Combinations of EGFR and MET inhibitors reduce proliferation and invasiveness of mucosal melanoma cells.

Mucosal melanoma (MM) is a very rare and aggressive type of cancer for which immunotherapy or targeted therapy such as BRAF/MEK inhibitors, used in cutaneous melanoma, usually fail. Due to our earlier experience showing the high effectiveness of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) inhibitors in reducing the activation of the MAPK and PI3K/AKT signalling pathways, we aim to test whether these drugs would also be effective for mucosal melanoma. Cells representing two commercially available mucosal melanoma cell lines (GAK and HMVII) and one cell line obtained from a patient's vaginal melanoma were treated with MET or EGFR inhibitors, or combinations of these agents. The dual-inhibitor treatment strategy resulted in a decrease of cell proliferation, migration and invasion. Moreover, combinations of inhibitors led to reduction of pEGFR/EGFR and pMET/MET ratio and downregulation of PI3K/AKT and MEK/ERK1/2-based signalling pathways. Our findings indicate a potential therapeutic strategy based on EGFR and MET inhibitors in mucosal melanoma, which should be further evaluated in vivo and in clinical experiments. They also suggest that targeting multiple receptor tyrosine kinases may block signalling crosstalk and possibly delay the appearance of resistance to kinase inhibitors in mucosal melanoma cells.

Expression of Genes Associated With Epithelial-Mesenchymal Transition in Merkel Cell Polyomavirus-Negative Merkel Cell Carcinoma.

Two accepted possible pathways for Merkel cell carcinoma (MCC) pathogenesis include the clonal integration of the Merkel cell polyomavirus (MCPyV) into the neoplastic cells and by UV irradiation. We hypothesize that, in UV etiology, the expression of genes associated with epithelial-mesenchymal transition (EMT) would be higher in MCPyV-negative MCCs. We compared RNA expression in 16 MCPyV-negative with that in 14 MCPyV-positive MCCs in 30 patients using NanoString panel of 760 gene targets as an exploratory method. Subsequently, we confirmed the findings with a publicly available RNA sequencing data set. The NanoString method showed that 29 of 760 genes exhibited significant deregulation. Ten genes (CD44, COL6A3, COL11A1, CXCL8, INHBA, MMP1, NID2, SPP1, THBS1, and THY1) were part of the EMT pathway. The expression of CDH1/E-cadherin, a key EMT gene, and TWIST1, regulator gene of EMT, was higher in MCPyV-negative tumors. To further investigate the expression of EMT genes in MCPyV-negative MCCs, we analyzed publicly available RNA sequencing data of 111 primary MCCs. Differential expression and gene set enrichment analysis of 35 MCPyV-negative versus 76 MCPyV-positive MCCs demonstrated significantly higher expression of EMT-related genes and associated pathways such as Notch signaling, TGF-ß signaling, and Hedgehog signaling, and UV response pathway in MCPyV-negative MCCs. The significance of the EMT pathway in MCPyV-negative MCCs was confirmed independently by a coexpression module analysis. One of the modules (M3) was specifically activated in MCPyV-negative MCCs and showed significant enrichment for genes involved in EMT. A network analysis of module M3 revealed that CDH1/E-cadherin was among the most connected genes (hubs). E-cadherin and LEF1 immunostains demonstrated significantly more frequent expression in MCPvV-negative versus MCPyV-positive tumors (P < .0001). In summary, our study showed that the expression of EMT-associated genes is higher in MCPyV-negative MCC. Because EMT-related proteins can be targeted, the identification of EMT pathways in MCPyV-negative MCCs is of potential therapeutic relevance.

Histologic margin status is a predictor of relapse in lentigo maligna melanoma.

BACKGROUND: Most surgical margins for lentigo maligna melanomas reported in the literature are clinical and not histologic. OBJECTIVES: We sought to determine whether histologic margin status is an independent predictor of progression. METHODS: Clinicopathologic information of 268 invasive lentigo maligna melanomas diagnosed from 1990-2019 were analyzed. Statistical analyses were performed using Cox proportional hazards model and Boruta method. RESULTS: A total of 75% of the lesions were located on the head and neck. The range of follow-up for all patients was 0 to 31.8 years (median, 10.2 years). Time to local recurrence ranges from 0 to 20 years (median, 3 years). Progression developed in 54 (20.1%) of 268 patients. Local recurrence was seen only in 36 (13.4%), both local recurrence and subsequent metastasis in 7 (2.6%), and only metastasis in 11 (4.1%) of 268 patients. Histologic margin status (positive and close/<3 mm) and tumor site (head and neck location) significantly correlated with worse progression-free survival. LIMITATIONS: Single institution and retrospective study. CONCLUSIONS: Histologic margin status is the strongest predictor of progression for lentigo maligna melanoma. Patients with positive or close/<3 mm histologic margins should consider a re-excision due to the increased risk of relapse.

