ABSTRACT
Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility1. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helper T (TH2) cells within a distinct microanatomical niche. TH2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as TH2-interacting fascial fibroblasts (TIFFs), which expand in response to TH2 cytokines to form subcutaneous fibrous bands. Activation of the TH2-TIFF niche due to neonatal inflammation primes the skin for altered reparative responses to wounding. Furthermore, we identify fibroblasts in healthy human skin that express the TIFF transcriptional signature and detect these cells at high levels in eosinophilic fasciitis, an orphan disease characterized by inflammation and fibrosis of the skin fascia. Taken together, these data define a previously unidentified TH2 cell niche in skin and functionally characterize a disease-associated fibroblast population. The results also suggest a mechanism of immunological priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells to establish an immunological set-point in tissues that is maintained throughout life.
Subject(s)
Fibroblasts/cytology , Inflammation/pathology , Skin/cytology , Stem Cell Niche , Th2 Cells/cytology , Animals , Animals, Newborn , Cytokines/immunology , Eosinophilia/pathology , Fasciitis/pathology , Fibrosis/pathology , Health , Humans , Interleukin-13 Receptor alpha1 Subunit/metabolism , Male , Mice , Skin/pathology , T-Lymphocytes, Regulatory/cytology , Wound HealingABSTRACT
NRAS activating mutations are prevalent in melanocytic neoplasia, occurring in a subset of common acquired melanocytic nevi and â¼30% of cutaneous melanomas. In this study, we described a cohort of 7 distinctive melanocytic tumors characterized by activating point mutations in codon 61 of NRAS with amplification of the mutant NRAS allele and shared clinicopathologic features. These tumors occurred predominantly in younger patients, with a median age of 20 years (range, 6-56 years). They presented as papules on the helix of the ear (4 cases) or extremities (3 cases). Microscopically, the tumors were cellular, relatively well-circumscribed, compound, or intradermal proliferations. The tumor cells often extended into the deep reticular dermis and involved the superficial subcutaneous fat in some cases. The melanocytes were epithelioid to spindled with moderate amounts of cytoplasm and conspicuous nucleoli. They were arranged in short plexiform fascicles, nests, and cords. Some cases had occasional pleomorphic and multinucleated melanocytes. Rare dermal mitotic figures were present in all cases. The dermis contained thick collagen bundles and minimal solar elastosis. Follow-up data were available for 5 patients, with a median period of 4.2 years (range, 1-9 years), during which no recurrences or metastases were reported. Our series highlights a clinicopathologically and molecularly distinctive subset of NRAS-mutated tumors with amplification of the mutant NRAS allele.
Subject(s)
GTP Phosphohydrolases , Membrane Proteins , Nevus, Epithelioid and Spindle Cell , Skin Neoplasms , Humans , GTP Phosphohydrolases/genetics , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Male , Female , Middle Aged , Membrane Proteins/genetics , Adult , Adolescent , Child , Young Adult , Nevus, Epithelioid and Spindle Cell/genetics , Nevus, Epithelioid and Spindle Cell/pathology , Melanoma/genetics , Melanoma/pathology , Gene Amplification , Melanocytes/pathology , Mutation , Nevus, Pigmented/genetics , Nevus, Pigmented/pathology , Point MutationABSTRACT
ABSTRACT: Microsecretory adenocarcinoma (MSA) was first described in 2019 as a low-grade salivary gland neoplasm of intraoral origin with distinct histopathologic features and a characteristic MEF2C::SS18 fusion. Recently, skin was also identified as a primary site for MSA in a report by Bishop et al. Due to its rarity and resemblance to other adnexal tumors, MSA is a challenging diagnosis. Herein, we present a case of cutaneous MSA that was unique for the presence of a significant microcystic component and marked adnexal hyperplasia, which mimicked myxoid microcystic adnexal carcinoma (MAC). A 58-year-old presented with a 1 year history of an enlarging eyelid nodule. Histopathologic analysis revealed dermal tumor composed of small tubules containing inspissated bluish mucinous material. Accompanying marked adnexal hyperplasia and many microcysts were also present. Tumor cells expressed S100 protein, which is distinct from MAC, while p63 immunohistochemistry showed marked loss of myoepithelial labeling, as is common in primary adenocarcinomas. Next generation gene sequencing detected the characteristic MSA fusion protein MEF2c::SS18. We report a novel presentation of MSA that simulated MAC because of the presence of associated microcystic change. The presence of S100 immunopositivity and the identification of MEF2C::SS18 fusion confirmed the diagnosis of cutaneous MSA.
