XTX301, a Tumor-Activated Interleukin-12 Has the Potential to Widen the Therapeutic Index of IL12 Treatment for Solid Tumors as Evidenced by Preclinical Studies.

IL12 is a proinflammatory cytokine, that has shown promising antitumor activity in humans by promoting the recruitment and activation of immune cells in tumors. However, the systemic administration of IL12 has been accompanied by considerable toxicity, prompting interest in researching alternatives to drive preferential IL12 bioactivity in the tumor. Here, we have generated XTX301, a tumor-activated IL12 linked to the human Fc protein via a protease cleavable linker that is pharmacologically inactivated by an IL12 receptor subunit beta 2 masking domain. In vitro characterization demonstrates multiple matrix metalloproteases, as well as human primary tumors cultured as cell suspensions, can effectively activate XTX301. Intravenous administration of a mouse surrogate mXTX301 demonstrated significant tumor growth inhibition (TGI) in inflamed and non-inflamed mouse models without causing systemic toxicities. The superiority of mXTX301 in mediating TGI compared with non-activatable control molecules and the greater percentage of active mXTX301 in tumors versus other organs further confirms activation by the tumor microenvironment-associated proteases in vivo. Pharmacodynamic characterization shows tumor selective increases in inflammation and upregulation of immune-related genes involved in IFNγ cell signaling, antigen processing, presentation, and adaptive immune response. XTX301 was tolerated following four repeat doses up to 2.0 mg/kg in a nonhuman primate study; XTX301 exposures were substantially higher than those at the minimally efficacious dose in mice. Thus, XTX301 has the potential to achieve potent antitumor activity while widening the therapeutic index of IL12 treatment and is currently being evaluated in a phase I clinical trial.

Outcomes of Upper Lip Mohs Surgery Repairs Using Standardized Scar Scales With Particular Emphasis on Vermillion Border Involvement.

BACKGROUND: The lips are a common location for skin cancer, and thus, a common site for Mohs micrographic surgery (MMS). As an important cosmetic and functional facial unit, MMS defects and reconstruction can affect patient perception on functional and aesthetic outcomes. OBJECTIVE: The objective of this study was to compare aesthetic and functional outcomes after upper lip MMS between patients with vermillion sparing repairs (VSR) versus vermillion crossing repairs (VCR). MATERIALS AND METHODS: Patients from a single institution from 2018 to 2022 undergoing MMS of the upper lip with linear or select flap repairs were included. Patients were assessed at a minimum of 6-week follow-up for self-assessment of functional and cosmetic outcomes, as well as physician assessment of scar cosmesis using validated Patient and Observed Scar Assessment Scale and Scar Cosmesis Assessment and Rating scale. The results were compared between VSR and VCR groups. RESULTS: Forty-five patients were included in this study. No significant difference between patient assessment of functional and cosmetic outcome was identified between VSR and VCR. CONCLUSION: Patient satisfaction with lip reconstruction can be high. Crossing the vermillion border does not affect patient assessment of aesthetic and functional results and should be considered if needed to optimize reconstructive outcomes.

Lysine metabolism is a novel metabolic tumor suppressor pathway in breast cancer.

The International Agency for Research on Cancer determined that obesity is the primary preventable cause of breast cancer. The nuclear receptor peroxisome proliferator activated receptor γ (PPARγ) binds inflammatory mediators in obesity and its expression is reduced in human breast cancer. We created a new model to better understand how the obese microenvironment alters nuclear receptor function in breast cancer. The obesity related cancer phenotype was PPARγ dependent; deletion of PPARγ in mammary epithelium which is a tumor suppressor in lean mice unexpectedly increased tumor latency, reduced the luminal progenitor (LP) tumor cell fraction, and increased autophagic and senescent cells. Loss of PPARγ expression in mammary epithelium of obese mice increased expression of 2-aminoadipate semialdehyde synthase (AASS) which regulates lysine catabolism to acetoacetate. PPARγ-associated co-repressors and activators regulated AASS expression via a canonical response element. AASS expression was significantly reduced in human breast cancer, and AASS overexpression or acetoacetate treatment inhibited proliferation and induced autophagy and senescence in human breast cancer cell lines. Genetic or pharmacologic HDAC inhibition promoted autophagy and senescence in mammary tumor cells in vitro and in vivo. We concluded that lysine metabolism is a novel metabolic tumor suppressor pathway in breast cancer.

Mimicking the mimicker: Necrotizing sarcoid granulomatosis.