Implementation and Clinical Adoption of Precision Oncology Workflows Across a Healthcare Network.

BACKGROUND: Precision oncology relies on molecular diagnostics, and the value-proposition of modern healthcare networks promises a higher standard of care across partner sites. We present the results of a clinical pilot to standardize precision oncology workflows. METHODS: Workflows are defined as the development, roll-out, and updating of disease-specific molecular order sets. We tracked the timeline, composition, and effort of consensus meetings to define the combination of molecular tests. To assess clinical impact, we examined order set adoption over a two-year period (before and after roll-out) across all gastrointestinal and hepatopancreatobiliary (GI) malignancies, and by provider location within the network. RESULTS: Development of 12 disease center-specific order sets took ~9 months, and the average number of tests per indication changed from 2.9 to 2.8 (P = .74). After roll-out, we identified significant increases in requests for GI patients (17%; P < .001), compliance with testing recommendations (9%; P < .001), and the fraction of "abnormal" results (6%; P < .001). Of 1088 GI patients, only 3 received targeted agents based on findings derived from non-recommended orders (1 before and 2 after roll-out); indicating that our practice did not negatively affect patient treatments. Preliminary analysis showed 99% compliance by providers in network sites, confirming the adoption of the order sets across the network. CONCLUSION: Our study details the effort of establishing precision oncology workflows, the adoption pattern, and the absence of harm from the reduction of non-recommended orders. Establishing a modifiable communication tool for molecular testing is an essential component to optimize patient care via precision oncology.

Identification of fusions with potential clinical significance in melanoma.

Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions, mutations, and copy number changes, were performed on 750 melanomas (375 primary and 375 metastases) at our institution from 2014-2021. These included 599 (80%) cutaneous, 38 (5%) acral, 11 (1.5%) anorectal, 23 (3%) sinonasal, 27 (3.6%) eye (uveal/ conjunctiva), 11 (1.5%) genital (vulva/penile), and 41 (5.5%) melanomas of unknown primary. Sixteen fusions (2%) were detected in samples from 16 patients: 12/599 (2%) cutaneous, 2/38 (5%) acral, 1/9 (11%) vulva, 1/23(4.3%) sinonasal; and 12/16 (75%) fusions were potentially targetable. We identified two novel rearrangements: NAGS::MAST2 and NOTCH1::GNB1; and two fusions that have been reported in other malignancies but not in melanoma: CANT1::ETV4 (prostate cancer) and CCDC6::RET (thyroid cancer). Additional fusions, previously reported in melanoma, included: EML4::ALK, MLPH::ALK, AGAP3::BRAF, AGK::BRAF, CDH3::BRAF, CCT8::BRAF, DIP2B::BRAF, EFNB1::RAF1, LRCH3::RAF1, MAP4::RAF1, RUFY1::RAF1, and ADCY2::TERT. Fusion positive melanomas harbored recurrent alterations in TERT and CDKN2A, among others. Gene fusions were exceedingly rare (0.2%) in BRAF/RAS/NF1-mutant tumors and were detected in 5.6% of triple wild-type melanomas. Interestingly, gene rearrangements were significantly enriched within the subset of triple wild-type melanomas that harbor TERT promoter mutations (18% versus 2%, p < 0.0001). Thirteen (81%) patients were treated with immunotherapy for metastatic disease or in the adjuvant setting. Six of 12 (50%) patients with potentially actionable fusions progressed on immunotherapy, and 3/6 (50%) were treated with targeted agents (ALK and MEK inhibitors), 2 off-label and 1 as part of a clinical trial. One patient with an AGAP3::BRAF fusion positive melanoma experienced a 30-month long response to trametinib. We show that, detecting fusions, especially in triple wild-type melanomas with TERT promoter mutations, may have a clinically significant impact in patients with advanced disease who have failed front-line immunotherapy.

Cutaneous Findings of Sporadic, Adult-Onset Neuronal Intranuclear Inclusion Disease.

