ABSTRACT
We present a 3-year-old boy with Langerhans cell histiocytosis who developed granulomatous dermatitis while taking vemurafenib. Vemurafenib currently has Food and Drug Administration approval for the treatment of BRAF V600E+ metastatic melanoma in adults, but recent discoveries of BRAF V600E in more than half of tested Langerhans cell histiocytosis lesions have prompted clinical trials of vemurafenib therapy for children with refractory, multisystem Langerhans cell histiocytosis. This report contributes to the knowledge of its potential side effects when used in children.
Subject(s)
Antineoplastic Agents/adverse effects , Drug Eruptions/diagnosis , Histiocytosis, Langerhans-Cell/drug therapy , Indoles/adverse effects , Sulfonamides/adverse effects , Child, Preschool , Drug Eruptions/drug therapy , Drug Eruptions/etiology , Glucocorticoids/therapeutic use , Granuloma/etiology , Humans , Male , Skin/pathology , Triamcinolone/therapeutic use , VemurafenibABSTRACT
BACKGROUND: The GATA family of transcription factors is an essential regulator of cellular proliferation and differentiation. In the skin, GATA-3 is critical for epidermal stratification and maintenance of barrier function. A role for GATA-3 in the development of human cutaneous squamous cell carcinoma (SCC) is not known. Here, we investigated GATA-3 immunohistochemical staining in premalignant and invasive cutaneous SCC from sun-exposed and sun-protected skin. METHODS: GATA-3 immunohistochemistry was performed on actinic keratoses (AK) (n = 19), in situ squamous cell carcinomas with actinic [SCCIS (A)] (n = 9) or bowenoid features [SCCIS (B)] (n = 17), well-, moderately and poorly differentiated SCC (n = 36), Bowenoid papulosis of the perineum (n = 15) and penile SCC (pSCC) (n = 10). RESULTS: We found that GATA-3 immunohistochemical staining is progressively lost in sun-exposed skin as neoplasia progresses from pre-cancerous AK to SCCIS (A), and ultimately, to SCC, which shows near absent GATA-3 staining. This reduction in GATA-3 staining is independent of histological grade in SCC. Only slight down-regulation of GATA-3 was seen in all cases of SCCIS (B) and Bowenoid papulosis, while near absent GATA-3 expression was seen in pSCC. CONCLUSION: We propose that decreased GATA-3 immunohistochemical staining is associated with cutaneous SCC progression on both sun-exposed and sun-protected sites.
Subject(s)
Carcinoma, Squamous Cell , GATA3 Transcription Factor/metabolism , Neoplasm Proteins/metabolism , Aged , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Female , Humans , Immunohistochemistry , Male , Skin Neoplasms/metabolism , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Mantle cell lymphoma (MCL) is associated with the worst prognosis among low-grade B-cell lymphomas. While cutaneous involvement by nodal or systemic MCL is uncommon, its differentiation from primary cutaneous B-cell lymphoma (CBCL) or cutaneous involvement by other extra-cutaneous BCL is challenging as neither histomorphology nor immunophenotype can be absolutely specific. We analyzed the diagnostic utility of SOX11 immunohistochemistry in differentiating secondary cutaneous MCL from other low-grade CBCL. METHODS: Immunohistochemical staining with anti-SOX11 antibody was performed on 8 cases of secondary cutaneous MCL, 16 secondary cutaneous CLL, 20 primary cutaneous MZL, 12 cutaneous FCL (6 primary, 6 secondary), 7 primary cutaneous DLBCL, leg type, 5 systemic DLBCL and 3 B-ALL. SOX11 and cyclin D1 staining were compared in secondary cutaneous MCL. RESULTS: Nuclear SOX11 staining was seen in seven of eight cases (88%) of secondary cutaneous MCL, including a case with minimal cyclin D1 expression. All other CBCL lacked detectable nuclear SOX11 expression. The sensitivity and specificity for SOX11 in MCL were 87.5 and 100%, respectively. Both the sensitivity and specificity for combined SOX11 and cyclin D1 immunohistochemistry were 100%. CONCLUSION: SOX11 immunohistochemistry could be a useful adjunct in distinguishing secondary cutaneous MCL from other CBCL.