Necrotizing sarcoid granulomatosis (NSG) is a rare disease that shares similarities with pulmonary vasculitides and sarcoidosis. This is a report of two cases of NSG with a review of literature. The first case is a 33-year-old black female with a one-year history of malaise and cough. Lung imaging revealed scattered pulmonary nodules. Histopathology showed multiple necrotizing granulomas without prominent neutrophilic infiltrates. The second case is a 58-year-old white female with a one-year history of fatigue, dyspnea, and ophthalmoplegia on the left eye. Imaging showed multiple pulmonary nodules. Lung biopsy was consistent with NSG. The challenge of the NSG diagnosis is to distinguish it from other mimickers. Pathology often shows necrotizing granulomatous vasculitis, distinguishing it from classical sarcoid. Laboratory markers for vasculitis like neutrophil cytoplasmic antibodies and antibodies against myeloperoxidase and proteinase 3 are negative or only low titers. NSG responds well to immune-suppression, most commonly with glucocorticoids.

PARP5B is required for nonhomologous end joining during tumorigenesis in vivo.

Poly(ADP-ribose) polymerases (PARP) act as DNA damage sensors that produce poly(ADP-ribose) (PAR) chains at double-strand breaks, facilitating the recruitment of repair factors. Cancers with homologous recombination defects are sensitive to small molecule PARP inhibitors. Despite PARP5B gene copy number changes in many cancers, the effects of this genetic alteration on tumor phenotype are largely unknown. To better understand this clinical finding, we characterized a PARP5B null mutation in a carcinogen-induced in vivo head and neck squamous cell carcinoma (SCC) model. Reduced PARP5B expression inhibited tumor growth, induced primary tumor differentiation and apoptosis, and inhibited cell proliferation and metastasis. Loss of PARP5B expression-induced ataxia telangiectasia and Rad3 related (ATR) activation and depleted the cancer stem cell fraction. PARP5B null tumor cells lacked 53BP1+ double-strand break foci, ATM activation, and p53 induction compared to PARP5B+/+ cancers. PARP5B null SCC expresses a multiprotein complex containing PML, pRPA, Rad50, Rad51, XRCC1, proliferating cell nuclear antigen (PCNA), and Mcm2, suggesting an HR-mediated repair mechanism at DNA replication foci. Low doses of etoposide combined with the PARP5B inhibitor XAV939 induced senescence and apoptosis in human SCC lines. NBS1 overexpression in these cells inhibited the effects of low-dose etoposide/XAV939 treatment. Our results indicate that PARP5B inhibition is new targeted cancer therapy.

DNA Double-strand Break Signaling Is a Therapeutic Target in Head and Neck Cancer.

BACKGROUND: Head and neck cancer (HNC) is common worldwide. Given poor outcomes for patients with HNC, research into targeted therapies is needed. Ataxia telangiectasia mutated (ATM) is a DNA damage kinase which is activated by double-strand DNA breaks. We tested the effects of a novel ATM inhibitor on HNC cell lines and xenografts. MATERIALS AND METHODS: p53-Binding protein 1 and phosphorylated ATM were localized in cultured cells by immunofluorescence microscopy. Protein expression was determined by western blot. Tumor xenografts were established by injecting HNC lines into immunocompromised mice. Tumor sections were characterized by immunohistochemistry. Apoptotic cells were determined by terminal transferase-mediated dUTP nick-end labeling assay. RESULTS: ATM inhibition increased double-strand DNA breaks at replication foci in HNC cell lines. ATM inhibition affected cell-cycle regulatory protein expression, blocked cell-cycle progression at the G2/M phase and resulted in apoptosis. CONCLUSION: ATM inhibition may be therapeutically useful in treating HNC.

New Developments in the Management of Cutaneous Squamous Cell Carcinoma.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. List important prognostic features that affect cutaneous squamous cell carcinoma risk. 2. Summarize the changes to the AJCC Cancer Staging Manual, Eighth Edition, staging system for cutaneous squamous cell carcinoma. 3. Evaluate the draining nodal basin with appropriate imaging modalities. 4. Recommend adjuvant radiation therapy in the correct clinical setting for high-risk tumors. 5. Recognize the currently available treatments for advanced cutaneous squamous cell carcinoma. SUMMARY: This continuing medical education article reviews the features, management, and prognosis of cutaneous squamous cell carcinoma with an emphasis on high-risk squamous cell carcinoma and data from the past 3 years. This review will discuss the primary tumor management, high-risk features of a squamous cell carcinoma, changes to the American Joint Committee on Cancer staging system, and the utility of sentinel lymph node biopsy, and critically review the evidence regarding adjuvant therapy.

