Dongsi Lu

Washington University in St. Louis, San Luis, Missouri, United States

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Publications (11)28.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Activating mutations in BRAF have been observed in up to 60% of melanomas, indicating a pivotal role for kinase deregulation in tumor progression. Vemurafenib is a specific inhibitor of BRAF for treatment of melanomas with activating BRAF V600E mutations and has been a major advancement in melanoma treatment. Treatment with vemurafenib, and to a lesser extent, sorafenib, a relatively non-specific inhibitor of BRAF, has been associated with cutaneous squamous cell carcinoma.Methods Clinical and microscopic characteristics of cutaneous neoplasms were evaluated following vemurafenib administration.ResultsTwenty-four of forty-seven (51%) patients receiving vemurafenib at our institution developed 146 total cutaneous neoplasms, with 75% developing multiple lesions. The median number of lesions in affected patients was three. Body distribution included head/neck (29%), chest/back (21%), upper (23%) and lower extremities (27%). Lesions were biopsied and pathologically demonstrated multiple types of epidermal tumors including, but not limited to: verrucous keratoses with/without partial thickness dysplasia, actinic keratoses, and well-differentiated and invasive squamous cell carcinomas with/without keratoacanthomatous features.Conclusions We describe the histopathologic findings of skin lesions potentially associated with vemurafenib. Additional investigation is necessary to further elucidate cutaneous neoplasms associated with vemurafenib; however, frequent dermatologic evaluation is warranted in all patients receiving BRAF inhibitors.
    Journal of Cutaneous Pathology 03/2014; · 1.77 Impact Factor
  • International journal of dermatology 12/2013; 52(12):1586-1588. · 1.18 Impact Factor
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    ABSTRACT: The malignant peripheral nerve sheath tumor is a relatively uncommon type of soft tissue sarcoma arising from a peripheral nerve or extraneural soft tissues and showing nerve sheath differentiation. The diagnosis of malignant peripheral nerve sheath tumor is one of the most challenging tasks in surgical pathology because of its uncommon type (5-10% soft tissue sarcomas), morphologic resemblance to other spindle cell neoplasms and lack of sensitive and specific immunohistochemical markers. The pathologic diagnosis is more straightforward in the clinical setting of neurofibromatosis-1, but problems are mainly centered on the non-neurofibromatosis-1 malignant peripheral nerve sheath tumors. To date, S100 protein is the most widely applied marker in the case of a suspected malignant peripheral nerve sheath tumor, yet its suboptimal sensitivity and its expression in other spindle cell neoplasms, including spindle cell melanoma, clear-cell sarcoma, leiomyosarcoma and monophasic synovial sarcoma, add to the diagnostic conundrum. Growth-associated protein 43 (GAP43), a membrane-associated phosphoprotein expressed in neuronal growth cones and Schwann cell precursors during neural development and axonal regeneration, was applied to a set of nerve sheath and non-nerve sheath spindle cell neoplasms. The findings in this study indicate that GAP43 is expressed in malignant peripheral nerve sheath tumors (n=18/21; 86%) and demonstrates a sensitivity superior to S100 protein (n=13/21; 62%). GAP43 is also positive in neurofibromas (n=17/18; 94%), schwannomas (n=11/12; 92%) and desmoplastic melanomas (n=7/10; 70%). In contrast, it is negative in the non-desmoplastic spindle cell melanomas (n=20/22; 91%). Of the other non-neural soft tissue sarcomas, GAP43 is non-reactive in most leiomyosarcomas (n=14/16; 88%) and clear-cell sarcomas (n=8/8), and only focally positive in monophasic synovial sarcomas (n=3/7; 43%). GAP43 is seemingly a highly sensitive marker for peripheral nerve sheath tumors and may serve as a useful diagnostic adjunct in the diagnosis of malignant peripheral nerve sheath tumor from other spindle cell neoplasms, including spindle cell melanoma.Modern Pathology advance online publication, 26 July 2013; doi:10.1038/modpathol.2013.128.
    Modern Pathology 07/2013; · 5.25 Impact Factor
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    ABSTRACT: BACKGROUND: Sebaceous carcinoma represents a rare and potentially fatal adnexal malignancy. Poorly-differentiated sebaceous carcinoma consisting of infiltrative basaloid tumor cells with inapparent lipid vesicles can mimic basal cell carcinoma (BCC). Conversely, other epithelial tumors can exhibit clear cell histopathology and mimic sebaceous carcinoma. At the present time, immunohistochemical markers unique for sebaceous carcinoma are limited. METHODS: We evaluated the expression of three lipid synthesis/processing protein markers alpha/beta hydrolase domain-containing protein 5 (ABHD5), progesterone receptor membrane component-1 (PGRMC1) and squalene synthase (SQS) in sebaceous carcinoma and investigated their utility in differentiating sebaceous tumors from BCC with clear cell features. Immunohistochemistry was performed on 23 sebaceous carcinomas, 14 sebaceomas and 14 BCCs with clear cell features. RESULTS: In sebaceous carcinomas, ABHD5 showed dispersed, cytoplasmic punctate and/or vesicular staining (n = 19/23, 83%), while PGRMC1 and SQS each showed vesicular and membranous staining in tumor cells (n = 22/23, 96%). In all sebaceomas, these markers highlighted tightly clustered lipid vesicles in sebocytes. All BCCs with clear cell features were negative for these three markers. CONCLUSION: ABHD5, PGRMC1 and SQS are novel markers for sebaceous carcinoma and can reliably distinguish sebaceous neoplasms from non-sebaceous tumors, specifically BCC with clear cell features.
