Primary Basal Cell Carcinoma Masquerading as Metastatic Basal Cell Carcinoma in the Left Axilla.

Basal cell carcinoma (BCC) is considered the most common malignancy in Caucasians. Despite its high prevalence, BCC has extremely low rates of metastasis. The patient was a 71-year-old male with extensive BCC and squamous cell carcinoma (SCC) skin cancer history who had an extensive, palpable left axillary mass concerning enlarged lymph nodes. No skin lesions were visualized. A lymph node biopsy revealed a sclerosing/infiltrative BCC with perineural invasion extending to the inked margins of the excision and one of four lymph nodes involved by BCC through direct extension. Sectioning revealed a 3.0 x 2.8 x 2.9 cm, ill-defined, fibrotic pink-white mass within the soft tissue. Two tan to pink possible lymph nodes were also identified within the soft tissue, measuring 0.7cm and 0.9cm. There was no definite direct invasion noted, making metastatic BCC suspicious. A left axillary lymph node dissection was performed. In short, he had a nonmobile tumor that showed evidence of invasion of the adjacent pectoralis muscle near the chest wall, abutting the left axillary vein, with extension. In July 2022, approximately one year after diagnosis, the patient received a PET scan and had no remote sites of disease. Every follow-up PET scan since has shown stable disease, most recently in May 2023. The patient continues dermatology follow-ups every three months for clinical surveillance. This case is unique because metastatic disease was never confirmed, though it is still a possibility. The affected lymph nodes were in the regional basin, where the patient had had extensive skin cancers in the past. Their involvement could have been secondary to direct invasion, though this could not be confirmed histologically, making the definitive characterization of this particular tumor difficult. As the PET CT scans have remained stable without evidence of distant disease, we favor that this is a recurrent primary tumor with direct extension to the underlying pectoralis and axillary lymph nodes. As common as BCCs are, this case highlights the importance of diligent treatment and follow-up to avoid the potential for tumor-related morbidity and, rarely, mortality.

The Matter of the Missing Melanoma: A Case Series.

Melanoma of the skin is the fifth most common malignancy in the U.S. In 2020, an estimated 6,850 people will die from melanoma of the skin. Further, given the broad distribution in ages affected, melanoma has a tremendous burden on health care costs and years of productive life lost. Every year, melanoma cases may go undetected, or have a significant delay in diagnosis, which may lead to poor outcomes. Here, three cases of melanoma encountered in the author's first clinical year of medical school, each of which had been overlooked, misdiagnosed, or lost to follow-up are reported. Implementing an integrated skin exam into every physical examination for high-risk patients and introducing preventative healthcare education into communities could help alleviate the burden of delay in diagnoses.

Aggressive Langerhans cell histiocytosis following T-cell acute lymphoblastic leukemia.

A 4-year-old female child developed cutaneous Langerhans cell histiocytosis 6 months following a diagnosis of T-cell acute lymphoblastic leukemia. Imaging revealed no evidence of systemic disease. Seven months later, the first systemic lesion was discovered on laryngoscopy. Restaging Positron Emission Tomography - Computed Tomography at that time revealed new 18-fluorodeoxyglucose-positive lesions in the left apical pleural margin, right lower peri-esophageal region, left ventricular myocardium, pancreas, upper pole of the left kidney, and inguinal and gluteal regions consistent with progressive systemic disease. Genomic testing revealed a low tumor mutational burden as well as mutations in KRAS G12A, ARID1A Q524, CDKN2A/B loss, and an alteration in NOTCH1.

Tumor Architecture and Notch Signaling Modulate Drug Response in Basal Cell Carcinoma.