ABSTRACT: Neuronal intranuclear inclusion disease is a rare, progressive neurodegenerative disease whose hallmark histopathologic finding is the presence of ubiquitin-positive hyaline intranuclear inclusions in neuronal and non-neuronal cells. We present a case of neuronal intranuclear inclusion disease in a 61-year-old Asian man with a history of repeated episodes of altered mental status, long-standing bladder dysfunction, and cerebrovascular accidents. The patient had characteristic magnetic imaging findings of high signal along the cortico-medullary junction on diffusion-weighted sequences and symmetric T2 hyperintensity in the paravermal area of the cerebellum. Skin biopsies showed characteristic histopathologic findings of ubiquitin-positive intranuclear inclusions that ultrastructurally composed of filamentous material without limiting membrane within eccrine epithelium and dermal fibroblasts. Our case highlights the utility of readily accessible skin biopsy in the diagnosis of this rare neurodegenerative disease.

Skin biopsy in the diagnosis of intravascular lymphoma: A retrospective diagnostic accuracy study.

BACKGROUND: The yield of skin biopsies in the evaluation of intravascular lymphoma (IVL) is largely unknown in Western patients. Most data supporting this test come from Asian populations, in which both prevalence and disease presentation seem to differ. OBJECTIVE: To determine the yield and diagnostic properties of skin biopsy in the evaluation of IVL. METHODS: We reviewed skin biopsy pathology reports of 50 patients being evaluated for IVL to calculate the diagnostic yield of this test. An additional 6 patients, who underwent skin biopsies after the diagnosis of IVL was made by other means, were included to calculate the sensitivity and specificity of our index test. RESULTS: Skin biopsy samples were positive for 5 of the 50 patients being investigated for IVL. Sensitivity was 50% and specificity was 100%. LIMITATIONS: Only pathology reports containing IVL as an indication for the biopsy were retrieved. This might have excluded patients in whom the disease was considered but was not deemed likely enough to be listed as the indication for the test, inflating our estimative of skin biopsy yield. CONCLUSION: A relatively high diagnostic yield was found in the evaluation of IVL among patients with a diverse presentation in a Western hospital.

Metastasizing basal cell carcinoma: A clinicopathologic and immunohistochemical study of 22 cases.

Basal cell carcinomas metastasize rarely, and there have been limited studies of potential drivers for this metastasis. Epithelial-mesenchymal transition (EMT) may play a role, although this has not been investigated in detail. We reviewed clinicopathologic features of 22 patients with metastasizing basal cell carcinoma (MBCC). Immunohistochemical markers of EMT, including CD44, E-cadherin, claudin, smooth muscle actin, beta-catenin, Twist1, and Oct 3/4, were evaluated on 10 MBCC (primary and metastases) and 18 non-metastasizing BCC. Primary sites included the head and neck, trunk, and extremity, while metastatic sites included lymph nodes, lung, bone, and soft tissue. Of 19 cases with follow-up, the range of follow-up after diagnosis of metastasis was 5 to 248 months (median: 50 months). Two cases were of unknown primary, nine metastases were diagnosed concurrently with primary tumors, and remaining cases showed a median latency between diagnosis of primary and metastatic tumors of 27.5 months (range: 3-81 months). Median survival was 66 months. Compared to non-metastasizing BCC, MBCC demonstrated reduced CD44 expression (primary [P = .0036], metastatic [P = .011]) and increased Twist1 expression (primary, P = .0017). MBCC shows variably aggressive behavior, and reduced CD44 and increased Twist1 expression may indicate significant EMT in metastasizing tumors and signify a metastatic phenotype.

Distinction Between Hypertrophic Lichen Planus and Squamous Cell Carcinoma Requires Clinicopathologic Correlation in Difficult Cases.

ABSTRACT: Distinguishing hypertrophic lichen planus (HLP) and squamous cell carcinoma (SCC) can be diagnostically challenging because of overlapping clinical and histopathological features. This study characterizes histopathological features in HLP and SCC, assessing their utility in diagnosing atypical squamous proliferations. We compared 12 histopathological features of 15 HLP and 11 SCC biopsies from the lower extremities. We then reviewed 16 cases that were diagnosed as atypical squamous proliferations with differential diagnoses of HLP versus SCC. Clinical follow-up allowed for retrospective categorization of these difficult cases as HLP or SCC. HLP showed significant differences in hyperorthokeratosis (P = 0.04), wedge-shaped hypergranulosis (P = 0.0033), and irregular psoriasiform hyperplasia (P = 0.004), whereas parakeratosis (P = 0.001), solar elastosis (P = 0.001), deep extension (P = 0.02), and perforating elastic fibers (P = 0.0001) were significant for SCC. A scoring system based on these significant differences was devised to aid the classification of difficult cases. 56% of the difficult cases received an "indeterminate" score. A score favoring HLP had a sensitivity of 44% and a specificity of 71%. Although significant differences were identified between cases of definitive HLP and SCC, these histopathological features were unable to distinguish difficult cases, highlighting the need for clinicopathological correlation in patients with atypical squamous proliferations of the lower extremities. Many difficult cases had histologic features that could not be evaluated because of the superficial nature of the biopsy. Therefore, obtaining a deep wedge or punch biopsy may facilitate a diagnosis in cases with a differential diagnosis of HLP and SCC.

