Sebaceous gland atrophy due to seborrheic dermatitis in a patient with alopecia: A potential pitfall.

Seborrheic dermatitis is an inflammatory condition that usually presents with erythema, scaly greasy papules, and plaques affecting sebaceous gland-rich areas and predominantly involving the face and scalp. The diagnosis of seborrheic dermatitis can often be rendered based on the clinical presentation. However, in certain cases, a biopsy can be useful to distinguish it from clinical mimics such as psoriasis, discoid lupus, and rosacea. Prominent sebaceous gland atrophy without scarring has been well-described as an important and relatively specific clue for psoriatic or drug-induced alopecia. However, sebaceous gland atrophy is not specific to psoriasis and has been demonstrated in seborrheic dermatitis, facial discoid dermatitis, and potentially may occur in other inflammatory dermatoses of the scalp. We report a 23-year-old female patient presenting with non-scarring hair loss and histopathological findings demonstrating mild androgenetic alopecia and changes of seborrheic dermatitis with dramatic sebaceous gland atrophy. The patient had no history or evidence of psoriasis clinically. Our case suggests that in patients with seborrheic dermatitis, sebaceous gland atrophy may complicate the evaluation of alopecia biopsies and should be recognized as a pitfall. Seborrheic dermatitis should be included in the differential diagnosis of alopecia biopsies showing prominent sebaceous gland atrophy.

HPV-associated Vulvar Intraepithelial Carcinoma With Sebaceous Differentiation: Report of 2 Cases.

Sebaceous carcinoma (SC) is a malignant neoplasm demonstrating sebocytic differentiation, commonly in the periocular area. Sebocytic differentiation is recognized by multivesicular cytoplasmic clearing with frequent nuclear scalloping. The vesicles can be highlighted by immunohistochemical stains against the perilipin family proteins including adipophilin. Extraocular SC is uncommon but well reported, often in the setting of Muir-Torre syndrome; however, vulvar SC is exceptionally rare. The literature review yielded only 12 prior cases of vulvar SC, all of which showed invasion. Here we report 2 additional similar cases from 2 different institutions of an intraepithelial carcinoma with sebaceous differentiation. Histologic examination of multiple specimens from both patients showed similar features: a multifocal intraepithelial basaloid nodular neoplasm sparing the basal layer with occasional pagetoid spread. The tumor cells demonstrated a high nuclear to cytoplasmic ratio, mitoses, variably foamy vacuolated cytoplasm, and nuclear indentation. Multiple specimens from both patients showed evidence of sebaceous differentiation (substantiated by adipophilin positivity in a membranous vesicular pattern in case 1 and by androgen receptor and epithelial membrane antigen positivity in case 2), and squamous differentiation (substantiated by p63/p40 and weak CK 5/6 expression), as well as human papillomavirus (HPV) association (substantiated by p16 block positivity and detection of high-risk HPV by in situ hybridization). One case was a true in situ lesion without evidence of invasion, and the other case was predominantly an in situ carcinoma with prominent adnexal extension and focal superficial invasion of <1 mm seen in one of multiple specimens. To our knowledge, these 2 cases are the first to show a vulvar SC/carcinoma with sebaceous differentiation that is predominantly limited to the epidermis, and the first documentation of HPV infection in vulvar sebaceous neoplasms. Vulvar intraepithelial carcinoma with sebaceous differentiation is the umbrella term we chose for this entity. Whether this is a true SC in situ that is HPV positive/driven, or a vulvar intraepithelial neoplasia with sebaceous differentiation, is not entirely clear. We emphasize the importance of looking for this morphology to avoid misclassification. Due to the rarity of cases, optimal treatment at this site has not been established.

Demographics and perceptions of diversity in dermatopathology workforce and training environments in the United States.