Club Cell Heme Oxygenase-1 Deletion: Effects in Hyperoxia-Exposed Adult Mice.

Thioredoxin reductase-1 (TXNRD1) inhibition activates nuclear factor (erythroid-derived 2)-like 2 (Nrf2) responses and prevents acute lung injury (ALI). Heme oxygenase-1 (HO-1) induction following TXNRD1 inhibition is Nrf2-dependent in airway epithelial (club) cells in vitro. The influence of club cell HO-1 on lung development and lung injury responses is poorly understood. The present studies characterized the effects of hyperoxia on club cell-specific HO-1 knockout (KO) mice. These mice were generated by crossing Hmox1 flox mice with transgenic mice expressing cre recombinase under control of the club cell-specific Scgb1a1 promoter. Baseline analyses of lung architecture and function performed in age-matched adult wild-type and KO mice indicated an increased alveolar size and airway resistance in HO-1 KO mice. In subsequent experiments, adult wild-type and HO-1 KO mice were either continuously exposed to >95% hyperoxia or room air for 72 h or exposed to >95 hyperoxia for 48 h followed by recovery in room air for 48 h. Injury was quantitatively assessed by calculating right lung/body weight ratios (g/kg). Analyses indicated an independent effect of hyperoxia but not genotype on right lung/body weight ratios in both wild-type and HO-1 KO mice. The magnitude of increases in right lung/body weight ratios was similar in mice of both genotypes. In the recovery model, an independent effect of hyperoxia but not genotype was also detected. In contrast to the continuous exposure model, right lung/body weight ratio mice were significantly elevated in HO-1 KO but not wild-type mice. Though club cell HO-1 does not alter hyperoxic sensitivity in adult mice, it significantly influences lung development and resolution of lung injury following acute hyperoxic exposure.

Telomere DNA Damage Signaling Regulates Prostate Cancer Tumorigenesis.

Telomere shortening has been demonstrated in benign prostatic hypertrophy (BPH), which is associated with prostate epithelial cell senescence. Telomere shortening is the most frequently observed genetic alteration in prostatic intraepithelial neoplasia, and is associated with poor clinical outcomes in prostate cancer. Gene expression database analysis revealed decreased TRF2 expression during malignant progression of the prostate gland. We reasoned that reduced TRF2 expression in prostate epithelium, by activating the telomere DNA damage response, would allow us to model both benign and malignant prostate disease. Prostate glands with reduced epithelial TRF2 expression developed age- and p53-dependent hypertrophy, senescence, ductal dilation, and smooth muscle hyperplasia similar to human BPH. Prostate tumors with reduced TRF2 expression were classified as high-grade androgen receptor-negative adenocarcinomas, which exhibited decreased latency, increased proliferation, and distant metastases. Prostate cancer stem cells with reduced TRF2 expression were highly tumorigenic and maintained telomeres both by telomerase and alternative lengthening (ALT). Telomerase inhibition in prostate glands with reduced TRF2 expression produced significant reduction in prostate tumor incidence by halting progression at intraepithelial neoplasia (PIN). These lesions were highly differentiated, exhibited low proliferation index, and high apoptotic cell fraction. Prostate tumors with reduced TRF2 expression and telomerase inhibition failed to metastasize and did not exhibit ALT. IMPLICATIONS: Our results demonstrate that the telomere DNA damage response regulates BPH, PIN, and prostate cancer and may be therapeutically manipulated to prevent prostate cancer progression.

Extracellular nucleic acid scavenging rescues rats from sulfur mustard analog-induced lung injury and mortality.