ABSTRACT
BACKGROUND: mRNA SARS-CoV-2 vaccines are administered to 2 million individuals per day in the United States under US Food and Drug Administration emergency use authorization. METHODS: Observational cohort study of hospital employees who received their first SARS-CoV-2 mRNA vaccination between 14 December 2020 and 8 January 2021, including employees who reported onset of an injection site reaction ≥48 hours after administration of their first or second dose to an employee hotline. RESULTS: Thirteen female employees who received the mRNA-1273 vaccine (Moderna) during the first 3 weeks of the SARS-CoV-2 vaccine rollout at San Francisco General Hospital reported a pruritic rash at the injection site appearing 3 -9 days after receipt of their initial dose. Five had milder or similar reactions with earlier onset after the second dose. One additional female employee reported this delayed reaction only after the second dose. None reported serious adverse events or had symptoms severe enough to seek medical attention. These cases represented 1.1% of the 1275 female employees who received their first mRNA-1273 dose and 2.0% of the 557 who were aged 31 -45 years during this initial vaccine rollout. None of 675 males who initiated mRNA-1273 or 3612 employees of any sex who initiated BNT162b (Pfizer) vaccination during this period reported delayed-onset reactions. CONCLUSIONS: These results suggest that delayed-onset, injection site pruritic rashes after mRNA-1273 SARS-CoV-2 vaccine administration, lasting up to 1 week, occur commonly in females, do not lead to serious sequela, and should not deter receipt of the second vaccine dose.
Subject(s)
2019-nCoV Vaccine mRNA-1273 , COVID-19 , Injection Site Reaction/epidemiology , 2019-nCoV Vaccine mRNA-1273/adverse effects , Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Cohort Studies , Female , Hospitals , Humans , Incidence , Male , Middle Aged , SARS-CoV-2 , United States/epidemiologyABSTRACT
BACKGROUND: Spindle cell lipomas, pleomorphic lipomas (SCL/PLs), and pleomorphic fibromas (PF) are tumors with loss of retinoblastoma (RB). The latest World Health Organization classification includes a category of atypical spindle cell/pleomorphic lipomatous tumors (ASPLT), which encompasses tumors in this spectrum that show atypical histopathologic features. We have observed PFs that show similar atypical features. METHODS: Cases of SCL/PL and PF with atypical features were collected from tissue archives between 2010 and 2019. Genetic alterations were investigated using array comparative genomic hybridization (aCGH). RESULT: Of 15 cases found, most tumors were dermal based with fibrocytic or fibroadipocytic appearance and occasional lipoblasts. All cases had a high proliferation index with atypical mitotic figures in 71% of cases. Chromosome 13q loss was present in all cases with CGH data. Additional recurrent chromosomal losses included 17p, 16q, 17q, 20p, 4, and 10. No recurrence was found in limited follow-up. CONCLUSIONS: ASPLTs are characterized by loss of RB, prominent nuclear pleomorphism, mitotic activity including atypical mitotic figures, and genomic instability with multiple chromosomal aberrations. A similar group of tumors with these histopathologic features lacks lipomatous differentiation, and we propose the diagnosis of atypical PF as a fibromatous variant of ASPLT. Limited clinical follow-up appears benign.