Hedgehog (Hh) pathway inhibitors such as vismodegib are highly effective for treating basal cell carcinoma (BCC); however, residual tumor cells frequently persist and regenerate the primary tumor upon drug discontinuation. Here, we show that BCCs are organized into two molecularly and functionally distinct compartments. Whereas interior Hh+/Notch+ suprabasal cells undergo apoptosis in response to vismodegib, peripheral Hh+++/Notch- basal cells survive throughout treatment. Inhibiting Notch specifically promotes tumor persistence without causing drug resistance, while activating Notch is sufficient to regress already established lesions. Altogether, these findings suggest that the three-dimensional architecture of BCCs establishes a natural hierarchy of drug response in the tumor and that this hierarchy can be overcome, for better or worse, by modulating Notch.

Recurrence and Survival in Patients With Merkel Cell Carcinoma Undergoing Surgery Without Adjuvant Radiation Therapy to the Primary Site.

IMPORTANCE: The use of adjuvant radiation therapy (RT) to the primary site in Merkel cell carcinoma (MCC) is not uncommon. However, the need for adjuvant RT to the primary site in patients at low risk for local recurrence is questionable. OBJECTIVES: To examine the occurrence of true local, satellite, in-transit, regional, and distant recurrences in patients undergoing surgery alone without adjuvant RT to the primary site. To establish overall survival (OS), MCC-specific survival (MCCSS), and disease-free survival (DFS) relationships in a cohort of patients with MCC. DESIGN, SETTING, AND PARTICIPANTS: Our University of Michigan Multidisciplinary MCC Program database was used to obtain characteristics and outcome measures for 104 patients (105 primary MCCs) with tumors less than 2 cm in diameter. The majority of patients were treated between July 2006 and November 2012. MAIN OUTCOMES AND MEASURES: Outcome measures included the occurrence of true local, satellite, in-transit, regional, and distant recurrences. End points included OS, MCCSS, and DFS. RESULTS: Overall, information for 55 men and 49 women with 105 primary MCCs was obtained; 19 patients developed recurrent disease, and the mean time to first recurrence was 10.7 months. True local recurrence occurred in 1 patient with concurrent in-transit recurrence. Satellite recurrence occurred in 1 patient with concurrent regional recurrence. Four additional patients developed in-transit metastases. Thirteen patients had a regional recurrence component, 4 patients had distant metastases, and 6 patients developed subsequent regional and/or distant recurrences. Stratified by initial pathologic stage, the OS and MCCSS at 48 months were estimated to be 85.0% (95% CI, 71.8%-92.3%) and 94.4% (95% CI, 83.4%-98.2%) for patients with stage 1A/B disease and 63.2% (95% CI, 36.6%-81.1%) and 78.1% (95% CI, 50.0%-91.5%) for patients with stage 3A disease. The OS and MCCSS at 24 months for patients with stage 3B disease were both 50.0% (95% CI, 5.8%-84.5%). CONCLUSIONS AND RELEVANCE: In selected MCC patients with primary tumors less than 2 cm in diameter treated with surgery alone without adjuvant RT to the primary site, we found a low occurrence of true local recurrences and satellite recurrences. This relatively low rate of local recurrence questions the need for adjuvant RT to the primary tumor site in patients with small low-risk lesions.

Five-year outcomes of wide excision and Mohs micrographic surgery for primary lentigo maligna in an academic practice cohort.

BACKGROUND: Wide local excision with 5-mm margins is the standard of care for lentigo maligna (LM). Mohs micrographic surgery (MMS) is used increasingly to treat this tumor. OBJECTIVE: To study the authors' experience with these 2 approaches. MATERIALS AND METHODS: Primary LM cases treated at the authors' institution from January 1, 1995, through December 31, 2005, were studied retrospectively. Main outcome measures were recurrence and outcomes after treatment for recurrence. RESULTS: In total, 423 LM lesions were treated in 407 patients: 269 (64%) with wide excision and 154 (36%) with MMS. In the MMS group (primarily larger head and neck lesions with indistinct clinical margins), recurrence rates were 3 of 154 (1.9%). In the wide excision group (primarily smaller, nonhead and neck, or more distinct lesions), recurrence rates were 16 of 269 (5.9%). Each of the 16 recurrences was biopsy proven and treated surgically: 6 by standard excision and 10 by MMS. CONCLUSION: This follow-up study of LM surgical treatments shows excellent outcomes for wide excision and MMS. Because this is a nonrandomized retrospective study, no direct comparisons between the 2 treatments can be made. When recurrences occurred, repeat surgery, either standard excision or MMS, was usually sufficient to provide definitive cure.