Sulfur mustard (SM) is a highly toxic war chemical that causes significant morbidity and mortality and lacks any effective therapy. Rats exposed to aerosolized CEES (2-chloroethyl ethyl sulfide; 10% in ethanol), an analog of SM, developed acute respiratory distress syndrome (ARDS), which is characterized by increased inflammation, hypoxemia and impaired gas exchange. We observed elevated levels of extracellular nucleic acids (eNA) in the bronchoalveolar lavage fluid (BALF) of CEES-exposed animals. eNA can induce inflammation, coagulation and barrier dysfunction. Treatment with hexadimethrine bromide (HDMBr; 10 mg/kg), an eNA neutralizing agent, 2 h post-exposure, reduced lung injury, inhibited disruption of alveolar-capillary barrier, improved blood oxygenation (PaO2/FiO2 ratio), thus reversing ARDS symptoms. HDMBr treatment also reduced lung inflammation in the CEES-exposed animals by decreasing IL-6, IL-1A, CXCL-1 and CCL-2 mRNA levels in lung tissues and HMGB1 protein in BALF. Furthermore, HDMBr treatment also reduced levels of lung tissue factor and plasminogen activator inhibitor-1 indicating reduction in clot formation and increased fibrinolysis. Fibrin was reduced in BALF of the HDMBr-treated animals. This was further confirmed by histology that revealed diminished airway fibrin, epithelial sloughing and hyaline membrane in the lungs of HDMBr-treated animals. HDMBr completely rescued the CEES-associated mortality 12 h post-exposure when the survival rate in CEES-only group was just 50%. Experimental eNA treatment of cells caused increased inflammation that was reversed by HDMBr. These results demonstrate a role of eNA in the pathogenesis of CEES/SM-induced injury and that its neutralization can serve as a potential therapeutic approach in treating SM toxicity.

Mohs Surgery for SEER Registry-Captured Melanoma In Situ and Rare Cutaneous Tumors: Comparing National Utilization Patterns Before and After Implementation of the Affordable Care Act (2010) and Appropriate Use Criteria (2012).

BACKGROUND: The Affordable Care Act (ACA) and the appropriate use criteria (AUC) for Mohs micrographic surgery (MMS) had the potential to increase utilization rates of MMS for indicated skin cancers, but it is unknown whether this has occurred. OBJECTIVE: To determine whether rates of MMS utilization for head and neck melanoma in situ (MIS) and rare cutaneous tumors (RCTs) increased after the implementation of the ACA and AUC publication. MATERIALS AND METHODS: Retrospective review using data from the SEER database. Melanoma in situ and RCT tumor cases from before and after the ACA and AUC publication were compared. RESULTS: Twenty-four thousand six hundred seventy-eight cases were analyzed. Mohs micrographic surgery utilization for MIS decreased from 13.9% before the ACA to 12.3% after the ACA (odds ratio 0.87; p = .012). There was no significant change in MMS utilization for MIS after publication of the AUC. There was also no significant change in MMS utilization for treatment of RCT after the ACA or AUC publication. Stratification of patients into age groups younger or older than 65 years did not change utilization rates. CONCLUSION: Rates of MMS for treatment of MIS and RCT have not increased since the advent of the ACA or AUC. This finding highlights the need for continued efforts to improve access to MMS and to increase education of its utility in treating skin cancer.

Prognostic Factors, Treatment, and Survival in Primary Cutaneous Mucinous Carcinoma: A SEER Database Analysis.

BACKGROUND: Limited information exists on the demographics, tumor characteristics, and treatment in primary cutaneous mucinous carcinoma (PCMC). OBJECTIVE: The authors sought to describe prognostic factors, incidence rates, and the subsequent primary malignancy (SPM) risk in patients with PCMC. METHODS: Primary cutaneous mucinous carcinoma cases in the National Cancer Institute's Surveillance, Epidemiology, and End Results data (1972-2013) were analyzed to provide demographic, cancer-related, and treatment information and to calculate incidence and mortality. Patients were stratified by stage (local, regional, distant disease) for comparison. The risk of developing an SPM was calculated. RESULTS: Four hundred eleven PCMC cases were identified. The age-adjusted incidence was 0.04 cases per 100,000-person years. Blacks were disproportionately affected by PCMC (0.048; 95% confidence interval, 0.034-0.065; p < .001). Approximately 67.4% of patients had local disease, 10.5% had regional disease, and 5.8% had distant disease. Primary cutaneous mucinous carcinoma-specific mortality was independent of sex, age, race, primary site, histologic tumor grade, tumor size, tumor stage, or treatment. The overall frequency of developing a second primary malignancy was not increased in patients with PCMC. CONCLUSION: Although PCMC occurs with equally in both sexes, it may be more common in African Americans than previously recognized. Although eyelid PCMC may have a higher rate of distant metastasis, all patients need close follow-up.

Paracrine Interaction of Cancer Stem Cell Populations Is Regulated by the Senescence-Associated Secretory Phenotype (SASP).

