Subject(s)
Mycosis Fungoides , Skin Neoplasms , Humans , T-Lymphocytes , Prognosis , Mycosis Fungoides/diagnosis , Skin Neoplasms/diagnosis , Clone CellsABSTRACT
Importance: There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of well-documented large case series published to date. Objective: To generate consensus knowledge by a joint multi-institutional review of SPTCL and related conditions. Design, Setting, and Participants: This retrospective clinical and pathological review included cases initially diagnosed as SPTCL at 6 large US academic centers. All cases were reviewed by a group of pathologists, dermatologists, and oncologists with expertise in cutaneous lymphomas. Through a process of group consensus applying defined clinical and pathological diagnostic criteria, the cohort was classified as (1) SPTCL or (2) adipotropic lymphoproliferative disorder (ALPD) for similar cases with incomplete histopathological criteria for SPTCL designation. Exposures: Cases of SPTCL diagnosed between 1998 and 2018. Main Outcomes and Measures: The main outcome was disease presentation and evolution, including response to therapy, disease progression, and development of hemophagocytic lymphohistiocytosis. Results: The cohort of 95 patients (median [range] age, 38 [2-81] years; female-to-male ratio, 2.7) included 75 cases of SPTCL and 20 cases of ALPD. The clinical presentation was similar for both groups with multiple (61 of 72 [85%]) or single (11 of 72 [15%]) tender nodules mostly involving extremities, occasionally resulting in lipoatrophy. Hemophagocytic lymphohistiocytosis (HLH) was only observed in SPTCL cases. With a mean follow-up of 56 months, 60 of 90 patients (67%) achieved complete remission with a median (range) of 3 (1-7) cumulative therapies. Relapse was common. None of the patients died of disease progression or HLH. Two patients with ALPD eventually progressed to SPTCL without associated systemic symptoms or HLH. Conclusions and Relevance: In this case series of patients initially diagnosed as having SPTCL, results showed no evidence of systemic tumoral progression beyond the adipose tissue. The SPTCL experience in this study confirmed an indolent course and favorable response to a variety of treatments ranging from immune modulation to chemotherapy followed by hematopoietic stem cell transplantation. Morbidity was primarily associated with HLH.
Subject(s)
Lymphohistiocytosis, Hemophagocytic , Lymphoma, T-Cell , Panniculitis , Humans , Male , Female , Adult , Retrospective Studies , Neoplasm Recurrence, Local , Panniculitis/diagnosis , Panniculitis/therapy , Panniculitis/pathology , Lymphoma, T-Cell/complications , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/therapy , Disease ProgressionABSTRACT
CD70 is a member of the tumor necrosis factor receptor superfamily. Emerging data indicate that CD70 may be a suitable target for various malignancies. We investigated the expression of CD70 in cutaneous and systemic T-cell lymphomas and conducted preclinical studies of SGN-CD70A, a CD70-directed antibody-drug conjugate (ADC), using patient-derived xenograft cutaneous T-cell lymphoma (CTCL PDX) models. CD70 expression was examined by immunohistochemical (IHC) stains in 49 diagnostic specimens of T-cell lymphomas. The activities of SGN-CD70A in growth inhibition and apoptosis induction were examined in CTCL cell lines and primary CTCL tumor cells. Using previously established CTCL PDXs, we conducted a dose-finding trial followed by a phase 2-like trial to evaluate the optimal dosing and the efficacy of SGN-CD70A in tumor-bearing PDX animals. The therapeutic efficacy of SGN-CD70A was measured by tumor-associated cell-free DNA (cfDNA) and survival of treated PDXs. We found that CD70 is highly expressed in T-cell lymphomas, especially in CTCL. SGN-CD70A inhibited cell growth and induced apoptosis in CD70-expressing CTCL cell lines and primary tumors cells. Additionally, SGN-CD70A at 100 µg/kg and 300 µg/kg prolonged the survival of PDXs in a dose-dependent manner. Finally, treatment with 3 doses of SGN-CD70A at 300 µg/kg was superior to a single-dose treatment in survival prolongation (median survival: 111 days vs 39 days; P = .017). Most importantly, multiple dosing of SGN-CD70A induced complete eradication of established tumors in PDXs measured by cfDNA. Our results demonstrated marked antitumor activity of SGN-CD70A in CTCL PDXs, providing compelling support for its clinical investigation.