OBJECTIVES: The aim of this study was to determine the demographics and perceptions of diversity, equity, and inclusion (DEI) in the field of dermatopathology to provide a measurable baseline for future efforts to enhance equity measures within our subspecialty. METHODS: A questionnaire based on a previously validated instrument by Association of American Medical Colleges (AAMC) was sent to American Society of Dermatopathology (ASDP) members to collect the demographic information (gender, race, sexual orientation, disability, experience and practice setting, etc.) and evaluate eight diversity, engagement, and inclusivity statements on a 1-5 Likert scale. RESULTS: The demographics of 207 of 1331 (15%) respondents showed slight male predominance. Eleven percent of respondents identified as LGBTQI. The major racial distribution was comprised of 62% White, 18% Asian (including Middle Eastern/Indian), 10% Hispanic, and 4% Black respondents. New-in-practice respondents (those in practice-5 years or less) were more likely to have a pathology background (71% vs. 56%, p = 0.047) than their more-established peers with more than 5 years of service. This trend also contributed to increased diversity in terms of gender (66% females) and race (48% non-White) among the newer generation. Dermatology-trained dermatopathologists were mostly White (70%) and male (53%). Analysis of respondent demographics with perception statements showed that White and US graduate respondents (compared to other groups) were more likely to have a positive perception about DEI within the field of dermatopathology. CONCLUSIONS: The results provide a snapshot of the current state of diversity within the field of dermatopathology. Moreover, these results highlight opportunities for further increasing diversity in general and leadership in particular within dermatopathology.

Bilateral eyelid swelling as the presenting sign of subcutaneous sarcoidosis.

An 18-year-old Black female presented with a 2-year history of bilateral upper eyelid swelling and the recent onset of multiple subcutaneous nodules on the arms. She had previously undergone evaluation and treatment for presumed angioedema. Biopsies of the eyelid and an arm nodule demonstrated non-necrotizing granulomatous inflammation with special stains negative for acid-fast bacilli and fungi, and the patient was diagnosed with subcutaneous sarcoidosis. The isolated finding of bilateral eyelid swelling 2 years prior to the onset of additional cutaneous findings led to a significant delay in diagnosis, highlighting the importance of considering sarcoidosis in the differential diagnosis for bilateral eyelid swelling.

Blue nevus with smooth muscle hyperplasia: A rare hamartoma.

A limited number of distinct histopathological variants of blue nevus exist, and hamartomatous proliferations involving melanocytic components, dendritic, or otherwise, have also been described. Blue nevus/smooth muscle hamartomas represent a rarely described entity. In this paper, we add two examples of this unusual hamartoma to the existing literature. These additional blue nevus/smooth muscle hamartomas occurred on the left mid-upper back of a 50-year-old woman and the central upper back of a 54-year-old man. Both lesions were clinically atypical pigmented lesions. Histopathologic review of both specimens revealed proliferations of predominantly spindled and pigmented dermal melanocytes with associated smooth muscle hyperplasia, compatible with blue nevus/smooth muscle hamartoma. Both specimens were accompanied by subtle changes suggesting follicular induction, a phenomenon previously described as occurring in a minority of specimens. A brief re-examination of recently diagnosed blue nevus at our institution did not reveal any additional cases in which a subtle smooth muscle component had been missed, suggesting this type of hamartoma is, indeed, exceedingly rare.

Dermatofibrosarcoma protuberans with platelet-derived growth factor-D rearrangement; two cases with morphologically distinct presentations.

Dermatofibrosarcoma protuberans (DFSP) is a mesenchymal neoplasm that is usually located in the dermis or subcutis and is locally aggressive. Rarely, these lesions may undergo fibrosarcomatous transformation, which is thought to increase their metastatic potential. DFSP is classically associated with a 17;22 translocation (or ring chromosome thereof) resulting in fusion of the COL1A1 and PDGFB genes. However, variant fusions involving PDGFD have been recently reported. Herein, we present two morphologically diverse cases of DFSP with PDGFD rearrangement. Case 1 is a 68-year-old female with a left dorsal foot lesion. Morphologically, the lesion is unusual as it is a well-circumscribed, hypercellular, subcutaneous nodule with uniform CD34-positive spindle cells arranged in a herringbone pattern without storiform arrangement or "honeycombing" fat entrapment. It was diagnosed as pure fibrosarcomatous DFSP. Case 2 is a 37-year-old male with a right supra-auricular lesion. Morphologically, the lesion displays classic DFSP features including bland CD34-positive spindle cells with storiform growth, fat entrapment, and infiltrative borders. Both lesions were negative for COL1A1-PDGFB fusion but positive for PDGFD rearrangement by fluorescence in situ hybridization (FISH) analysis. FISH testing for PDGFD rearrangement should be performed in cases where there is a high suspicion for DFSP but initial studies for COL1A1-PDGFB are negative.