Subject(s)
Fibroma , Lipoma , Liposarcoma , Retinal Neoplasms , Retinoblastoma , Skin Neoplasms , Biomarkers, Tumor/genetics , Comparative Genomic Hybridization , Fibroma/genetics , Humans , Lipoma/genetics , Lipoma/pathology , Liposarcoma/pathology , Skin Neoplasms/pathologyABSTRACT
A 72-year-old male presented with scarring alopecia on the scalp vertex, multiple crusted plaques on the hairline, and a history of vesicular eruption on the face. The scalp showed crusted plaques with loss of follicular ostia. No follicular pustules or compound follicles were present. An initial transverse scalp biopsy showed perifollicular neutrophils, lymphocytes, and plasma cells along with dermal fibrosis. Focal epidermal/dermal and follicular/adventitial dermal clefts were apparent but were thought to be secondary to fibrosis, and the biopsy result was interpreted to represent a neutrophil-mediated cicatricial alopecia. Concurrently, direct immunofluorescence (DIF) analysis showed linear junctional deposition of IgG and C3. A repeat scalp biopsy revealed more prominent epidermal/dermal clefts, fibrosis, mixed infiltrate with neutrophils, lymphocytes, histiocytes, and plasma cells, as well as prominent follicular/adventitial dermal clefts with perifollicular neutrophils. Given the combination of clefts, perijunctional neutrophils, and positive DIF findings, it became clear that this eruption represented the Brunsting-Perry variant of cicatricial pemphigoid. Here, we illustrated that a neutrophil-rich form of cicatricial pemphigoid can masquerade as a neutrophil-mediated scarring alopecia. In evaluating a specimen suspected to be a neutrophil-mediated scarring alopecia, one should be alert to the presence of subepidermal and perifollicular clefting, and consider cicatricial pemphigoid.
Subject(s)
Alopecia/pathology , Neutrophils/pathology , Pemphigoid, Benign Mucous Membrane/pathology , Aged , Humans , MaleABSTRACT
ABSTRACT: The seminal case report of plexiform melanocytic schwannoma, published a decade ago, indicated that this is a rare variant of schwannoma demonstrating immunohistochemical expression of melanocytic markers, electron microscopic evidence of melanosome formation, and genetic features of a benign schwannoma. We report herein, a second example of this entity. Of added interest, our case showed pseudoglandular features, as previously recorded in other variants of schwannoma. A 66-year-old man presented with a cutaneous papule on the abdomen. Histopathologically, a vertically oriented, exoendophytic, folliculocentric, dermal tumor with a plexiform architecture was observed. This was composed of nodules and diverging fascicles of bland spindle-shaped cells. Notable interstitial mucin deposition conveyed a pseudoglandular appearance to the lesion. The spindled cells co-expressed S100, SOX10, and HMB45. A minority of cells expressed Melan-A and MiTF. EMA and claudin-1 stained capsular and perifascicular perineurial cells. Melanin was absent. Plexiform melanocytic schwannoma represents one of several nerve sheath tumors that peculiarly display evidence of melanocytic differentiation. These include melanocytoneuroma, pigmented neurofibroma (or melanocytic neurofibroma), and malignant melanotic schwannian tumor. Of importance, these proliferations can be mistaken for melanocytic tumors, including melanoma. In expanding the literature on this topic, we discuss steps required to distinguish plexiform melanocytic schwannoma from melanoma and other nerve sheath tumors with melanocytic differentiation. The possible pathogenesis of these unusual neoplasms is also addressed.
Subject(s)
Melanoma , Nerve Sheath Neoplasms , Neurilemmoma , Neurofibroma , Precancerous Conditions , Male , Humans , Aged , Neurilemmoma/pathology , Melanoma/pathology , Nerve Sheath Neoplasms/pathology , Melanocytes/pathologyABSTRACT
OBJECTIVES: To characterize the skin and mucosal findings of NEMO syndrome. METHODS: Retrospective review of clinical characteristics from a cohort of two families with mutations in IKBKG (the NEMO-encoding gene). A literature review identified 86 studies describing 192 patients with IKBKG mutations whose data were also included. SETTING: Single center with literature review. PARTICIPANTS: Patients with mutations in IKBKG from our center and reported in the literature. MAIN OUTCOMES AND MEASURES: Skin and mucosal characteristics of patients with NEMO syndrome. RESULTS: In addition to ectodermal dysplasia and recurrent infections, male patients had findings of ichthyosis, palmoplantar keratoderma, and inflammatory skin diseases. Both male and female patients had mucocutaneous ulcers and slow-to-heal chronic wounds. In combination with patients from the literature, 59% (85/144) of males had ectodermal dysplasia with anhidrosis (EDA) features, and 8% and 10% (12/144; 6/63) of males and females had dental findings, respectively. 4% (6/144) of males and 32% (20/63) of females had mucocutaneous ulcers. Ichthyosis/xerosis was present in 15% of males (21/144) but only 2% (1/63) females. Similarly, 13% (18/144) of male patients presented with dermatitis while this was reported in only 2% (1/63) of females. CONCLUSIONS: Our results both confirm and expand upon the known spectrum of mucocutaneous findings in NEMO syndrome. Further genetic studies are needed to correlate specific mutations to clinical and morphologic subtypes.
