Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/chemistry , Receptors, LDL/analysis , Skin Neoplasms/chemistry , Age Factors , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/secondary , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neurons/pathology , Pilot Projects , Prognosis , Skin Neoplasms/pathology , Up-RegulationABSTRACT
ABSTRACT: The presence of neoplastic melanocytes within the eccrine apparatus into the reticular dermis and/or subcutaneous tissue is extremely rare. The staging of syringotropic melanomas and their biological behavior are still controversial. We present 6 new cases of syringotropic melanoma and their main histopathologic features; review the previous literature; and discuss about the origin, staging, and prognosis of this rare variant of melanoma.
Subject(s)
Melanocytes/pathology , Melanoma/pathology , Skin Neoplasms/pathology , Sweat Glands/pathology , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Biopsy , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Male , Melanocytes/chemistry , Melanoma/chemistry , Melanoma/surgery , Middle Aged , Predictive Value of Tests , Skin Neoplasms/chemistry , Skin Neoplasms/surgery , Sweat Glands/chemistry , Sweat Glands/surgery , Treatment OutcomeABSTRACT
BACKGROUND: Melanoma is a highly malignant tumor with diverse histopathological morphology and frequent aberrant expression of immunohistochemical markers. An occasionally reported phenomenon is the abnormal expression of neuroendocrine markers. Awareness of this situation is essential because such tumors need to be differentiated from neuroendocrine tumors because of their significant therapeutic and prognostic implications. METHODS: We retrospectively analyzed the expression of chromogranin A (CgA), synaptophysin (Syn) and CD56 as neuroendocrine markers in 308 cases with melanomas. Kaplan-Meier curves and Cox regression analyses were used for overall survival (OS) and progression-free survival (PFS) evaluation and comparison between neuroendocrine markers expression status in all melanoma cases or stage I-II cases. RESULTS: The expression of neuroendocrine markers in melanomas is not uncommon. CgA was positive in 6/304 (2.0%) cases, Syn in 26/304 (8.6%), and CD56 in 56/189 (29.6%). None of the cases co-expressed all the three markers. Focal or weak expression of at least one neuroendocrine marker was identified in 70/188 (37.2%) cases. The expression of CgA was correlated with age (p = 0.019), while the positive expression of Syn and CD56 showed borderline significance (p = 0.078 and 0.083, respectively), but not for any neuroendocrine marker expression. The expression of any neuroendocrine marker showed borderline significance with staging (p = 0.066). The expression of CgA, Syn, CD56, or any neuroendocrine marker did not correlate with clinicopathological features including sex, specimen type, origin, location, and histology subtype. Survival analyses revealed that the expression of neuroendocrine markers was not associated with OS or PFS. CONCLUSIONS: Our study confirms that neuroendocrine marker expression is a common phenomenon in melanomas, but it has no prognostic significance. Nevertheless, awareness can avoid misdiagnosis in cases of melanomas with unusual morphology and immunophenotypes.