Dyskeratosis congenita is a telomere DNA damage syndrome characterized by defective telomere maintenance, bone marrow failure, and increased head and neck cancer risk. The Pot1b-/-;Terc+/- mouse exhibits some features of dyskeratosis congenita, but head and neck cancer was not reported in this model. To model the head and neck cancer phenotype, we created unique Pot1b- and p53-null-mutant models which allow genetic lineage tracing of two distinct stem cell populations. Loss of Pot1b expression depleted stem cells via ATR/Chk1/p53 signaling. Tumorigenesis was inhibited in Pot1b-/-;p53+/+ mice due to cellular senescence. Pot1b-/-;p53-/- tumors also exhibited senescence, but proliferated and metastasized with expansion of Lgr6+ stem cells indicative of senescence-associated secretory phenotype. Selective depletion of the small K15+ stem cell fraction resulted in reduction of Lgr6+ cells and inhibition of tumorigenesis via senescence. Gene expression studies revealed that K15+ cancer stem cells regulate Lgr6+ cancer stem cell expansion via chemokine signaling. Genetic ablation of the chemokine receptor Cxcr2 inhibited cancer stem cell expansion and tumorigenesis via senescence. The effects of chemokines were primarily mediated by PI3K signaling, which is a therapeutic target in head and neck cancer. IMPLICATIONS: Paracrine interactions of cancer stem cell populations impact therapeutic options and patient outcomes.

Molecular and cellular basis of mammary gland fibrosis and cancer risk.

Mammary gland luminal cells are maintained by the proliferation of ER- luminal progenitor (LP) cells. Human breast LP cells exhibit telomere DNA damage, which is associated with mammographic density and increased cancer risk. Telomeric repeat factor 2 (TRF2) protects telomeres from DNA damage response. TRF2 expression is reduced in human breast cancers. We deleted TRF2 expression in mammary gland epithelium. Mammary glands lacking TRF2 expression exhibited increased telomere DNA damage response, histopathological and functional degeneration, and prominent ductal fibrosis. TRF2-deficient mammary tumors exhibited rapid onset and increased proliferation. Tumor derived LP cells failed to form tumors after transplantation. The MSC population was highly tumorigenic and maintained telomeres via the ALT mechanism. Telomere DNA damage response in mammary tumors resulted in p53 dependent ER+ cellular differentiation and sensitivity to anti-estrogen therapy. Our results provide a new in vivo model of mammographic density, stem cell differentiation, cancer risk, and therapeutic sensitivity.

Acquired widespread lymphangiectasia mimicking immunobullous disease: A case report.

A 76-year-old Caucasian woman presented with a 3-year history of a recurrent pruritic eruption on the hips, thighs, and under the breasts associated with intermittent lesions resembling vesicles and bullae that failed to respond to topical corticosteroids. She had a history of severe lichen sclerosis et atrophicus, leading to invasive squamous cell carcinoma of the vulva for which she underwent radical vulvectomy and bilateral inguino-femoral lymph node dissection. On physical examination, involving the inframammary breasts, abdomen, hips, and proximal thighs there were multiple erosions with hemorrhagic crust and multiple clustered translucent papules. 4+ pitting and nonpitting edema were present on both legs. Biopsies were consistent with acquired lymphangiectasia. Acquired lymphangiectasia can be difficult to identify clinically. In our case, the unusually widespread distribution was morphologically reminiscent of immunobullous disease. The extensive surgical disruption to the patient's lymphatic system was likely responsible for this unique presentation.

Incidentally detected ectopic thyroid in juxta cardiac location-Imaging and pathology.

Ectopic thyroid gland is a developmental anomaly that results from the arrest of thyroid tissue along its path of descent from the floor of mouth to the pre tracheal position in the lower neck. It is typically found along the thyroglossal duct with the base of the tongue being the most common site. Apart from mediastinal extension of goiter, the incidence of true intrathoracic ectopic thyroid tissue is rare. Presence of ectopic thyroid has been reported not only in the chest but also in the abdomen and pelvis. Pericardial and intracardiac locations are extremely uncommon and right ventricle location is predominant among the described cases. We describe a case of incidentally detected ectopic thyroid tissue in a rarer location-adjacent to the left atrium. The patient, who had undergone a nephrectomy for renal oncocytoma 5 years ago, presented with unintentional weight loss and left sided flank pain, prompting a workup to rule out abdominal malignancy. Findings on the computed tomography (CT) scan of the abdomen and pelvis prompted further investigation including a chest CT which showed a heterogeneously enhancing mass near the left atrium. Given its location, further radiological investigations played an important role in eliminating the differential diagnosis of paraganglioma. The mass was surgically resected and discovered to be a hyperplastic thyroid nodule on histologic examination.