Appropriate use criteria for ancillary diagnostic testing in dermatopathology: New recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology Appropriate Use Criteria Committee.

BACKGROUND: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. METHODS: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. RESULTS: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." LIMITATIONS: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. CONCLUSIONS: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

Primary Cutaneous Alveolar Rhabdomyosarcoma in an Elderly Adult: A Rare Potential Mimic of Merkel Cell Carcinoma.

ABSTRACT: Rhabdomyosarcoma (RMS) rarely arises as a primary skin tumor. It is also very rare in older adults, especially the alveolar type. We report an 80-year-old White woman who presented with a painful, erythematous, raised lesion (2 × 3.5 cm) above the left knee that was fixed within the skin, yet mobile about underlying soft tissue. A punch biopsy showed monotonous malignant round blue cells involving the dermis. Immunostains showed diffuse expression of CD56, focal chromogranin, focal dot-like pancytokeratin, CK7, and neurofilament, but negative for synaptophysin, CK20, SOX-10, MUM-1, CD43, TTF-1, and CD99. A CK20-negative variant of Merkel cell carcinoma was initially favored, but given the unusual immunophenotype and the presence of cellular dyscohesion, desmin and myogenin stains were performed, both of which were diffusely positive. Molecular testing revealed rearrangement of PAX3 and FOXO1 loci, confirming the diagnosis of alveolar RMS. PET/CT showed a probable 1.9-cm left inguinal lymph node metastasis; no internal or deep soft tissue primary tumor mass was identified, supporting a true primary cutaneous origin. Alveolar RMS may express keratins and neuroendocrine markers, making it easy to confuse with Merkel cell carcinoma on those exceptionally rare instances, when it arises in the skin of older adults.

Cervical dysplasia in a patient with inherited epidermodysplasia verruciformis-A mere coincidence?

Epidermodysplasia verruciformis (EV) is a rare inherited or acquired genodermatosis caused by increased susceptibility to infection by the beta subtypes of human papillomavirus (HPV). The co-occurrence of EV with high-risk (HR) HPV infection leading to cervical dysplasia is unreported in the literature to date. We report a patient with inherited EV who developed extensive anogenital and cervical dysplasia linked to concurrent HR-HPV infection. Literature review suggests that there is a negative correlation of cervical dysplasia and cervical cancer with EV, which suggests that this patient's presentation and course are exceptional.

Dermal melanocytic tumor with CRTC1-TRIM11 fusion: Report of two additional cases with review of the literature of an emerging entity.

"Cutaneous melanocytic tumor with CRTC1-TRIM11 fusion" (CMTCT) is a newly described, potentially novel entity that typically presents as a dermal nodule on the head and neck, extremities, and trunk of adults. Histopathologically, it is reported as a nodular or multinodular tumor composed of epithelioid and spindle cells that are variably immunoreactive for S100-protein, SOX10, and MITF along with more specific melanocytic markers such as MelanA and HMB45. With only 11 cases reported in the English literature so far, the neoplasm appears to behave in a relatively indolent fashion. Nevertheless, in one case, local recurrence and synchronous distant metastasis were evident after 13 years. Additional cases with longer follow-up are essential to determine the neoplasm's biologic behavior with more accuracy. Herein, two cases of CMTCT, one arising on the lower back of a 65-year-old female and the other on the arm of a 33-year-old female in addition to a comprehensive literature review are reported.

Lichenoid dermatoses involving the vulva: A clinical-pathologic correlation✰.