NCCN Guidelines implementation in the multidisciplinary Merkel Cell Carcinoma Program at the University of Michigan.

Merkel cell carcinoma (MCC) is a rare malignancy of the skin, and prospective randomized clinical studies on management and treatment are very limited. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MCC provide up-to-date, best evidence-based, and consensus-driven management pathways with the purpose of providing best care and outcomes. Multidisciplinary management with consensus treatment recommendations to individualize patient care within the framework of these guidelines is optimal. The University of Michigan multidisciplinary MCC program uses NCCN Guidelines in the management and treatment of its patients. This article discusses 4 patient presentations to highlight the implementation of the NCCN Guidelines for MCC at the University of Michigan.

Incidence of lentigo maligna in Olmsted County, Minnesota, 1970 to 2007.

BACKGROUND: The incidence of lentigo maligna (LM) may be increasing, but no population-based epidemiologic studies have been performed to our knowledge. OBJECTIVE: We sought to determine the incidence of LM in Olmsted County, Minnesota, along with overall and recurrence-free survival. METHODS: Using the Rochester Epidemiology Project, we identified all adult residents of Olmsted County, Minnesota, with a first lifetime diagnosis of LM between 1970 and 2007. Medical records were reviewed to determine demographic, clinical, and surgical data, and incidence and survival were calculated. RESULTS: Among 145 patients identified, median (range) age at diagnosis of LM was 70 (33-97) years. Treatment changed over time, with Mohs micrographic surgery becoming available after 1986. No patients died of LM; 5 had local recurrence. Estimated local recurrence-free survival at 5, 10, 15, and 20 years after diagnosis was 98%, 96%, 92%, and 92%, respectively. Overall age- and sex-adjusted incidence of LM among adults was 6.3 per 100,000 person-years, increasing from 2.2 between 1970 and 1989 to 13.7 between 2004 and 2007. LIMITATIONS: Retrospective study design and homogeneous population are limitations. CONCLUSION: The incidence of LM increased significantly among residents of Olmsted County, Minnesota, over an extended time frame, with incidence being significantly higher among men than women and increasing with age.

Transcriptome profiling identifies HMGA2 as a biomarker of melanoma progression and prognosis.

The genetic alterations contributing to melanoma pathogenesis are incompletely defined, and few independent prognostic features have been identified beyond the clinicopathological characteristics of the primary tumor. We used transcriptome profiling of 46 primary melanomas, 12 melanoma metastases, and 16 normal skin (N) samples to find genes associated with melanoma development and progression. Results were confirmed using immunohistochemistry and real-time PCR and replicated in an independent set of 330 melanomas using AQUA analysis of tissue microarray (TMA). Transcriptome profiling revealed that transcription factor HMGA2, previously unrecognized in melanoma pathogenesis, is significantly upregulated in primary melanoma and metastases (P-values=1.2 × 10(-7) and 9 × 10(-5)) compared with N. HMGA2 overexpression is associated with BRAF/NRAS mutations (P=0.0002). Cox proportional hazard regression model and log-rank test showed that HMGA2 is independently associated with disease-free survival (hazard ratio (HR)=6.3, 95% confidence interval (CI)=1.8-22.3, P=0.004), overall survival (OS) (stratified log-rank P=0.008), and distant metastases-free survival (HR=6.4, 95% CI=1.4-29.7, P=0.018) after adjusting for American Joint Committee on Cancer (AJCC) stage and age at diagnosis. Survival analysis in an independent replication TMA of 330 melanomas confirmed the association of HMGA2 expression with OS (P=0.0211). Our study implicates HMGA2 in melanoma progression and demonstrates that HMGA2 overexpression can serve as an independent predictor of survival in melanoma.