Subject(s)
Cell Nucleus , Lymphoma, B-Cell , Lymphoma, Mantle-Cell , Neoplasm Proteins/metabolism , SOXC Transcription Factors/metabolism , Skin Neoplasms , Adolescent , Adult , Aged , Aged, 80 and over , Cell Nucleus/metabolism , Cell Nucleus/pathology , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Lymphoma, B-Cell/metabolism , Lymphoma, B-Cell/pathology , Lymphoma, Mantle-Cell/metabolism , Lymphoma, Mantle-Cell/pathology , Male , Middle Aged , Skin Neoplasms/metabolism , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Mycosis fungoides (MF) is a neoplasm of skin-homing CD4(+) helper T (TH) lymphocytes with dysregulation of TH1 and TH2 immunity. Diagnosis of MF is challenging, as there is significant morphologic overlap with other dermatologic entities. OBJECTIVE: We investigated diagnostic utility of TH1- and TH2-specific markers, T-bet, and GATA-3, respectively, in MF and its reactive and neoplastic mimics. METHODS: Immunohistochemical staining for CD3/T-bet and CD3/GATA-3 was performed on inflammatory dermatoses (n = 56), MF (n = 37), Sezary syndrome (SS; n = 8), and cutaneous anaplastic large cell lymphoma (C-ALCL; n = 14). RESULTS: Inflammatory dermatoses showed epidermal T cells predominantly expressing GATA-3, except psoriasis, which exhibited a mixed GATA-3/T-bet staining. In contrast, neoplastic T cells in patch stage MF showed markedly increased T-bet positivity with minimal GATA-3 expression. Plaque stage MF had a mixed T-bet/GATA-3 phenotype, whereas tumor stage MF and SS exhibited diffuse GATA-3 expression. C-ALCL lacked significant staining for both markers. LIMITATIONS: Sample size was relatively small. CONCLUSIONS: A predominance of T-bet(+) T cells in the epidermis support patch stage MF over dermatitis. A predominance of GATA-3(+) T cells in the dermis support CD30(+) MF with large cell transformation over C-ALCL. These stains do not allow distinction between dermatitis and cutaneous infiltrates of SS.
Subject(s)
Dermatitis/immunology , GATA3 Transcription Factor/biosynthesis , Lymphoma, T-Cell, Cutaneous/immunology , Skin Neoplasms/immunology , T-Box Domain Proteins/biosynthesis , T-Lymphocytes, Helper-Inducer/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Dermatitis/diagnosis , Female , Humans , Lymphoma, T-Cell, Cutaneous/diagnosis , Male , Middle Aged , Skin Neoplasms/diagnosis , Young AdultABSTRACT
Inflammatory dermatoses encompass a variety of histologic patterns that affect different portions of the skin. In spongiotic, psoriasiform, lichenoid, pityriasiform, and blistering disorders, there are predominately epidermal and junctional activities with variable superficial dermal inflammation. Hypersensitivity reactions can show either epidermal or mostly dermal changes depending on whether the exposure of the exogenous allergen occurs through an external or internal route, respectively. Exceptions include erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis, where the etiology is often due to infection or ingested medications, but the histologic features are almost exclusively confined to the epidermis and dermoepidermal junction. Autoimmune disorders are unique in that lesions typically incorporate a mixture of epidermal and dermal inflammatory patterns with periadnexal inflammation, while the vast majority of vasculitis/vasculopathy and alopecia have changes limited to only the vessels and hair follicles, respectively. It is critical to recognize that a relatively limited number of histologic patterns are seen in a large array of clinical entities. Therefore, clinicopathologic correlation and careful examination of histologic details are of the utmost importance when evaluating skin biopsies for inflammatory disorders.