The lichenoid tissue reaction pattern generally signifies cytotoxic damage to the epithelium. When such reaction pattern occurs on vulvar skin or mucosa, the effects can result in considerable morbidity. None of the entities discussed in this review are entirely unique to the vulva, however, some entities may classically occur at this site, while others tend to be widespread diseases that may incidentally affect vulvar skin and mucosa. Given the complex anatomy of the vulva and the bridging of a site showing both keratinizing squamous epithelium and non-keratinizing squamous mucosa, histopathologic features may display variation in presentation. Although identification of a "lichenoid reaction pattern" alone may provide insight into the disease process, understanding of clinical presentation and specific sites of involvement, along with recognition of the nuanced features of the disease entities can help establish a specific diagnosis. Accurate histopathologic diagnoses by pathologists can improve the ability for treating clinicians to implement timely and effective treatment.

Characterization of Morphologic and Cytochemical Staining Properties of Exogenous Materials Mimicking Fungal Organisms Encountered in Skin Biopsies.

BACKGROUND: Exogenous materials may be encountered in skin biopsies as contamination. Contamination may occur during the biopsy procedure in the clinic or during tissue processing in the laboratory. Although the experienced pathologist may often instinctively ignore clear examples of contamination, such tissue may be a source of confusion for young pathologists and those in training. Foreign materials can typically be recognized as exogenous by morphology, polarizability, and the presence or absence of a tissue reaction, but we have rarely encountered situations in which exogenous materials could be misinterpreted as organisms, either by their morphologic appearance or staining properties. METHODS: Exogenous materials used during skin biopsy and grossing were embedded in a nonhuman tissue scaffold and prepared into histologic slides. Hematoxylin and eosin (H&E), periodic acid-Schiff with diastase, and Grocott methenamine silver stains were performed, and each material was evaluated under polarized microscopy. RESULTS: Exogenous materials were divided into the following 3 categories with shared morphologic appearances and staining properties: suture materials, plant-based materials, and synthetic materials. CONCLUSION: We present a comprehensive characterization of the morphologic and cytochemical staining properties of multiple exogenous materials that may contaminate a skin biopsy. This characterization will aid the pathologist by providing a mechanism to identify potential contaminants in skin biopsies.

Elastophagocytosis and interstitial granulomatous infiltrate are more common in extragenital vs genital lichen sclerosus.

BACKGROUND: Genital and extragenital lichen sclerosus (LS) share similar histopathologic features. A recent small series documented elastophagocytosis uniquely in extragenital LS. We evaluated a larger series of LS for elastophagocytosis, elastic fiber loss, and other histopathologic features. We evaluated matrix metalloproteinase (MMP) expression to determine if these proteins play an etiologic role. METHODS: Genital (n = 42) and extragenital (n = 41) LS biopsies were examined for histopathologic features, elastic fiber alteration (Verhoeff van Gieson staining), and MMP-2 and MMP-9 expression (immunohistochemistry). RESULTS: Elastophagocytosis and an interstitial granulomatous pattern were significantly more common in extragenital LS than genital LS (43.9% vs 4.7% and 56.1% vs 9.5%). Extragenital LS had mild/focal elastic fiber loss (43.9%), while genital LS had moderate (61.9%) or marked (19%) loss. MMP-9 was diffusely expressed in histiocytes in both types of LS (genital 97.5%; extragenital 100%). Weak MMP-2 expression was seen in genital (58%) and extragenital (55%) LS. CONCLUSIONS: Extragenital LS, but not genital LS, frequently exhibits elastophagocytosis and interstitial granulomatous infiltrate, and these patterns could contribute to elastic fiber destruction in extragenital LS. While MMP-2 and MMP-9 expression are common in LS, expression did not significantly differ depending on anatomic site and thus is unlikely to explain observed histopathologic differences.

PAS and GMS utility in dermatopathology: Review of the current medical literature.