Molecular Alterations in Vaginal Melanomas: Report of 4 Cases and Literature Review.

ABSTRACT: Melanomas of the female gynecological tract comprise approximately 18% of mucosal melanomas, a rare subtype of melanoma. Within the female genital tract, 70% of primary melanomas of the gynecological tract are from the vulva with the remainder occurring in the vagina and rarely, in the cervix. We investigate molecular alterations by next-generation sequencing-based molecular tests targeting 99 cancer genes and translocation/fusion assays in 4 and 3 vaginal melanomas, respectively. The ages of the 4 patients range from 65 to 90 years. Postmenopausal bleeding was the most common presenting symptom. Tumor size ranged from 0.5 to 6.6 cm. KIT L576P mutation was documented in case 1, whereas TP53 mutation was seen in cases 2 and 3 (L130F and Y163C). Case 2 also harbored NF2 E204Q and ATRX D1719H mutations. A number of gene copy alterations were noted in case 4, which included GNA11 loss, MYC gain, RET loss, SMO loss, SUFU loss, and TSC2 loss. No gene fusion was detected in any of the 3 tested cases. In conclusion, in addition to KIT, TP53, and ATRX mutations, which have been previously reported, our cases harbor NF2 mutation and multiple gene copy alterations that have not previously been documented in vaginal melanomas. These findings highlight the potential role of targeted therapy in this rare melanoma subtype.

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.

Prognostic implications of normal or minimal urinary findings on long-term renal impairment in adults with Henoch-Schönlein purpura.

BACKGROUND: Renal involvement in adult Henoch-Schönlein purpura is a major cause of morbidity and can lead to significant long-term renal impairment. The prognostic significance of normal or minimal urinary abnormalities at diagnosis is unknown. OBJECTIVE: To assess the risk of long-term renal impairment in patients with Henoch-Schönlein purpura who present with normal or minimal urinary abnormalities. METHODS: Retrospective cohort study of adult Henoch-Schönlein purpura patients presenting with normal urinalysis results, microscopic hematuria, or low-grade proteinuria. Patients were followed for development of long-term renal impairment, with adjusting for comorbidities. RESULTS: Forty-seven patients were included, with median follow-up 73.9 months (interquartile range 35 to 98 months). Thirty-nine patients (83.0%) had abnormal urinalysis results, of whom 15 (38.5%) progressed to long-term renal impairment. In contrast, 8 patients (17%) had normal urinalysis results, of whom only 1 (12.5%) developed long-term renal impairment (adjusted hazard ratio 10.58; 95% confidence interval 1.18-94.73). Renal events occurred at a median 36.1 months (interquartile range 17.1 to 61 months) from diagnosis, earlier in patients with comorbidities compared with those with none, and in a constant event rate over time. LIMITATIONS: Small sample size. CONCLUSIONS: Microscopic hematuria and low-grade proteinuria at Henoch-Schönlein purpura diagnosis is a poor prognostic sign for the development of long-term renal impairment. This population should be targeted for prolonged surveillance.

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.

Case Records of the Mass General Hospital. Case 7-2015: A 25-year-old man with oral ulcers, rash, and odynophagia.

A 25-year-old man presented with oral ulcers and odynophagia. On examination, there were scattered pink papules and plaques on the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins. A diagnostic procedure was performed.

Location of skin lesions in Henoch-Schönlein purpura and its association with significant renal involvement.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a small vessel IgA-predominant vasculitis. OBJECTIVE: To describe adult patients with HSP and determine if the distribution of skin lesions (ie, purpura above the waist or purpura below the waist only), is a predictor of significant renal involvement at the time of the skin biopsy and the months following. METHODS: A retrospective study on renal function from 72 adult patients with skin-biopsy proven HSP. Longitudinal renal data were analyzed after HSP diagnosis by using baseline renal function for comparison. RESULTS: Statistical analysis adjusted for sex, age, and baseline creatinine revealed a trend between HSP lesions only on the upper and lower extremities and long-term renal involvement (4.767, P = .067). Moreover, in another analysis adjusted for age and baseline creatinine, lesions located only on the upper and lower extremities significantly increased the odds of having long-term significant renal involvement (6.55, P = .049) in men. LIMITATIONS: This retrospective study used patient information that was subject to selection bias. CONCLUSION: In patients with HSP, skin lesion distribution on the extremities might be predictive of significant long-term renal involvement and might be critical for risk stratification and development of personalized diagnostics and therapeutics.