Telomere DNA damage signaling regulates cancer stem cell evolution, epithelial mesenchymal transition, and metastasis.

Chromosome ends are protected by telomeres that prevent DNA damage response and degradation. When telomeres become critically short, the DNA damage response is activated at chromosome ends which induces cellular senescence or apoptosis. Telomeres are protected by the double stranded DNA binding protein TRF2 and maintained by telomerase or a recombination based mechanism known as alternative lengthening of telomeres (ALT). Telomerase is expressed in the basal layer of the epidermis, and stem cells in epidermis have longer telomeres than proliferating populations. Stem cell expansion has been associated with epithelial-mesenchymal transition (EMT) in cancer. EMT is a critical process in cancer progression in which cells acquire spindle morphology, migrate from the primary tumor, and spread to distant anatomic sites. Our previous study demonstrated that loss of TRF2 expression observed in human squamous cell carcinomas expanded metastatic cancer stem cells during mouse skin carcinogenesis. To determine if telomerase inhibition could block the TRF2-null mediated expansion of metastatic clones, we characterized skin carcinogenesis in a conditional TRF2/Terc double null mutant mouse. Loss of TRF2 and Terc expression resulted in telomere DNA damage, severely depleted CD34 + and Lgr6+ cancer stem cells, and induced terminal differentiation of metastatic cancer cells. However a novel cancer stem cell population evolved in primary tumors exhibiting genomic instability, ALT, and EMT. Surprisingly we discovered that metastatic clones evolved prior to histopathologic onset of primary tumors. These results have important implications for understanding the evolution and treatment of metastatic cancer.

The histone methyltransferase EZH2 promotes mammary stem and luminal progenitor cell expansion, metastasis and inhibits estrogen receptor-positive cellular differentiation in a model of basal breast cancer.

Mammary stem cells (MSCs) are the progenitor population for human breast epithelia. MSCs give rise during mammary gland development to estrogen receptor (ER)-negative basal cells and the ER- luminal progenitor (LP) population which maintains ER+ and ER- luminal cells. The MSC population is expanded and tumorigenic in some mouse mammary cancer models, and these tumor-initiating cells have been isolated from human breast cancers. MSC expansion is associated with aggressive biological behavior in human breast cancer. The LP population is tumorigenic in some mouse mammary cancer models, and is the progenitor population of basal breast cancer in humans. The enhancer of zeste homolog 2 (EZH2) is a methyltransferase which catalyzes lysine 27 methylation in histone H3 resulting in suppression of target gene expression. The histone demethylase JMJD3 opposes the activity of EZH2 by demethylating histone H3 lysine 27. EZH2 is a member of the polycomb group of proteins which regulates cell type identity. EZH2 expression was found to be increased in histologically normal human breast tissue among women with high breast cancer risk, and was elevated in ductal hyperplasia and ductal carcinoma in situ. EZH2 overexpression is associated with poorly differentiated and aggressive breast cancer in humans. However, the mechanisms by which EZH2 results in increased breast cancer risk and aggressive tumors are not completely characterized. Using in vivo transplantation of mammary cancer stem cells transduced with EZH2 or JMJD3 shRNAs, we demonstrated that EZH2 promotes mammary stem and LP cell expansion, metastasis and inhibits ER-positive cellular differentiation.

Pigmented Mammary Paget Disease Mimicking Superficial Spreading Melanoma in an Elderly African-American Female.

BACKGROUND: Pigmented mammary Paget disease (PMPD) is a rare disease that may mimic cutaneous melanoma both in clinical presentation and on histology. OBJECTIVE: The goal of this study was to discuss the clinical and histologic similarities between PMPD and cutaneous melanoma and how to differentiate between the two diseases. METHODS: We describe an African-American patient with PMPD who was thought to have cutaneous melanoma on presentation. We describe the similarities of PMPD to cutaneous melanoma both clinically and on histology and discuss the methods of differentiation. RESULTS: Clinical examination revealed a large pigmented patch of the left breast that appeared asymmetrical with irregular borders with a highly variable color pattern throughout. Histologic evaluation showed characteristics shared between PMPD and cutaneous melanoma. Immunohistochemical staining was needed for differentiation. CONCLUSION: PMPD is a rare disease and is similar in clinical presentation and on histology to cutaneous melanoma. Immunohistochemical staining must be used to differentiate between the two diseases.