Subject(s)
Biomarkers, Tumor/analysis , Immunohistochemistry , Melanoma/chemistry , Neuroendocrine Tumors/chemistry , Skin Neoplasms/chemistry , Adolescent , Adult , Aged , Aged, 80 and over , CD56 Antigen/analysis , Child , Chromogranin A/analysis , Diagnostic Errors , Female , Humans , Male , Melanoma/mortality , Melanoma/pathology , Melanoma/therapy , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Progression-Free Survival , Retrospective Studies , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Synaptophysin/analysis , Time Factors , Young AdultABSTRACT
The term "cutaneous lymphadenoma" was coined in this journal for an unusual lymphoepithelial cutaneous adnexal neoplasm, possibly with immature pilosebaceous differentiation. Some authors further proposed that cutaneous lymphadenoma was an adamantinoid trichoblastoma. However, although a hair follicle differentiation is widely accepted, the fact that this is a lymphoepithelial tumor is not appropriately explained by the trichoblastoma hypothesis. Our goal was to further clarify the phenotypic and genotypic features of cutaneous lymphadenoma in a series of 11 cases. Histologically, a lobular architecture surrounded by a dense fibrous stroma was present in all cases. The lobules were composed of epithelial cells admixtured with small lymphocytes and isolated or clustered large Reed-Sternberg-like (RS-L) cells. The epithelial cells were diffusely positive for the hair follicle stem cell markers CK15, PHLDA1, and for androgen receptor. No immunostaining for markers of sebaceous differentiation was found. Intraepithelial lymphocytes were predominantly CD3+, CD4+, FoxP3+ T cells. RS-L cells showed both strong Jagged-1 and Notch1 cytoplasmic immunostaining. Androgen-regulated NKX3.1 nuclear immunostaining was present in a subset of large intralobular cells in all cases. Double immunostaining showed coexpression of NKX3.1 and CD30 in a subset of RS-L cells. No immunostaining for lymphocytic or epithelial markers was present in RS-L cells. EGFR, PIK3CA, and FGFR3 somatic mutations were found by next-generation sequencing in 56% of the cases. We consider that cutaneous lymphadenoma is a distinct benign lymphoepithelial tumor with androgen receptor and hair follicle bulge stem cell marker expression, RS-L cell-derived Notch1 ligand, and common EGFR gene mutations.
Subject(s)
Adenolymphoma , Biomarkers, Tumor , Epithelial Cells , Hair Follicle , Mutation , Receptor, Notch1/analysis , Receptors, Androgen/analysis , Reed-Sternberg Cells , Skin Neoplasms , Adenolymphoma/chemistry , Adenolymphoma/genetics , Adenolymphoma/immunology , Adenolymphoma/pathology , Adult , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , DNA Mutational Analysis , Epithelial Cells/chemistry , Epithelial Cells/pathology , ErbB Receptors/genetics , Female , Hair Follicle/chemistry , Hair Follicle/immunology , Hair Follicle/pathology , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry , Lymphocytes, Tumor-Infiltrating/immunology , Male , Middle Aged , Reed-Sternberg Cells/chemistry , Reed-Sternberg Cells/pathology , Skin Neoplasms/chemistry , Skin Neoplasms/genetics , Skin Neoplasms/immunology , Skin Neoplasms/pathology , T-Lymphocytes, Regulatory/immunologyABSTRACT
A new 11 amino acid linear peptide named roseabol A (1) and the known compound 13-oxo-trans-9,10-epoxy-11(E)-octadecenoic acid (2) were isolated from the fungus Clonostachys rosea. Combined NMR and MS analysis revealed that roseabol A (1) contained amino acid residues characteristic of the peptaibol family of peptides such as isovaline, α-aminoisobutyric acid, hydroxyproline, leucinol, and an N-terminal isovaleric acid moiety. The amino acid sequence was established by a combination of NMR studies and tandem MS fragmentation analyses, and the absolute configurations of the constituent amino acids of 1 were determined by the advanced Marfey's method. Compound 2 showed inhibitory activity against Merkel cell carcinoma, a rare and difficult-to-treat type of skin cancer, with an IC50 value of 16.5 µM.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Merkel Cell/drug therapy , Hypocreales/chemistry , Peptaibols/chemistry , Peptaibols/pharmacology , Skin Neoplasms/drug therapy , Amino Acid Sequence , Antineoplastic Agents/chemistry , Carcinoma, Merkel Cell/chemistry , Carcinoma, Merkel Cell/metabolism , Cell Line, Tumor , Humans , Magnetic Resonance Spectroscopy/methods , Molecular Structure , Skin Neoplasms/chemistry , Skin Neoplasms/metabolismABSTRACT