An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background.

People with pale skin, red hair, freckles and an inability to tan--the 'red hair/fair skin' phenotype--are at highest risk of developing melanoma, compared to all other pigmentation types. Genetically, this phenotype is frequently the product of inactivating polymorphisms in the melanocortin 1 receptor (MC1R) gene. MC1R encodes a cyclic AMP-stimulating G-protein-coupled receptor that controls pigment production. Minimal receptor activity, as in red hair/fair skin polymorphisms, produces the red/yellow pheomelanin pigment, whereas increasing MC1R activity stimulates the production of black/brown eumelanin. Pheomelanin has weak shielding capacity against ultraviolet radiation relative to eumelanin, and has been shown to amplify ultraviolet-A-induced reactive oxygen species. Several observations, however, complicate the assumption that melanoma risk is completely ultraviolet-radiation-dependent. For example, unlike non-melanoma skin cancers, melanoma is not restricted to sun-exposed skin and ultraviolet radiation signature mutations are infrequently oncogenic drivers. Although linkage of melanoma risk to ultraviolet radiation exposure is beyond doubt, ultraviolet-radiation-independent events are likely to have a significant role. Here we introduce a conditional, melanocyte-targeted allele of the most common melanoma oncoprotein, BRAF(V600E), into mice carrying an inactivating mutation in the Mc1r gene (these mice have a phenotype analogous to red hair/fair skin humans). We observed a high incidence of invasive melanomas without providing additional gene aberrations or ultraviolet radiation exposure. To investigate the mechanism of ultraviolet-radiation-independent carcinogenesis, we introduced an albino allele, which ablates all pigment production on the Mc1r(e/e) background. Selective absence of pheomelanin synthesis was protective against melanoma development. In addition, normal Mc1r(e/e) mouse skin was found to have significantly greater oxidative DNA and lipid damage than albino-Mc1r(e/e) mouse skin. These data suggest that the pheomelanin pigment pathway produces ultraviolet-radiation-independent carcinogenic contributions to melanomagenesis by a mechanism of oxidative damage. Although protection from ultraviolet radiation remains important, additional strategies may be required for optimal melanoma prevention.

Label-free DNA imaging in vivo with stimulated Raman scattering microscopy.

Label-free DNA imaging is highly desirable in biology and medicine to perform live imaging without affecting cell function and to obtain instant histological tissue examination during surgical procedures. Here we show a label-free DNA imaging method with stimulated Raman scattering (SRS) microscopy for visualization of the cell nuclei in live animals and intact fresh human tissues with subcellular resolution. Relying on the distinct Raman spectral features of the carbon-hydrogen bonds in DNA, the distribution of DNA is retrieved from the strong background of proteins and lipids by linear decomposition of SRS images at three optimally selected Raman shifts. Based on changes on DNA condensation in the nucleus, we were able to capture chromosome dynamics during cell division both in vitro and in vivo. We tracked mouse skin cell proliferation, induced by drug treatment, through in vivo counting of the mitotic rate. Furthermore, we demonstrated a label-free histology method for human skin cancer diagnosis that provides comparable results to other conventional tissue staining methods such as H&E. Our approach exhibits higher sensitivity than SRS imaging of DNA in the fingerprint spectral region. Compared with spontaneous Raman imaging of DNA, our approach is three orders of magnitude faster, allowing both chromatin dynamic studies and label-free optical histology in real time.

New onset erythematous nodules in an elderly woman.

An 86-year- old woman with a history of recurrent bronchitis and giant cell arteritis presented for new onset, cyclic and migratory erythematous nodules associated with fatigue and weight loss. Although a systemic vasculitis was initially suspected, elevated inflammatory markers and symptoms persisted despite aggressive corticosteroid therapy. Excisional biopsy of one nodule showed dense suppurative and granulomatous inflammation that was rife with acid-fast bacilli. The patient was urgently admitted for empiric treatment of disseminated mycobacterial infection. Although T-SPOT Tuberculosis testing and direct mycobacterial PCR were negative, mass spectrometry demonstrated Mycobacterium chelonae. The patient was treated with a macrolide and quinolone combination regimen and then discharged to a rehabilitation facility.