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

Generalized Acquired Cutis Laxa Associated with Monoclonal Gammopathy of Dermatological Significance

Background. Cutis laxa is a rare dermatosis that is inherited or acquired and clinically features loose, wrinkled, and redundant skin with decreased elasticity. This heterogeneous connective tissue disorder may be localized or generalized, with or without internal manifestations. Generalized cutis laxa often has a cephalocaudal progression and is attributed to inflammatory cutaneous eruptions, medications, and infections. Cutis laxa is also associated with several other conditions including rheumatoid arthritis, systemic lupus erythematosus, and plasma-cell dyscrasias. Case Presentation. We report an unusual case of a 35-year-old male with progression of generalized acquired cutis laxa and vasculitis that occurred over a period of one year. No cutaneous inflammatory eruption preceded or accompanied his decreased skin elasticity, and a biopsy of the skin showed elastolysis. His cutaneous manifestation led to systemic evaluation and an eventual diagnosis of smoldering multiple myeloma accompanied by aortitis and anemia. His myeloma and vasculitis were successfully treated with cyclophosphamide, bortezomib, and dexamethasone and high-dose prednisone, respectively, with no improvement to his cutis laxa. Conclusions. The presence of monoclonal gammopathy is strongly associated with several dermatological entities such as acquired cutis laxa. We propose a new term for the dermatological manifestations caused by paraproteinemia: monoclonal gammopathy of dermatological significance, or MGODS, and stress the evaluation of an underlying gammopathy in the setting of certain dermatologic conditions, including scleromyxedema and amyloidosis. We present a case of a newly acquired cutis laxa secondary to plasma-cell dyscrasias that exemplifies MGODS, alongside a brief literature review, and underscore the clinical relevance of monoclonal gammopathies of dermatological significance

Regionally Metastatic Merkel Cell Carcinoma Associated with Paraneoplastic Anti-N-methyl-D-aspartate Receptor Encephalitis

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer with a high risk of recurrence and metastasis. MCC is generally associated with advanced age, fair skin, sun exposure, immunosuppression, and in the majority of cases, the Merkel cell polyomavirus. Neuroendocrine malignancies are associated with a variety of paraneoplastic neurological syndromes (PNS), characterized as autoimmune responses to malignancy-associated expression of neural antigens. Our literature review underscores previous case reports of MCC-associated PNS with voltage-gated calcium channel (VGCC) and anti-Hu (or ANNA-1) autoantibodies. We present the case of a 59-year-old male with regionally metastatic Merkel cell carcinoma complicated by the paraneoplastic manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. His primary lower neck subcutaneous MCC and metastasis were initially treated with surgery. Additional recurrent lymph node metastases were successfully treated with definitive intensity-modulated radiation therapy. His PNS improved with rituximab therapy. Although rare, this case highlights that in the setting of seizures and prominent psychiatric symptoms accompanying an MCC diagnosis, evaluation for autoimmune paraneoplastic encephalitis is warranted. Awareness and detection of preexisting PNS are crucial in the era of immune checkpoint inhibitors (ICI) for advanced MCC, where treatment with ICI has the potential to exacerbate preexisting autoimmune PNS and lead to worsened or even lethal neurologic immune-related adverse events (nirAEs)

Metastatic Merkel Cell Carcinoma Masquerading as Multiple Immune-Related Adverse Events

Merkel cell carcinoma is a rare cutaneous neuroendocrine carcinoma with a high rate of regional and distant metastasis and mortality. Here, we report a novel case of Merkel cell carcinoma which presented as a primary lesion to the left cheek with regional lymph node involvement and was treated with pembrolizumab and radiation. Widely metastatic disease eventually revealed on autopsy clinically mimicked immune-related organ insult leading to management with immunosuppressants. The patient also had a biopsy-confirmed immune-related cutaneous adverse event during admission. The case highlights a rare circumstance in which disease progression masqueraded as multiple immune-related end-organ adverse events. Contribution of on-target anti-PD-1 toxicity remains a possibility

Impact of an evolving regulatory landscape on skin cancer drug development in the U.S.

Background: There has been a rapid proliferation of FDA-approved medications with labeled indications for skin cancer over the last decade, with particular growth over the last 5 years. Objective: We aimed to evaluate the impact of an evolving U.S. regulatory framework on drug development programs to better understand current trends and regulatory considerations when adjudicating drug approvals for patients with skin cancer. Methods: We reviewed publicly-available regulatory documents of all systemic medications with a labeled indication for skin cancer. Results: We identified 130 FDA approvals that resulted in a unique indication, usage, formulation, or dosage change in skin cancer since 1949. Limitations: Publicly available data from the mid-to-late 20th century is limited. Conclusions: The therapeutic landscape in skin cancer has changed greatly since the first approval in 1949. In concert, regulatory medicine has also evolved over the last 70 years with the aim of ensuring safe and effective medicines for a diverse array of patients