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin. The cell of origin of MCC is thus far unknown and proposed cells of origin include Merkel cells, pro-/pre- or pre-B cells, epithelial stem cells, and dermal stem cells. In this study, we aimed to shed further light on the possibility that a subset of MCC tumors arise from epithelial stem cells of the skin by examining the expression of hair follicle and epidermal stem cell markers in MCC and normal human skin. We also aimed to elucidate any correlation between the expression of these markers and tumor Merkel cell polyomavirus (MCPyV) status or other clinicopathological characteristics or patient survival. Expression of CK19, SOX9, LGR5, and LRIG1 in MCC and normal human skin was studied by immunohistochemistry, and the staining patterns or intensities were statistically correlated with patient, tumor, MCPyV, and survival parameters. In a cohort of 137 cases of MCC, we observed dot-like immunoexpression of CK19 in 30 cases (22.1%) and homogeneous expression in 103 cases (75.7%). We also observed positive immunoexpression of SOX9 in 21 cases (15.3%), LGR5 in 118 cases (86.1%), and LRIG1 in 117 cases (86.0%). Immunoexpression of LRIG1 was found to correlate with better overall and MCC-specific survival. We observed frequent immunoexpression of several hair follicle and epidermal stem cell markers in MCC and found LRIG1 to be a positive prognostic marker in MCC.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Merkel Cell/chemistry , Epithelial Cells/chemistry , Membrane Glycoproteins/analysis , Neoplastic Stem Cells/chemistry , Skin Neoplasms/chemistry , Adult , Aged , Aged, 80 and over , Carcinoma, Merkel Cell/mortality , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/therapy , Epithelial Cells/pathology , Female , Humans , Immunohistochemistry , Keratin-19/analysis , Male , Middle Aged , Neoplastic Stem Cells/pathology , Phenotype , Prognosis , Receptors, G-Protein-Coupled/analysis , SOX9 Transcription Factor/analysis , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Skin Neoplasms/therapyABSTRACT
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.
Subject(s)
B7-H1 Antigen/biosynthesis , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Merkel Cell/mortality , Indoleamine-Pyrrole 2,3,-Dioxygenase/biosynthesis , Lymphocytes, Tumor-Infiltrating/immunology , Neoplasm Proteins/biosynthesis , Skin Neoplasms/mortality , T-Lymphocyte Subsets/immunology , Adaptive Immunity , Age Factors , Aged , Aged, 80 and over , Biomarkers, Tumor , CD8-Positive T-Lymphocytes/chemistry , Carcinoma, Merkel Cell/chemistry , Carcinoma, Merkel Cell/immunology , Carcinoma, Merkel Cell/virology , Female , Forkhead Transcription Factors/analysis , Head and Neck Neoplasms/chemistry , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/virology , Humans , Kaplan-Meier Estimate , Lymphocyte Count , Male , Merkel cell polyomavirus/isolation & purification , Middle Aged , Multivariate Analysis , Neoplasm Staging , Neoplasms, Second Primary/chemistry , Neoplasms, Second Primary/immunology , Neoplasms, Second Primary/mortality , Neoplasms, Second Primary/virology , Prognosis , Progression-Free Survival , Proportional Hazards Models , Sex Factors , Skin Neoplasms/chemistry , Skin Neoplasms/immunology , Skin Neoplasms/virology , Skin Ulcer/etiology , Tumor Virus InfectionsABSTRACT
Hereditary leiomyomatosis (HL) is a rare autosomal dominant syndrome resulting from a mutation in the germline of the fumarate hydratase (FH) gene. Patients with this syndrome have an increased risk of cutaneous and uterine smooth muscle tumors as well as renal cancer. Renal carcinoma associated with hereditary leiomyomatosis (HLRCC) was recognized as a subtype of independent renal tumor in the 2016 WHO classification. We present a case of HLRCC occurring in a 39-year-old man with no family history or specific skin manifestations at the time of diagnosis.
Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Leiomyomatosis/pathology , Neoplastic Syndromes, Hereditary/pathology , Skin Neoplasms/pathology , Uterine Neoplasms/pathology , Adult , Carcinoma, Renal Cell/chemistry , Carcinoma, Renal Cell/genetics , Humans , Kidney Neoplasms/chemistry , Kidney Neoplasms/genetics , Leiomyomatosis/chemistry , Leiomyomatosis/genetics , Male , Neoplastic Syndromes, Hereditary/genetics , Skin Neoplasms/chemistry , Skin Neoplasms/genetics , Uterine Neoplasms/chemistry , Uterine Neoplasms/geneticsABSTRACT
Melanoma is a common, highly fatal skin cancer. Photoacoustic imaging can achieve highly sensitive and high-contrast detection of melanin molecules in tissues, also inheriting the high penetration depth and high spatial resolution characteristics of ultrasound imaging, thus it is a very promising non-invasive diagnostic tool for early melanoma. In this work, we built an acoustic-resolution-based photoacoustic microscopy system, using 1064 nm/532 nm pulsed light to observe melanoma in the back of a mouse with simultaneous photoacoustic/ultrasound imaging. Through the fusion of multi-modal images, accurate positioning of melanoma and its surrounding normal tissues were realized. This work will further promote the application of photoacoustic imaging in the clinical diagnosis of early melanoma.
Subject(s)
Melanoma/diagnostic imaging , Multimodal Imaging/methods , Photoacoustic Techniques/methods , Skin Neoplasms/diagnostic imaging , Ultrasonography/methods , Animals , Early Detection of Cancer/methods , Melanins/analysis , Melanoma/chemistry , Melanoma/pathology , Metals , Mice , Mice, Inbred C57BL , Phantoms, Imaging , Skin Neoplasms/chemistry , Skin Neoplasms/pathologySubject(s)
Cell Differentiation , Hamartoma/pathology , Nevus, Pigmented/pathology , Skin Neoplasms/pathology , Adult , Biomarkers, Tumor/analysis , Biopsy , Diagnosis, Differential , Female , Hamartoma/chemistry , Hamartoma/surgery , Humans , Immunohistochemistry , Nevus, Pigmented/chemistry , Predictive Value of Tests , Skin Neoplasms/chemistry , Skin Neoplasms/surgeryABSTRACT
BACKGROUND: Giant congenital melanocytic nevi (GCMN) treatment remains controversial. While surgical resection is the best option for complete removal, skin shortage to reconstruct the skin defect remains an issue. We report a novel treatment using a high hydrostatic pressurization (HHP) technique and a cryopreservation procedure. However, cryopreservation may inhibit revascularization of implanted nevus tissue and cultured epidermal autograft (CEA) take. We aimed to investigate the influence of the cryopreservation procedure on the HHP-treated dermis specimen and CEA take on cryopreserved tissue. METHODS: Nevus tissue harvested from a patient with GCMN was inactivated with HHP of 200 MPa and then cryopreserved at -30°C for 28 days. The cryopreserved specimen was compared with fresh (HHP-treated without cryopreservation) tissue and with untreated (without HHP treatment) tissue to evaluate the extracellular matrix, basal membranes, and capillaries. Cultured epidermis (CE) take on the cryopreserved tissue was evaluated following implantation of the cryopreserved nevus tissue with CE into the subcutis of nude mice. RESULTS: No difference was observed between cryopreserved and fresh tissue in terms of collagen or elastic fibers, dermal capillaries, or basement membranes at the epidermal-dermal junction. In 4 of 6 samples (67%), applied CE took on the nevus tissues and regenerated the epidermis in the cryopreserved group compared with 5 of 6 samples (83%) in the fresh group. CONCLUSION: Cryopreservation at -30°C for 28 days did not result in significant damage to inactivated nevus tissue, and applied CE on the cryopreserved nevus tissues took and regenerated the epidermis. Inactivated nevus tissue with HHP can be used as a dermal substitute after 28-day cryopreservation.