Subject(s)
Ectodermal Dysplasia , Immunologic Deficiency Syndromes , Incontinentia Pigmenti , Ectodermal Dysplasia/genetics , Female , Humans , I-kappa B Kinase/genetics , Male , Mutation , Retrospective StudiesABSTRACT
A subset of Spitz tumors harbor fusions of NTRK3 with ETV6, MYO5A, and MYH9. We evaluated a series of 22 melanocytic tumors in which an NTRK3 fusion was identified as part of the diagnostic workup. Tumors in which NTRK3 was fused to ETV6 occurred in younger patients were predominantly composed of epithelioid melanocytes and were classified by their histopathologic features as Spitz tumors. In contrast, those in which NTRK3 was fused to MYO5A were predominantly composed of spindled melanocytes arrayed in fascicles with neuroid features such as pseudo-Verocay bodies. To further investigate the effects of the fusion kinases ETV6-NTRK3 and MYO5A-NTRK3 in melanocytes, we expressed them in immortalized melanocytes and determined their subcellular localization by immunofluorescence. ETV6-NTRK3 was localized to the nucleus and diffusely within the cytoplasm and caused melanocytes to adopt an epithelioid cytomorphology. In contrast, MYO5A-NTRK3, appeared excluded from the nucleus of melanocytes, was localized to dendrites, and resulted in a highly dendritic cytomorphology. Our findings indicate that ETV6-NTRK3 and MYO5A-NTRK3 have distinct subcellular localizations and effects on cellular morphology.
Subject(s)
Biomarkers, Tumor/genetics , Gene Fusion , Melanocytes/pathology , Myosin Heavy Chains/genetics , Myosin Type V/genetics , Nevus, Epithelioid and Spindle Cell/genetics , Oncogene Proteins, Fusion/genetics , Receptor, trkC/genetics , Skin Neoplasms/genetics , Adolescent , Adult , Aged , Cell Line , Cell Shape , Child , Child, Preschool , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Nevus, Epithelioid and Spindle Cell/enzymology , Nevus, Epithelioid and Spindle Cell/pathology , Phenotype , Skin Neoplasms/enzymology , Skin Neoplasms/pathology , Young AdultABSTRACT
BACKGROUND: BRCA1-associated protein (BAP1) is a tumor suppressor whose loss is associated with various malignancies. The primary cilium is an organelle involved in signal transduction and cell cycle progression. Primary cilia have been shown to be absent in melanoma but retained to some extent in melanocytic nevi, and the severity of dysplasia influences the degree of cilia loss. Additionally, studies have revealed roles for BAP1 in centrosome and mitotic spindle formation. Because the primary cilium is nucleated on the mother centriole, we examined the connection between the presence of primary cilia and the formation of centrosomes in BAP1-inactivated melanocytic tumors (BIMTs). METHODS: We evaluated the cilia and centrosomes in 11 BIMTs and five conventional melanocytic nevi using immunofluorescence staining of acetylated alpha-tubulin and gamma-tubulin. RESULTS: We found that, compared to nevi, BIMTs show loss of primary cilia and amplification of centrosomes. Occasional nevi also showed increased centrioles; however, these foci of amplification were more likely to be ciliated than those in BIMTs. CONCLUSIONS: Although centrosome amplification does not absolutely correlate with loss of primary cilia in melanocytic neoplasms, absence of BAP1 exacerbates the phenotype. Moreover, aberrant centrosome and cilia formation are likely critical in the pathogenesis of other BAP1-inactivated tumors.