Subject(s)
Dermatitis/pathology , Skin/pathology , Biopsy , Child , Dermatitis/diagnosis , Dermatitis/etiology , HumansABSTRACT
BACKGROUND: A novel coaxial biopsy system powered by a handheld drill has recently been introduced for percutaneous bone biopsy. This technical note describes our initial experience performing fluoroscopy-guided vertebral body biopsies with this system, compares the yield of drill-assisted biopsy specimens with those obtained using a manual technique, and assesses the histologic adequacy of specimens obtained with drill assistance. METHODS: Medical records of all single-level, fluoroscopy-guided vertebral body biopsies were reviewed. Procedural complications were documented according to the Society of Interventional Radiology classification. The total length of bone core obtained from drill-assisted biopsies was compared with that of matched manual biopsies. Pathology reports were reviewed to determine the histologic adequacy of specimens obtained with drill assistance. RESULTS: Twenty eight drill-assisted percutaneous vertebral body biopsies met study inclusion criteria. No acute complications were reported. Of the 86 % (24/28) of patients with clinical follow-up, no delayed complications were reported (median follow-up, 28 weeks; range 5-115 weeks). The median total length of bone core obtained from drill-assisted biopsies was 28 mm (range 8-120 mm). This was longer than that obtained from manual biopsies (median, 20 mm; range 5-45 mm; P = 0.03). Crush artifact was present in 11 % (3/28) of drill-assisted biopsy specimens, which in one case (3.6 %; 1/28) precluded definitive diagnosis. CONCLUSIONS: A drill-assisted, coaxial biopsy system can be used to safely obtain vertebral body core specimens under fluoroscopic guidance. The higher bone core yield obtained with drill assistance may be offset by the presence of crush artifact.
Subject(s)
Image-Guided Biopsy/instrumentation , Radiology, Interventional/methods , Spinal Diseases/pathology , Adult , Aged , Aged, 80 and over , Artifacts , Female , Fluoroscopy , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Positron-Emission Tomography , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
The OnControl coaxial biopsy system (Vidacare Corporation, Shavano Park, TX) includes an inner diamond-tipped access needle and hollow biopsy needle that engage with a battery-powered hand drill. Herein, we report the use of this novel device to perform two CT-guided percutaneous skull biopsies. Both procedures were performed without complication and facilitated a pathologic diagnosis.
Subject(s)
Fibrous Dysplasia of Bone/pathology , Image-Guided Biopsy/instrumentation , Lymphoma, B-Cell/pathology , Tomography, X-Ray Computed , Aged, 80 and over , Equipment Design , Female , Humans , Male , Middle AgedABSTRACT
Stereotactic radiosurgery and percutaneous radiofrequency ablation are emerging therapies for pain palliation and local control of spinal metastases. However, the post-treatment imaging findings are not well characterized and the risk of long-term complications is unknown. We present the case of a 46-year-old woman with delayed vertebral body collapse after stereotactic radiosurgery and radiofrequency ablation of a painful lumbar metastasis. Histopathologic-MRI correlation confirmed osteonecrosis as the underlying etiology and demonstrated that treatment-induced vascular fibrosis and tumor progression can have identical imaging appearances.