Subject(s)
Cryopreservation , Dermis , Nevus/chemistry , Skin Neoplasms/chemistry , Skin, Artificial , Animals , Humans , Hydrostatic Pressure , Male , Mice , Mice, NudeABSTRACT
Mycosis fungoides with large cell transformation (MFLCT) can be difficult to distinguish from primary cutaneous CD30+ T cell lymphoproliferative disorders (PC CD30+ LPD), especially primary cutaneous anaplastic large cell lymphoma (PC-ALCL). This diagnostic distinction is critical for appropriate patient management. GATA3 has been proposed to be useful in the discrimination between these two entities. We identified 25 cases of MFLCT and 24 cases of PC CD30+ LPDs (including lymphomatoid papulosis (n=14), PC-ALCL (n=6), and CD30+ LPD, not otherwise specified (n=4)) diagnosed at our institution from 2002 to 2019. Sections from archived specimens were stained to evaluate for GATA3 expression by immunohistochemistry and compared among cutaneous CD30+ T cell LPDs. The majority of the MFLCT cohort had strong, diffuse expression of GATA3 ranging from 0 to 100% of dermal T cells (mean 53.20%) with 15/25 cases (60%) showing GATA3 expression greater than 50%, while the PC CD30+ LPD group showed variable, moderate GATA3 labeling ranging from 0 to 60% of dermal T cells (mean 23.26%), with 5/6 cases (83%) showing GATA3 expression less than 40% (p =0.003). The calculated sensitivity and specificity were 56% and 74%, while positive and negative predictive values were 70% and 61%, respectively. Based on the percent staining of positive cells, using 50% as a cutoff value for expression, GATA3 might be a useful immunohistochemical marker to discriminate MFLCT from PC CD30+ LPDs, including PC-ALCL.
Subject(s)
Biomarkers, Tumor/analysis , GATA3 Transcription Factor/analysis , Immunohistochemistry , Ki-1 Antigen/analysis , Lymphoma, Large-Cell, Anaplastic/chemistry , Lymphomatoid Papulosis/metabolism , Mycosis Fungoides/chemistry , Skin Neoplasms/chemistry , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Lymphoma, Large-Cell, Anaplastic/immunology , Lymphoma, Large-Cell, Anaplastic/pathology , Lymphomatoid Papulosis/immunology , Lymphomatoid Papulosis/pathology , Male , Middle Aged , Mycosis Fungoides/immunology , Mycosis Fungoides/pathology , Predictive Value of Tests , Retrospective Studies , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Young AdultABSTRACT
ABSTRACT: Eosinophilic hyaline inclusions (EHIs) or globules have been reported in various cutaneous tumors including vascular lesions, myoepithelial neoplasms, and basal cell carcinoma. In basal cell carcinoma, the presence of intracytoplasmic inclusions is reportedly associated with myoepithelial differentiation. In this regard, EHI has not been conclusively documented in a cutaneous lesion of genuine squamous cell lineage without aberrant differentiation. In the current case, a biopsy from the right thigh of a 71-year-old male patient demonstrated a relatively well-demarcated intraepidermal squamous lesion featured an admixture of predominantly enlarged keratinocytes harboring distinct eccentric intracytoplasmic EHI and a smaller population of keratinocytes displaying pale cytoplasm. Cytologic atypia, mitotic activity, and inflammatory cells were not identified. The intracytoplasmic EHI stained red with Masson's trichrome and were negative with periodic-acid Schiff with and without diastase. Immunologically, the lesion was strongly and diffusely positive for various cytokeratins but negative for ubiquitin and myoepithelial markers. Only cytokeratin AE1 revealed a differential staining pattern as the suprabasal lesional cells displayed significantly stronger immunoreactivity in comparison with the adjacent normal keratinocytes. Polymerase chain reaction for low-risk and high-risk human papillomavirus was negative. Molecular studies did not reveal any mutations commonly encountered in seborrheic or lichenoid keratoses. As an analogous lesion has not previously reported in the literature, the term hyaline inclusion acanthoma is proposed for this peculiar lesion.