Subject(s)
Immunoconjugates , Lymphoma, T-Cell, Cutaneous , Skin Neoplasms , Animals , CD27 Ligand/metabolism , Heterografts , Humans , Immunoconjugates/pharmacology , Immunoconjugates/therapeutic use , Lymphoma, T-Cell, Cutaneous/drug therapy , Skin Neoplasms/drug therapyABSTRACT
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
Syphilis has many atypical morphologies which can present a diagnostic challenge, especially in patients with HIV/AIDS who may have multiple concurrent conditions. We describe a 41-year-old man with recently diagnosed HIV who was admitted for acute right vision loss and a diffuse rash with involvement of the palms and soles. He received diagnoses of secondary syphilis and Kaposi sarcoma in the setting of AIDS. Examination revealed an unusual dark brown-to-purple umbilicated papule with a necrotic center on the abdomen, raising a diagnostic dilemma. Skin biopsy showed secondary syphilis, despite the concurrent diagnosis of Kaposi sarcoma. The patient was treated with antibiotic and antiretroviral therapy and symptoms resolved. This case aims to share the clinical reasoning behind diagnosing a patient with HIV/AIDS with multiple concurrent conditions and to raise awareness of the many atypical cutaneous manifestations of secondary syphilis.
Subject(s)
Skin Diseases, Bacterial/diagnosis , Syphilis/diagnosis , Abdomen , Acquired Immunodeficiency Syndrome/complications , Adult , Humans , Male , Skin Diseases, Bacterial/complications , Syphilis/complicationsABSTRACT
Distinguishing cellular blue nevi (CBNs) and atypical CBNs from blue nevus-like melanoma (BNLM) can be diagnostically challenging. Immunohistochemistry may inform the diagnosis in a subset of cases but is not always diagnostic. Further, ancillary molecular testing is expensive and often requires significant tissue to complete. Primary cilia are cell-surface organelles with roles in signal transduction pathways and have been shown to be preserved in conventional melanocytic nevi but lost in melanoma. Immunofluorescence staining of primary cilia can be performed using a single standard-thickness formalin-fixed paraffin-embedded tissue section and has a turnaround time similar to immunohistochemistry. The percentage of tumoral melanocytes retaining a primary cilium is quantified and reported as the ciliation index. In the current study, we explored the utility of the ciliation index in a series of 31 blue nevus-like lesions, including CBNs (12), atypical CBNs (15), and BNLM (4). The average ciliation index for the CBNs was 59±18%, with a median of 60 (range: 28 to 87). The average ciliation index for atypical CBNs was 59±23, with a median of 59 (range: 20 to 93). The average ciliation index for BNLM was 4±3, with a median of 3 (range: 1 to 8). There was no significant difference in ciliation index between the CBN and atypical CBN categories. There was a significant difference between CBN and BNLM and between atypical CBNs and BNLM (P<0.001 for each). Here, we show that ciliation index is a quantitative diagnostic tool useful in the setting of blue nevus-like neoplasms, with benefits including cost and time efficiency.