Clinicopathologic features of primary Merkel cell carcinoma: a detailed descriptive analysis of a large contemporary cohort.

BACKGROUND: Little uniformity exists in the clinical and histologic variables reported with primary Merkel cell carcinoma (MCC). OBJECTIVE: To provide a rigorous descriptive analysis of a contemporary cohort and promote the prospective collection of detailed data on MCC for future outcome studies. METHODS AND MATERIALS: A detailed descriptive analysis was performed for clinical and histologic features of 147 patients with 150 primary MCC tumors in a prospectively collected database from 2006 to 2010. RESULTS: The majority (73.5%) of patients were at American Joint Committee on Cancer clinical stage I or II at presentation, 20.4% at stage III, and 6.1% at stage IV. Detailed descriptive clinical and histologic findings are presented. CONCLUSION: Clinical and histologic profiling of primary MCC in the literature is variable and limited. Systematic prospective collection of MCC data is needed for future outcome studies and the ability to compare and share data from multiple sources for this relatively rare tumor.

Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part I: Management of stage III disease.

The incidence of melanoma has increased for decades, and while surgical treatment of early stage disease is often curative, metastatic disease continues to carry a significantly less promising outlook with high associated health burden and economic cost. An expanding number of dermatologists are playing a key role in coordinating the care of patients with melanoma, including in an increasingly important role among multidisciplinary melanoma clinics, many of which are anchored in dermatology departments. Advances in the understanding of the genetic and immunoregulatory aspects of melanoma development and progression have yielded a wave of novel therapeutics that has made significant impact on the approach to patients with metastatic disease. Frequently updated management guidelines and unfamiliarity with approved adjuvant treatment options, including interferon, clinical trials, or radiation therapy, can pose a challenge for dermatologists seeking to effectively coordinate the care of and establish proper expectations for patients with stage III disease. Moreover, greater awareness of treatment modalities for in-transit disease may allow dermatologists to play a more active role in the treatment of these patients and to expand their ability to explain and coordinate options, such as limb perfusion or infusion. Part I of this continuing medical education article will use clinical scenarios to outline the current management options for patients with stage III melanoma, including both adjuvant treatment options for resected stage III disease and primary treatment options for in-transit metastases. Part II of this series will address stage IV disease.

Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part II: Management of stage IV disease.

Part II of this continuing medical education article will discuss the treatment options for stage IV melanoma, including novel therapies, such as ipilimumab and vemurafenib; established therapies, including high-dose interleukin-2, conventional chemotherapy, and biochemotherapy; and additional therapies currently under investigation in the form of clinical trials. The approach to patients with brain metastases will be discussed, as will recommendations for distress screening and defining aspects of palliative care.

Internet use and anxiety in people with melanoma and nonmelanoma skin cancer.

BACKGROUND: People with cancer are increasingly turning to the Internet for health-related information. OBJECTIVE: To compare the patterns of Internet use of people with skin cancer with previous findings by including people with nonmelanoma skin cancer (NMSC) using a comprehensive survey. To evaluate perceived anxiety levels and overall satisfaction after searching the Internet of people with skin cancer. METHODS & MATERIALS: We conducted a survey study and prospectively collected data from people newly diagnosed with melanoma or NMSC. RESULTS: Four hundred fifteen participants with melanoma and 400 with NMSC completed the questionnaire. Internet use and overall satisfaction with the Internet search increased more than 50% in participants with melanoma from 2005. One-third of participants with melanoma, but many fewer participants with NMSC, reported higher anxiety after Internet use. Participants who were younger, female, more highly educated, and diagnosed with melanoma were most likely to use the Internet to search for information about their diagnosis. CONCLUSION: Internet use is prevalent and increasing sharply in individuals with skin cancer. The majority of individuals describe their use of the Internet as a positive experience. Greater anxiety from searching the Internet is more common in individuals with melanoma than in those with NMSC.