity may be the unique characteristic that may contribute to early diagnosis of MCC.

Patterns of Metastasis in Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied. METHODS: Patients with American Joint Committee on Cancer (8th edition) stage I-IV MCC treated at our institution were identified (1/1/2008-2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated. RESULTS: Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20-66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002). CONCLUSIONS: Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.

Pancreatic metastasis of Merkel-cell carcinoma: a rare neoplasm of the pancreas.

Only 2-3.9% of pancreatic malignancies represent metastases from other sites, the most common origins being the lungs, kidneys, and gastrointestinal tract. Differentiating between primary and secondary lesions may be challenging with imaging techniques but EUS-guided FNA is a safe, accurate procedure for obtaining a tissue diagnosis. We report the case of a 70-year-old male who, following satisfactory treatment for a Merkel-cell carcinoma in the right groin, presented with jaundice and an indurated, vascularized, adherent nodule on the right thigh. Endoscopic ultrasound identified a mass at the pancreatic head as well as a perilesional adenopathy with no evidence of vascular involvement. FNA revealed cell proliferation, which was immunohistochemically positive for CD56, synaptophysin, and chromogranin, these findings being consistent with poorly-differentiated neuroendocrine carcinoma. Given the patient's history we considered this lesion to be a pancreatic metastasis of Merkel-cell carcinoma, which represents a rare finding.