The American Society of Dermatopathology has established an Appropriate Use Criteria (AUC) Committee with the intention of establishing evidence-based recommendations regarding the appropriateness of various ancillary tests commonly utilized by dermatopathologists. Periodic acid Schiff (PAS) and Grocott (or Gomori) methenamine silver (GMS) stains represent some of the most commonly employed ancillary tests in dermatopathology. The utility of these tests was targeted for evaluation by the AUC. This literature review represents a comprehensive evaluation of available evidence for the utility of PAS and/or GMS staining of skin and nail biopsies. In concert with expert opinion, these data will be incorporated into future recommendations by the AUC for PAS and GMS staining in routine dermatopathology practice.

Cutaneous pleomorphic fibromas arising in patients with germline TP53 mutations.

Pleomorphic fibromas are rare benign cutaneous neoplasms associated with deletion/loss of chromosomes 13q and 17p, where RB1 and TP53 are located, respectively. Herein, we report five cases of pleomorphic fibroma arising in patients with germline TP53 mutations, suggesting a potential link with Li-Fraumeni syndrome. All three patients were female and young (mean age 27) with a strong personal and/or family oncologic history and confirmed pathogenic germline TP53 mutations. In two patients, multiple pleomorphic fibromas were diagnosed. Clinically, the lesions arose at various cutaneous sites and were small (≤2 cm) and raised (4/5). Histopathologically, the tumors were paucicellular, composed of atypical spindled to stellate cells with hyperchromatic and variably pleomorphic nuclei. Mitotic activity was exceedingly low, although rare atypical mitotic figures were seen in one case. Immunohistochemically, the tumor cells were diffusely positive for p16 (3/3) and showed loss of Rb expression (5/5). All cases showed aberrant p53 expression (overexpression in 4, complete loss in 1). The tumors have followed a benign clinical course with no evidence of progression or recurrence. In conclusion, the development of multiple pleomorphic fibromas in a young patient may be a clue to an underlying genetic cancer syndrome involving TP53.

Epithelioid Fibrous Histiocytoma With Dot-Like Perinuclear ALK Expression and PRKAR2A-ALK Fusion.

Epithelioid fibrous histiocytoma (EFH) is a rare, benign, cutaneous neoplasm. This fibrohistiocytic tumor was once believed to be a variant of fibrous histiocytoma, but EFH is now known to be a distinct entity based on the presence of ALK gene rearrangements in most cases. The pattern of immunohistochemical expression of ALK in EFH in the literature thus far describes both granular cytoplasmic staining and nuclear staining. We present a case of EFH with dot-like Golgi pattern perinuclear ALK expression, a previously undescribed staining pattern. We surmised this unique staining pattern could be due to a novel fusion partner, and using FISH, we confirmed a rearrangement of the ALK (2p23) locus. Further investigation with whole transcriptome sequencing led to the discovery of PRKAR2A-ALK fusion, and the function of this fusion partner reflects a Golgi-predominant localization of the protein. Attention to the distinct immunohistochemical pattern of ALK expression may provide clues to the function of the fusion partner.

Hansen Disease (Leprosy) and Armadillo Exposure in Arkansas: A Case Series.

BACKGROUND: Although most cases of Hansen disease (HD) in the United States are imported from endemic areas, a subset of cases are relate to exposure to nine-banded armadillos. Several recent cases of HD in Arkansas occurred in patients who had not traveled to endemic areas and who reported variable degrees of armadillo exposure. OBJECTIVE: The purpose of this study was to report 6 cases of HD diagnosed in Arkansas between 2004 and 2016. The secondary purpose was to explore the correlation between exposure to the nine-banded armadillo as it pertains to transmission of the disease. METHODS: The referring clinician of each patient was contacted to gather information regarding the patient's clinical presentation, armadillo exposure, and travel history. In addition, the Arkansas Department of Health was consulted to review the demographics of individuals diagnosed with HD in the past 15 years and to review the distribution of HD throughout the state of Arkansas. RESULTS: Six domestic cases of HD were associated with both direct and indirect exposure to armadillos. LIMITATIONS: Armadillo exposure may be underreported in patients with HD because of fear of stigmatization and/or lack of access to care. CONCLUSIONS: Direct exposure to armadillos does not appear to be required for transmission of HD making a soil-mediated mechanism of indirect exposure plausible.