Subject(s)
Centrosome/pathology , Cilia/pathology , Melanoma/pathology , Skin Neoplasms/pathology , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Adolescent , Adult , Aged , Female , Gene Silencing , Humans , Male , Melanoma/genetics , Middle Aged , Nevus, Pigmented/genetics , Nevus, Pigmented/pathology , Skin Neoplasms/genetics , Young AdultABSTRACT
ABSTRACT: Pseudocarcinomatous desmoplastic trichoepithelioma (PDTE) features verrucous squamous epidermal hyperplasia with a jagged undersurface overlying cords of follicular germinative cells in a fibrotic stroma. To date, only 5 cases have been reported. We identified 7 new PDTEs from 2 institutions and reviewed their clinical manifestations and immunohistochemical profile. The median age was 14 years (range 8-34 years). New findings included vacuolization of the basal layer of the pseudocarcinomatous surface epithelium, and the frequent presence of singly distributed sebocytes within the cords of basaloid cells. The immunohistochemical profile resembles desmoplastic trichoepithelioma, with expression of TDAG51, CK15, and Ber-Ep4. Colonizing CK20+ Merkel cells were present in all cases. PDTE needs to be differentiated from malignant neoplasms such as squamous cell carcinoma, morphoeic basal cell carcinoma, and microcystic adnexal carcinoma. Recognizing the features of this sclerosing folliculosebaceous neoplasm facilitates accurate diagnosis and avoids overtreatment.
Subject(s)
Hair Follicle/pathology , Sebaceous Gland Neoplasms/pathology , Adolescent , Adult , Biomarkers, Tumor/metabolism , Child , Diagnosis, Differential , Epithelium/pathology , Female , Humans , Hyperplasia/pathology , Keratin-15/metabolism , Male , Merkel Cells/pathology , Sebaceous Gland Neoplasms/diagnosis , Sebaceous Gland Neoplasms/metabolism , Transcription Factors/metabolism , Young AdultABSTRACT
DOCK8 immunodeficiency syndrome (DIDS) represents a rare primary immunodeficiency associated with cutaneous viral infections, allergy, and increased risk of malignancy. We report a case of folliculotropic mycosis fungoides with spontaneous resolution occurring in a patient with DIDS.
Subject(s)
Immunologic Deficiency Syndromes , Mycosis Fungoides , Skin Neoplasms , Guanine Nucleotide Exchange Factors , Humans , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/diagnosis , Mycosis Fungoides/complications , Mycosis Fungoides/diagnosis , Skin Neoplasms/complications , Skin Neoplasms/diagnosisABSTRACT
Melanomas that have histopathologic features that overlap with those of Spitz nevus are referred to as spitzoid melanomas. However, the diagnostic concept is used inconsistently and genomic analyses suggest it is a heterogeneous category. Spitz tumors, the spectrum of melanocytic neoplasms extending from Spitz nevi to their malignant counterpart Spitz melanoma, are defined in the 2018 WHO classification of skin tumors by the presence of specific genetic alterations, such as kinase fusions or HRAS mutations. It is unclear what fraction of "spitzoid melanomas" defined solely by their histopathologic features belong to the category of Spitz melanoma or to other melanoma subtypes. We assembled a cohort of 25 spitzoid melanomas diagnosed at a single institution over an 8-year period and performed high-coverage DNA sequencing of 480 cancer related genes. Transcriptome wide RNA sequencing was performed for select cases. Only nine cases (36%) had genetic alterations characteristic of Spitz melanoma, including HRAS mutation or fusion involving BRAF, ALK, NTRK1, or MAP3K8. The remaining cases were divided into those with an MAPK activating mutation and those without an MAPK activating mutation. Both Spitz melanoma and spitzoid melanomas in which an MAPK-activating mutation could not be identified tended to occur in younger patients on skin with little solar elastosis, infrequently harbored TERT promoter mutations, and had a lower burden of pathogenic mutations than spitzoid melanomas with non-Spitz MAPK-activating mutations. The MAPK-activating mutations identified affected non-V600 residues of BRAF as well as NRAS, MAP2K1/2, NF1, and KIT, while BRAF V600 mutations, the most common mutations in melanomas of the WHO low-CSD category, were entirely absent. While the "spitzoid melanomas" comprising our cohort were enriched for bona fide Spitz melanomas, the majority of melanomas fell outside of the genetically defined category of Spitz melanomas, indicating that histomorphology is an unreliable predictor of Spitz lineage.