Subject(s)
Acanthoma/chemistry , Biomarkers, Tumor/analysis , Hyalin , Keratinocytes/chemistry , Skin Neoplasms/chemistry , Acanthoma/pathology , Aged , Biopsy , Humans , Immunohistochemistry , Keratinocytes/pathology , Male , Skin Neoplasms/pathologyABSTRACT
PURPOSE: To date there has not been an extensive analysis of the outcomes of biomarker use in oncology. METHODS: Data were pooled across four indications in oncology drawing upon trial outcomes from www.clinicaltrials.gov: breast cancer, non-small cell lung cancer (NSCLC), melanoma and colorectal cancer from 1998 to 2017. We compared the likelihood drugs would progress through the stages of clinical trial testing to approval based on biomarker status. This was done with multi-state Markov models, tools that describe the stochastic process in which subjects move among a finite number of states. RESULTS: Over 10000 trials were screened, which yielded 745 drugs. The inclusion of biomarker status as a covariate significantly improved the fit of the Markov model in describing the drug trajectories through clinical trial testing stages. Hazard ratios based on the Markov models revealed the likelihood of drug approval with biomarkers having nearly a fivefold increase for all indications combined. A 12, 8 and 7-fold hazard ratio was observed for breast cancer, melanoma and NSCLC, respectively. Markov models with exploratory biomarkers outperformed Markov models with no biomarkers. CONCLUSION: This is the first systematic statistical evidence that biomarkers clearly increase clinical trial success rates in three different indications in oncology. Also, exploratory biomarkers, long before they are properly validated, appear to improve success rates in oncology. This supports early and aggressive adoption of biomarkers in oncology clinical trials.
Subject(s)
Antineoplastic Agents/therapeutic use , Biomarkers, Tumor , Clinical Trials as Topic , Drug Approval , Markov Chains , Neoplasms/drug therapy , Biomarkers, Tumor/classification , Biomarkers, Tumor/genetics , Breast Neoplasms/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/chemistry , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Clinical Trials as Topic/classification , Clinical Trials as Topic/statistics & numerical data , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Colorectal Neoplasms/chemistry , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Databases, Factual/statistics & numerical data , Drug Approval/methods , Drug Approval/statistics & numerical data , Female , Genetic Markers , Humans , Lung Neoplasms/chemistry , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Medical Oncology , Melanoma/chemistry , Melanoma/drug therapy , Melanoma/genetics , Neoplasms/chemistry , Neoplasms/genetics , Risk , Skin Neoplasms/chemistry , Skin Neoplasms/drug therapy , Skin Neoplasms/genetics , Stochastic Processes , Time Factors , Treatment FailureABSTRACT
Nanospray desorption electrospray ionization mass spectrometry is an ambient ionization technique that is capable of mapping proteins in tissue sections. However, high-abundant molecules or isobaric interference in biological samples hampers its broad applications in probing low-abundant proteins. To address this challenge, herein we demonstrated an integrated module that coupled pneumatic-assisted nanospray desorption electrospray ionization mass spectrometry with high-field asymmetric ion mobility spectrometry. Using this module to analyze mouse brain sections, the protein coverage was significantly increased. This improvement allowed the mapping of low-abundant proteins in tissue sections with a 5 µm spatial resolution enabled by computationally assisted fusion with optical microscopic images. Moreover, the module was successfully applied to characterize melanoma in skin tissues based on the enhanced protein profiles. The results suggested that this integrating module will be potentially applied to discover novel proteins in cancers.