Colliding, colonizing or combining? Four cases illustrating the unique challenges presented by melanoma arising in conjunction with basal cell carcinoma.

Biphasic lesions comprised of melanocytic and epithelial components are rare entities believed to arise either as a collision of 2 histologically distinct lesions in the same anatomic location or as a singular progenitor tumor differentiating along 2 differing lineages. Regardless of mechanism of origin, these tumors present unique challenges in pathologic interpretation and in determining appropriate measurements, which assigns subsequent prognosis to the patient. We present 4 tumors of melanoma co-existing with basal cell carcinoma (BCC) and discuss relevant literature regarding these biphasic entities. Patients consisted of 3 males and 1 female, ranging in age from 62 to 93, with lesions located on the shoulder, frontal scalp, forearm and nose. Three of 4 lesions showed melanoma cells limited to BCC tumor lobules, without evidence of direct dermal invasion by melanoma cells, raising the question of whether or not these tumors should be classified as in situ or invasive melanoma. These cases highlight the complexity that such lesions pose to dermatopathologists, in terms of their uncertain origin and variable microscopic appearance. In the absence of data regarding outcomes for these tumors (given their rarity), it is important to utilize a case-by-case approach, with careful clinical correlation and appropriate use of ancillary techniques.

Metastatic laryngeal large cell neuroendocrine carcinoma: A rare case of presentation and extreme tumor burden.

Large cell neuroendocrine carcinoma (LCNEC) of the larynx is an aggressive form of neuroendocrine carcinoma that affects smokers at an average age of 60 years. LCNEC is characterized by large cells with round to ovoid nuclei distributed in a trabecular or nested growth pattern. Previously, laryngeal LCNEC and atypical carcinoid tumors were considered identical; however, laryngeal LCNEC has been shown to have higher mitotic rates and worse prognosis, which has led to laryngeal LCNEC's being separated from atypical carcinoid and classified as a poorly differentiated neuroendocrine carcinoma in the most recent World Health Organization classification. We present a case of a 56-year-old female who presented with painful subcutaneous skin lesions that were diagnosed as metastatic carcinoma at an outside facility. Subsequent workup revealed a primary epiglottic lesion. Over the next 4 years, she continued to develop over 100 similar subcutaneous nodules. Additional workup confirmed neuroendocrine differentiation, thus clarifying the diagnosis of metastatic LCNEC. Review of literature has revealed only 1 reported case of LCNEC with skin metastasis. This is the first reported case in which skin metastasis was the initial presenting symptom; moreover, our case is unique with regard to the heavy metastatic burden to the skin.

Quantitative Histone Mass Spectrometry Identifies Elevated Histone H3 Lysine 27 (Lys27) Trimethylation in Melanoma.

Normal cell growth is characterized by a regulated epigenetic program that drives cellular activities such as gene transcription, DNA replication, and DNA damage repair. Perturbation of this epigenetic program can lead to events such as mis-regulation of gene transcription and diseases such as cancer. To begin to understand the epigenetic program correlated to the development of melanoma, we performed a novel quantitative mass spectrometric analysis of histone post-translational modifications mis-regulated in melanoma cell culture as well as patient tumors. Aggressive melanoma cell lines as well as metastatic melanoma were found to have elevated histone H3 Lys(27) trimethylation (H3K27me3) accompanied by overexpressed methyltransferase EZH2 that adds the specific modification. The altered epigenetic program that led to elevated H3K27me3 in melanoma cell culture was found to directly silence transcription of the tumor suppressor genes RUNX3 and E-cadherin. The EZH2-mediated silencing of RUNX3 and E-cadherin transcription was also validated in advanced stage human melanoma tissues. This is the first study focusing on the detailed epigenetic mechanisms leading to EZH2-mediated silencing of RUNX3 and E-cadherin tumor suppressors in melanoma. This study underscores the utility of using high resolution mass spectrometry to identify mis-regulated epigenetic programs in diseases such as cancer, which could ultimately lead to the identification of biological markers for diagnostic and prognostic applications.