Subject(s)
Melanoma/pathology , Nevus, Epithelioid and Spindle Cell/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Child , Child, Preschool , DNA Mutational Analysis , Female , Humans , Male , Melanoma/genetics , Melanoma/metabolism , Middle Aged , Mutation , Nevus, Epithelioid and Spindle Cell/genetics , Nevus, Epithelioid and Spindle Cell/metabolism , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Skin/metabolism , Skin/pathology , Skin Neoplasms/genetics , Skin Neoplasms/metabolism , Young AdultABSTRACT
We report a series of 33 skin tumors harboring a gene fusion of the MAP3K8 gene, which encodes a serine/threonine kinase. The MAP3K8 fusions were identified by RNA sequencing in 28 cases and by break-apart FISH in five cases. Cases in which fusion genes were fully characterized demonstrated a fusion of the 5' part of MAP3K8 comprising exons 1-8 in frame to one of several partner genes at the 3' end. The fusion genes invariably encoded the intact kinase domain of MAP3K8, but not the inhibitory domain at the C-terminus. In 13 (46%) of the sequenced cases, the 3' fusion partner was SVIL. Other recurrent 3' partners were DIP2C and UBL3, with additional fusion partners that occurred only in a single tumor. Clinically, the lesions appeared mainly in young adults (2-59 years of age; median = 18), most commonly involving the lower limbs (55%). Five cases were diagnosed as Spitz nevus, 13 as atypical Spitz tumor, and 15 as malignant Spitz tumor. Atypical and malignant cases more commonly occurred in younger patients. Atypical Spitz tumors and malignant Spitz tumors cases tended to show epidermal ulceration (32%), a dermal component with giant multinucleated cells (32%), and clusters of pigmented cells in the dermis (32%). Moreover, in atypical and malignant cases, a frequent inactivation of CDKN2A (21/26; 77%) was identified either by p16 immunohistochemistry, FISH, or comparative genomic hybridization. Gene expression analysis revealed that MAP3K8 expression levels were significantly elevated compared to a control group of 57 Spitz lesions harboring other known kinase fusions. Clinical follow-up revealed regional nodal involvement in two of six cases, in which sentinel lymph node biopsy was performed but no distant metastatic disease after a median follow-up time of 6 months.
Subject(s)
MAP Kinase Kinase Kinases/genetics , Nevus, Epithelioid and Spindle Cell/genetics , Nevus, Epithelioid and Spindle Cell/pathology , Proto-Oncogene Proteins/genetics , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Oncogene Proteins, Fusion , Young AdultABSTRACT
Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.
Subject(s)
Cilia/pathology , Melanoma/pathology , Nevus, Pigmented/pathology , Skin Neoplasms/pathology , Adult , Aged , Female , Humans , Male , Melanoma/diagnosis , Middle Aged , Skin Neoplasms/diagnosis , Melanoma, Cutaneous MalignantABSTRACT
BACKGROUND/OBJECTIVES: A recent marked increase in pediatric and adult patients presenting with purpuric acral lesions concerning for ischemia, thrombosis and necrosis has been observed in COVID-19 prevalent regions worldwide. The clinical and histopathological features and relationship to COVID-19 have not been well described. The objective of this case series is to describe the clinical features and determine the histopathologic findings and clinical implications of the clusters of acral perniosis cases identified in pediatric patients. METHODS: We describe six otherwise healthy adolescents-three siblings per family from two unrelated families-presented within a 48-hour period in April, 2020, with acral perniosis-like lesions in the context of over 30 similar patients who were evaluated within the same week. RESULTS: Affected patients had mild symptoms of viral upper respiratory infection (URI) or contact with symptomatic persons 1-2 weeks preceding the rash. They all presented with red to violaceous macules and dusky, purpuric plaques scattered on the mid and distal aspects of the toes. Skin biopsies performed on each of the six patients demonstrated near identical histopathologic findings to those of idiopathic perniosis, with a lymphocytic inflammatory infiltrate without evidence of thromboembolism or immune complex vasculitis. While SARS-CoV-2 polymerase chain reaction was negative, testing was performed 1-2 weeks after URI symptoms or sick contact exposure. CONCLUSION: We offer a clinical approach to evaluation of patients with this presentation and discuss the possibility that these skin findings represent a convalescent-phase cutaneous reaction to SARS-CoV-2 infection.