Subject(s)
Ion Mobility Spectrometry/instrumentation , Neoplasms/diagnosis , Proteins/analysis , Spectrometry, Mass, Electrospray Ionization/instrumentation , Animals , Humans , Melanoma/chemistry , Melanoma/diagnosis , Mice , Molecular Imaging/methods , Neoplasms/chemistry , Skin Neoplasms/chemistry , Skin Neoplasms/diagnosisSubject(s)
Melanoma/diagnosis , Melanoma/surgery , Skin Neoplasms/diagnosis , Skin Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Eosine Yellowish-(YS) , Female , Fluorescent Dyes , Frozen Sections , Hematoxylin , Humans , MART-1 Antigen/analysis , Male , Margins of Excision , Melanoma/chemistry , Middle Aged , Mohs Surgery , Prospective Studies , Sensitivity and Specificity , Skin Neoplasms/chemistry , Tissue FixationABSTRACT
BACKGROUND: Folliculotropic mycosis fungoides (FMF) is a variant of cutaneous T-cell lymphoma that has clinical overlap with a variety of inflammatory follicular unit disorders. However, we describe distinctive presentations of FMF with acneiform features that can be diagnostically challenging, leading to diagnostic delay. OBJECTIVE: To highlight the importance of histopathologic and immunohistochemical evaluation for diagnostic confirmation of presumed inflammatory follicular unit-based disorders that are unusual in presentation or unresponsive to standard therapies. METHODS: A cross-sectional retrospective study of 5 consecutive patients with a histopathologic diagnosis of FMF was conducted. The clinical, histopathologic, immunophenotypic, and molecular genetic features of cases are presented. RESULTS: We describe 5 patients with clinical and histopathologic presentations of FMF masquerading as hidradenitis suppurativa, furunculosis, or acne vulgaris (age range 34-66 years, 4:1 female to male). Clinical morphologies included open and closed comedones, inflammatory pustules, papules and nodules, follicular papules with keratotic plugging, cysts, and scarring involving the face, trunk, and intertriginous areas. All patients failed to respond to standard therapies, including topical and oral antibiotics, topical and oral retinoids, or topical corticosteroids, before receiving the diagnosis of FMF. Lesional skin biopsies showed a perifollicular CD4-positive T-lymphocytic infiltrate with pilotropism, intrafollicular mucin deposition, foreign-body granulomatous inflammation, acute inflammation, and follicular epithelial necrosis. None had concurrent systemic mycosis fungoides. LIMITATIONS: Small retrospective cohort study. CONCLUSION: We present these cases to expand the clinical and histopathologic spectrum of FMF that may strikingly resemble acneiform disorders and to highlight the importance of diagnostic reconsideration with histopathologic evaluation.
Subject(s)
Acne Vulgaris/pathology , Hair Follicle/pathology , Mycosis Fungoides/pathology , Skin Neoplasms/pathology , Adult , Aged , Biomarkers, Tumor/analysis , Biopsy , Cross-Sectional Studies , Diagnosis, Differential , Female , Hair Follicle/chemistry , Humans , Immunohistochemistry , Male , Middle Aged , Mycosis Fungoides/chemistry , Mycosis Fungoides/therapy , Neoplasm Staging , Predictive Value of Tests , Retrospective Studies , Skin Neoplasms/chemistry , Skin Neoplasms/therapyABSTRACT
ABSTRACT: In skin containing hair follicles, specialized epithelial structures known as "touch domes (TDs)" are located where the Merkel cells are clustered. We explored the histogenetic relationship between intraepidermal and dermal Merkel cell carcinomas (MCCs) and investigated which transformed progenitor cells can develop into intraepidermal MCC. We encountered an association between an extremely rare case of dermal and intraepidermal MCC with squamous cell carcinoma, which was examined using standard immunohistochemical methods with various epithelial, neuroendocrine, and TD markers including several immunohistochemical markers. Differential expression levels of CK20 and CD56 were found between intraepidermal and dermal MCCs, indicating molecularly distinct MCC populations. CK15 and CK17, expressed in TDs, were partially expressed in the intraepidermal neuroendocrine component at the tumor periphery in intraepidermal MCC with squamous cell carcinoma. These differences may suggest that the origin of dermal and intraepidermal MCCs is different under pathological conditions. We hypothesize that intraepidermal MCC is derived from tissue-specific stem cells localized within TDs.