Subject(s)
Cilia/pathology , Melanoma/pathology , Nevus, Blue/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young AdultSubject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Drug Eruptions/diagnosis , Facial Dermatoses/diagnosis , Neutrophils/immunology , 2019-nCoV Vaccine mRNA-1273 , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , COVID-19/immunology , COVID-19/virology , Dermatologic Agents/administration & dosage , Diagnosis, Differential , Drug Eruptions/drug therapy , Drug Eruptions/immunology , Drug Eruptions/pathology , Drug Therapy, Combination , Facial Dermatoses/drug therapy , Facial Dermatoses/immunology , Facial Dermatoses/pathology , Humans , Male , Middle Aged , Rosacea/diagnosis , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Skin/immunology , Skin/pathology , Treatment OutcomeABSTRACT
BACKGROUND: Cutaneous involvement by classic Hodgkin lymphoma (CHL) is an extraordinarily rare phenomenon in the current era. To date, no single large case series of cutaneous involvement by Hodgkin lymphoma has ever been reported in the literature. METHODS: A comprehensive search for cases designated "skin" and "Hodgkin" was performed at different institutions between 1990 and 2020. Twenty-five cases were identified, and each case was independently reviewed by at least three board-certified dermatopathologists and/or hematopathologists. RESULTS: All cases represented examples of systemic CHL with secondary skin dissemination. A single lesion, usually a tumor, nodule or infiltrative plaque was observed in 56% of cases and multiple lesions were present in 28% of cases. Most patients (86%-12/14) had a diagnosis of stage IV disease at first diagnosis. The interval between the clinical (first) diagnosis of HL and the development of skin lesions ranged between 6 and 108 months (average 33.75 months). Comprehensive histopathologic evaluation of these cases (at the initial diagnosis) revealed a diagnosis of classic HL not otherwise specified (NOS) in 60% of cases (15/25), nodular sclerosis type in 24% (6/25), mixed cellularity in 12% (3/25), and lymphocyte depleted in 4% (1/25). CONCLUSIONS: We provide documentation of a large series of CHL with secondary skin involvement in association with CHL with additional clinical, morphologic, and immunophenotypic features.
Subject(s)
Hodgkin Disease/pathology , Skin Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Cutaneous T-cell lymphoma is a form of non-Hodgkin lymphoma that manifests initially in the skin and disseminates systemically as the disease progresses. Mycosis fungoides and Sézary syndrome are the most common subtypes of cutaneous T-cell lymphoma. Advanced mycosis fungoides and Sézary syndrome are life threatening with few treatment options. We searched for new agents by high-throughput screening of selected targeted compounds and identified high-value targets, including phosphatidylinositol 3-kinase (PI3K) and cyclin-dependent kinases. To validate these hits from the screen, we developed patient-derived xenograft mouse models that recapitulated the cardinal features of mycosis fungoides and Sézary syndrome and maintained histologic and molecular characteristics of their clinical counterparts. Importantly, we established a blood-based biomarker assay using tumor cell-free DNA to measure systemic tumor burden longitudinally in living mice during drug therapy. A PI3K inhibitor, BKM120, was tested in our patient-derived xenograft model leading to disease attenuation and prolonged survival. Isoform-specific small interfering RNA knockdowns and isoform-selective PI3K inhibitors identified PI3K-δ as required for tumor proliferation. Additional studies showed a synergistic combination of PI3K-α/δ inhibitors with histone deacetylase inhibitors. The strong preclinical efficacy of this potent combination against multiple patient-derived xenograft models makes it an excellent candidate for further clinical development.