Subject(s)
Betacoronavirus , Chilblains/pathology , Chilblains/virology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Adolescent , COVID-19 , Chilblains/therapy , Child , Cluster Analysis , Cohort Studies , Coronavirus Infections/therapy , Female , Humans , Male , Pandemics , Pneumonia, Viral/therapy , SARS-CoV-2 , Siblings , Symptom AssessmentABSTRACT
BACKGROUND: Inpatient dermatology consultations for treatment-refractory or atypical cellulitis are common. In critically ill patients, differentiating cellulitis from its mimickers can be challenging. OBJECTIVE: We describe acute inflammatory edema, a likely underrecognized variant of pseudocellulitis. METHODS: We reviewed the charts of 15 patients with this diagnosis, seen by the inpatient dermatology consultation service at the University of California at San Francisco between 2009 and 2017. RESULTS: The cohort consisted of 9 women and 6 men with an age range of 52-73 years. Acute inflammatory edema presents as bilateral, erythematous, and edematous plaques, most commonly involving the thighs and lower abdomen, sparing areas of increased pressure on the skin. There is a predilection for patients with high body mass index and those with clinical or quantitative findings of fluid overload. CONCLUSION: We propose a 3-part pathogenesis of acute inflammatory edema: 1) acute-onset volume overload 2) in patients with impaired lymphatic return 3) leads to dermal edema, microtears in connective tissue, and an influx of inflammation.
Subject(s)
Cellulitis/diagnosis , Dermatitis/diagnosis , Dermatitis/etiology , Edema/diagnosis , Edema/etiology , Abdomen , Acute Disease , Aged , Body Water , Critical Illness , Diagnosis, Differential , Female , Humans , Male , Middle Aged , ThighSubject(s)
Carcinoma in Situ , Eccrine Porocarcinoma , Keratosis, Seborrheic , Poroma , Skin Neoplasms , Sweat Gland Neoplasms , Humans , Keratosis, Seborrheic/diagnosis , Poroma/diagnosis , Immunohistochemistry , Diagnosis, Differential , Skin Neoplasms/diagnosis , Eccrine Porocarcinoma/diagnosis , Carcinoma in Situ/diagnosis , Sweat Gland Neoplasms/diagnosis , GATA3 Transcription FactorABSTRACT
Heavily pigmented melanocytic neoplasms are genotypically and phenotypically diverse. Recently, a subset of this histopathologic spectrum was shown to harbor recurrent genetic alterations in the gene-encoding protein kinase A regulatory subunit-α (PRKAR1A). To date, no histopathologic descriptions of melanomas arising from this pathway have been described. We present a case of a darkly pigmented papule arising on the posterior neck of a 28-year-old man. Microscopically, the heavily pigmented compound melanocytic proliferation was centered in the dermis with permeation into the superficial subcutis. Tumor cells were arranged in large confluent nests and fascicles and lacked maturation with descent. The epithelioid melanocytes were characterized by enlarged vesicular nuclei with prominent nucleoli, nuclear pleomorphism, and plentiful gray-brown granular cytoplasm. Mitotic figures were readily identified. By immunohistochemistry, melanocytes were positive for mutant BRAF V600E and showed loss of Prkar1α and p16 expression. A multiplex MART-1/tyrosinase/phosophohistone-H3 immunostain demonstrated an increased mitotic index in melanocytes. The combination of highly atypical cytomorphology and architecture, increased mitoses, and p16 expression loss compelled the diagnosis of melanoma. Overall, we present the first clinicopathologic description of a PRKAR1A-inactivated melanoma to highlight morphological features and discuss mimics that may enter the differential diagnosis.
Subject(s)
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/biosynthesis , Melanoma/pathology , Skin Neoplasms/pathology , Adult , Biomarkers, Tumor/analysis , Humans , MaleABSTRACT
The distinction between subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus (LE) panniculitis is remarkably challenging. Rimming by lymphocytes with an elevated Ki-67 cell proliferation index has been forwarded as a potential diagnostic finding in biopsies of SPTCL but has not been rigorously compared with biopsies from patients with LE panniculitis. Nineteen and 17 examples of SPTCL and LE panniculitis, respectively, were evaluated for periadipocytic rimming by lymphocytes expressing Ki-67, CD8, and ßF1 and for attributes associated with LE, including clusters of CD123-positive cells. The identification of periadiopocytic rimming using Ki-67, CD8, and ßF1 held sensitivity of 79%, 100%, and 89.5% and specificity of 100%, 52.9%, and 88.2%, respectively (P < 0.01). CD123-positive cells were in both disorders. LE-like histopathology was commonly encountered in SPTCL. In conclusion, an elevated Ki-67 cell proliferation index with rimming is useful for distinguishing SPTCL from LE panniculitis. Notably, many features of LE panniculitis can also be encountered in SPTCL.