Subject(s)
Catheter Ablation , Fractures, Compression/etiology , Leiomyosarcoma/surgery , Postoperative Complications/etiology , Radiosurgery , Spinal Fractures/etiology , Spinal Neoplasms/surgery , Fatal Outcome , Female , Fluorodeoxyglucose F18 , Fractures, Compression/diagnostic imaging , Fractures, Compression/surgery , Humans , Image-Guided Biopsy , Leiomyosarcoma/diagnostic imaging , Leiomyosarcoma/secondary , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Magnetic Resonance Imaging , Middle Aged , Pain Measurement , Positron Emission Tomography Computed Tomography , Postoperative Complications/diagnostic imaging , Postoperative Complications/surgery , Radiopharmaceuticals , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/secondaryABSTRACT
Human T-cell lymphotropic virus type 1 is associated with adult T-cell leukemia/lymphoma (ATLL). Published series of ATLLs seen at a United States medical institution are rare. We present the features of 4 ATLLs diagnosed at our North American tertiary care medical center from 1990 to 2012. Despite the absence of a history of origin from an endemic region, all our ATLLs demonstrated evidence of human T-cell lymphotropic virus type 1 infection. Central nervous system (CNS) involvement by ATLL was uncommon in our series, and represented only 1.6% (1/64) of all CNS B-cell or T-cell lymphomas diagnosed over a 20+ year period at our institution. Review of the medical literature reveals that the majority of CNS-involved ATLLs present with the lymphoma or acute subtype, and complete remission is difficult to achieve in these cases. CNS involvement frequently occurs with a systemic disease, which carries an aggressive clinical course with poor prognosis. In addition, CNS involvement by ATLL can be the initial presentation or seen with relapsed disease, can be the only site or be associated with other tissue sites of involvement, and may manifest with variable clinical signs/symptoms. Our retrospective study reveals that ATLLs are rare mature T-cell lymphomas in a native North American population, but the clinical and histopathologic features of ATLLs from this nonendemic region are similar to those seen from other endemic regions. Early recognition of these rare ATLLs involving uncommon sites, such as the CNS, will help optimize treatment for these infrequent mature T-cell lymphomas.
Subject(s)
Central Nervous System Neoplasms/pathology , HTLV-I Infections/pathology , Leukemia-Lymphoma, Adult T-Cell/pathology , Adult , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Central Nervous System Neoplasms/chemistry , Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/therapy , Central Nervous System Neoplasms/virology , Early Detection of Cancer , Fatal Outcome , Female , Gene Rearrangement , Genes, T-Cell Receptor gamma , HTLV-I Infections/complications , HTLV-I Infections/virology , Human T-lymphotropic virus 1/isolation & purification , Humans , Leukemia-Lymphoma, Adult T-Cell/genetics , Leukemia-Lymphoma, Adult T-Cell/metabolism , Leukemia-Lymphoma, Adult T-Cell/therapy , Leukemia-Lymphoma, Adult T-Cell/virology , Male , Middle Aged , Missouri , Predictive Value of Tests , Retrospective Studies , Tertiary Care Centers , Time Factors , Treatment OutcomeABSTRACT
T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive mature T-cell leukemia with frequent cutaneous presentation, which has not been well characterized. Among the 25 T-PLLs diagnosed between 1990 and 2013 at our institution, 32% (8/25) showed cutaneous manifestations, presenting as rash, purpura, papules, and ulcers. The skin biopsies showed leukemia cutis with perivascular and periadnexal irregular, small to medium-sized lymphoid infiltrates without epidermotropism. The lymphoid infiltrates were composed of mature CD4+ T cells expressing other T-cell antigens, and a subset (48%) showed dual CD4+/CD8+ coexpression. Higher median absolute peripheral blood lymphocyte count (43.0 vs. 13.0 k/mm; P=0.031) and elevated lactate dehydrogenase levels (P=0.00018) at the time of diagnosis were significantly associated with T-PLLs with skin involvement compared with those without. The extent of bone marrow involvement (P=0.849) and overall survival (P=0.144) was similar in the 2 groups. Fluorescence in situ hybridization or karyotype revealed frequent gains of MYC (67%; n=9), loss of ATM (64%; n=11), and TCL1A rearrangement or inversion 14q (75%; n=12). Gains of TCL1A was also seen (78%; n=9), including in some cases that had concurrent TCL1A rearrangement, whereas TP53 loss was less common (30%; n=10). No correlation was seen between the immunophenotype and morphology versus the presence or absence of skin involvement. These data suggest that cutaneous involvement by T-PLL is relatively common and often associated with significant peripheral blood involvement. The frequent MYC, ATM, and TCL1A alterations identified support that these genes are integral to the pathogenesis of T-PLL.