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Histone Deacetylase Inhibitors/pharmacology , Lymphoma, T-Cell, Cutaneous/drug therapy , Protein Kinase Inhibitors/pharmacology , Skin Neoplasms/drug therapy , Aminopyridines/pharmacology , Aminopyridines/therapeutic use , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Line, Tumor , Circulating Tumor DNA/blood , Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Drug Synergism , Female , Gene Knockdown Techniques , High-Throughput Screening Assays , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylases/metabolism , Humans , Lymphoma, T-Cell, Cutaneous/blood , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/pathology , Mice , Morpholines/pharmacology , Morpholines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Skin/pathology , Skin Neoplasms/blood , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Tumor Burden/drug effects , Xenograft Model Antitumor AssaysABSTRACT
Importance: A new cutaneous staging system for folliculotropic mycosis fungoides (FMF) has been purported to better estimate survival compared with the staging system for conventional mycosis fungoides. Objective: To analyze predictive variables associated with survival and evaluate the effectiveness of the newly proposed staging system for estimating overall survival and disease-specific survival (DSS) in a US cohort. Design, Setting, and Participants: This cohort study assessed 195 patients with FMF in the dermatopathology database of the University of California, San Francisco from January 1, 1990, to April 31, 2012, for eligibility. A total of 153 patients were excluded for the following reasons: (1) alternative diagnoses were favored ranging from benign dermatitides to other forms of cutaneous lymphoma; (2) technical problems with slides; and (3) lack of follow-up information. Data were analyzed from January 1, 2018, to August 31, 2020. Main Outcomes and Measures: Kaplan-Meier curves were used to estimate overall survival and DSS for the entire cohort. Possible predictive variables associated with survival were evaluated using Cox proportional hazards regression modeling. Each variable was examined separately, followed by a multiple-variable model. Kaplan-Meier curves were used to estimate overall survival and DSS by subdividing the cohort into early- and advanced-stage cutaneous disease. Results: Forty-two patients were included in the analysis (mean age at diagnosis, 55 [range, 8-89] years; 31 men [74%]). For the entire cohort, the estimated 5-year overall survival rate was 89% (95% CI, 79%-99%); 10-year rate, 78% (95% CI, 63%-92%); and 15-year rate, 58% (95% CI, 31%-85%). Estimated 5- and 10-year DSS rates were 89% (95% CI, 79%-99%); 15-year rate, 80% (95% CI, 61%-99%). For overall survival in the multiple-variable Cox proportional hazards regression model, only age was statistically significant (hazard ratio [HR] per 10-year age increase, 3.1; 95% CI, 1.4-7.2; P = .008), whereas for DSS, only cutaneous disease was statistically significant (HR, 11.4; 95% CI, 1.3-103.0; P = .03). When stage stratified, the 5-year estimated overall survival rate for early-stage disease was 96% (95% CI, 89%-103%); 10-year rate, 82% (95% CI, 65%-98%); and 15-year rate, 65% (95% CI, 33%-97%). For advanced-stage disease, the estimated 5- and 10-year overall survival rates were 70% (95% CI, 41%-98%); the 15-year rate, 53% (95% CI, 16%-89%). For early-stage cutaneous disease, the estimated 5-, 10- and 15-year DSS rates were all 96% (95% CI, 89%-103%). For advanced-stage cutaneous disease, the estimated 5- and 10-year DSS rates were 70% (95% CI, 41%-98%); the 15-year rate, 53% (95% CI, 16%-89%). Conclusions and Relevance: Cox proportional hazards regression modeling demonstrated cutaneous stage to be the only statistically significant predictive variable associated with DSS. Subdividing FMF into early and advanced cutaneous stages was associated with effective estimation of survival in this cohort. Thus, findings suggest that FMF is a heterogeneous disease with early and advanced cutaneous stages; that the new staging system is effective in estimating survival in a US cohort; and that the poor prognosis initially associated with FMF only applies to the advanced cutaneous stage.
Subject(s)
Mycosis Fungoides/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mycosis Fungoides/diagnosis , Neoplasm Staging , Prognosis , Skin Neoplasms/diagnosis , Survival Rate , Time Factors , United States , 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
PURPOSE: The histone deacetylase (HDAC) inhibitor romidepsin and the anthracycline liposomal doxorubicin (LD) have modest single-agent activity in cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). We investigated the safety and efficacy of the combination of these two agents in CTCL and PTCL. PATIENTS AND METHODS: Using CTCL cell lines and primary CTCL tumor cells, we demonstrated synergistic antitumor activity with romidepsin plus doxorubicin. We then conducted a phase I dose-escalation study of the romidepsin/LD combination in relapsed/refractory CTCL and PTCL. The primary objective was to determine the MTD of romidepsin in combination with LD at 20 mg/m2 i.v., once every 28 days. RESULTS: Eleven patients with CTCL and 12 patients with PTCL were treated. The MTD of romidepsin was determined to be 12 mg/m2. Grade 3/4 hematologic toxicities included thrombocytopenia (17%), anemia (13%), and neutropenia (9%). The most frequent treatment-related nonhematologic adverse events were fatigue (48%), nausea (48%), vomiting (35%), and anorexia (30%). Among 21 evaluable patients, the overall response rate was 70% [1 complete response (CR), 6 partial responses (PR)] in CTCL and 27% (3 CR, 0 PR) in PTCL. Of the patients with CTCL, 8 of 10 had skin response, including 6 patients (60%) achieving skin involvement less than 10% of their body surface area at time of best response. CONCLUSIONS: Romidepsin plus LD demonstrated an acceptable safety profile and promising clinical efficacy with deep skin responses in relapsed/refractory CTCL. Thus, this combination could be considered as a bridge to skin-directed treatment or allogeneic hematopoietic cell transplantation in patients with aggressive CTCL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, T-Cell, Cutaneous/drug therapy , Lymphoma, T-Cell, Peripheral/drug therapy , Lymphoma, T-Cell/drug therapy , Neoplasm Recurrence, Local/drug therapy , Skin Neoplasms/drug therapy , Aged , Aged, 80 and over , Apoptosis , Cell Line, Tumor , Depsipeptides/administration & dosage , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/analogs & derivatives , Female , Humans , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell, Cutaneous/pathology , Lymphoma, T-Cell, Peripheral/pathology , Male , Middle Aged , Nausea/chemically induced , Neoplasm Recurrence, Local/pathology , Neutropenia/chemically induced , Patient Safety , Polyethylene Glycols/administration & dosage , Prospective Studies , Skin Neoplasms/pathology , Thrombocytopenia/chemically induced , Treatment Outcome , Vomiting/chemically inducedABSTRACT
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 , ThighABSTRACT
OBJECTIVES: We observed keratoses with "clonal" nests present as numerous tiny collections, in which cells in "pagetoid" array are found, a configuration we termed microclonal seborrheic keratosis (MSK). To better distinguish MSK from pagetoid Bowen disease (PBD), we investigated use of immunohistochemical staining. METHODS: Biopsy specimens of 26 MSKs, 17 PBDs, and 11 borderline cases were reviewed for histopathology and stained with p53, Ki-67, and p16. RESULTS: High expression of Ki-67 and p16 was observed in 12 (80%) of 15 PBDs and in one (4%) of 23 MSKs. Low expression of p16 and high expression of Ki-67 were observed in 16 (70%) of 23 MSKs and in two (13%) of 15 PBDs. Expression of p16 was elevated in 12 (80%) of 15 PBDs and in three (13%) of 23 MSKs (P < .0001). CONCLUSIONS: We describe a "microclonal" variant of seborrheic keratosis with morphology sometimes challenging to distinguish from PBD. High expression of p16 and Ki-67 or p16 alone favors the diagnosis of PBD over MSK.
Subject(s)
Bowen's Disease/diagnosis , Cyclin-Dependent Kinase Inhibitor p16/analysis , Keratosis, Seborrheic/diagnosis , Ki-67 Antigen/analysis , Skin Neoplasms/diagnosis , Bowen's Disease/chemistry , Diagnosis, Differential , Humans , Immunohistochemistry , Keratosis, Seborrheic/metabolismABSTRACT
We elucidated genomic and transcriptomic changes that accompany the evolution of melanoma from pre-malignant lesions by sequencing DNA and RNA from primary melanomas and their adjacent precursors, as well as matched primary tumors and regional metastases. In total, we analyzed 230 histopathologically distinct areas of melanocytic neoplasia from 82 patients. Somatic alterations sequentially induced mitogen-activated protein kinase (MAPK) pathway activation, upregulation of telomerase, modulation of the chromatin landscape, G1/S checkpoint override, ramp-up of MAPK signaling, disruption of the p53 pathway, and activation of the PI3K pathway; no mutations were specifically associated with metastatic progression, as these pathways were perturbed during the evolution of primary melanomas. UV radiation-induced point mutations steadily increased until melanoma invasion, at which point copy-number alterations also became prevalent.