    Journal of Cutaneous Pathology 04/2013; · 1.77 Impact Factor
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    ABSTRACT: Sentinel lymph node evaluation is a critical component of melanoma staging, and lymph node status provides one of the most powerful predictors of melanoma recurrence and survival. One of the well-known diagnostic pitfalls in melanoma sentinel lymph node evaluation is the presence of nodal melanocytic nevi, which has been demonstrated in up to 26% of lymphadenectomy specimens and specifically in melanoma patients. Melanocytic markers enhance the sensitivity of melanoma detection in sentinel lymph nodes. However, established markers such as anti-melan-A/MART1, S100 protein and SOX10 antibodies cannot discriminate melanoma metastasis from nodal nevi. Recent studies have demonstrated strong expression of neural stem/progenitor cell markers nestin and SOX2 in melanoma. In this study, we tested the diagnostic utility of nestin and SOX2 in differentiating metastatic melanomas from nodal nevi. Twenty-three lymph nodes with metastatic melanomas and 17 with nodal nevi were examined. Of the 23 metastatic melanomas, 18 showed diffuse and strong (3+) nestin, 4 showed rare cells with strong (3+) nestin, and one showed diffuse but faint (1+) nestin staining. Nuclear SOX2 was positive in 13 metastatic melanomas. In contrast, 15 nodal nevi showed no nestin, and 2 showed rare cells with very faint (<1+) nestin staining. SOX2 was negative in 13 nodal nevi. Overall, nestin was strongly expressed in metastatic melanomas (n=22/23; 96%), but not in nodal melanocytic nevi (n=15/17; 88%; P<0.0001). SOX2 was also expressed in metastatic melanomas (n=13/23; 57%) but not in the majority of nodal melanocytic nevi (n=13/16; 81%; P=0.02). In one lymph node harboring metastatic melan-A-negative desmoplastic melanoma, nestin and SOX2 strongly highlighted the infiltrating tumor cells, suggesting the potential clinical value of these two markers in desmoplastic melanoma lymph node biopsies. This study provides evidence that nestin and SOX2 can effectively differentiate nodal melanocytic nevi from metastatic melanomas and serve as powerful diagnostic adjuncts in melanoma staging.Modern Pathology advance online publication, 17 August 2012; doi:10.1038/modpathol.2012.132.
    Modern Pathology 08/2012; · 5.25 Impact Factor
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    ABSTRACT: Neurotized melanocytic nevi and neurofibromas are common, benign cutaneous neoplasms. Usually they are histologically distinct from each other; however, neurotized melanocytic nevi and neurofibromas can be clinically and histologically similar. To determine whether Melan-A (MART-1) immunohistochemical stain is sufficient to differentiate neurotized melanocytic nevi from neurofibromas. Forty-nine consecutive specimens of melanocytic nevi with neurotization and 49 specimens of neurofibromas were selected. We used antibodies against Melan-A, S100, and neurofilament protein. All of the melanocytic nevi showed Melan-A staining within the neurotized areas, with most of the areas staining strongly positive, whereas all the neurofibromas were completely absent of Melan-A stain. All of the nevi, including the neurotized areas, stained strongly and diffusely for S100, whereas all the neurofibromas showed a distinctive, sharp, wavy pattern of S100 staining. Neurofilament protein showed scattered staining of both melanocytic nevi and neurofibromas. Our data indicate that Melan-A immunohistochemical staining is helpful in differentiating neurotized melanocytic nevi from neurofibromas when distinction on histomorphology alone is difficult.
    Archives of pathology & laboratory medicine 07/2012; 136(7):810-5. · 2.78 Impact Factor
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    ABSTRACT: BACKGROUND: Visceral malignancy has been associated with sebaceous neoplasms in patients with Muir-Torre syndrome. However, no large studies have been done to evaluate the frequency of visceral tumors in patients with sebaceous neoplasms and mismatch repair (MMR) protein expression of the sebaceous tumors. OBJECTIVE: We sought to determine the frequency of visceral tumors in patients with sebaceous neoplasms, MMR protein expression of the sebaceous tumors, and the related surveillance practices of physicians. METHODS: We identified 85 patients with sebaceous neoplasms. Relevant clinical information was obtained via chart review and database searches. MMR protein expression was examined by immunohistochemistry. RESULTS: Nineteen of the 85 patients had a total of 22 visceral malignancies, of which 41% were genitourinary in origin. Ten of the 17 patients (59%) with visceral malignancy had loss of MMR expression in their sebaceous neoplasms or somatic MMR mutation. Thirty patients had other findings such as colonic adenomas and polyps. Of the 23 patients who had a family history of visceral malignancy, 9 had a personal history of visceral malignancy. LIMITATIONS: Only one sebaceous tumor from each patient (except one) was tested for MMR, which might reduce the sensitivity. CONCLUSION: Our findings demonstrate an increased frequency of internal malignancy in patients with sebaceous neoplasms compared with the general population, and highlight the heterogeneous nature of the visceral tumors. A majority of the sebaceous tumors show loss of MMR expression. The study reminds us to strive toward a consistent and comprehensive approach to screening for internal malignancy when a patient is given a diagnosis of a sebaceous neoplasm.
    Journal of the American Academy of Dermatology 04/2012; · 4.91 Impact Factor
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    ABSTRACT: Although most cases of intravascular large cell lymphoma exhibit a B-cell phenotype, less than 50 cases in the literature describe a T-cell or natural killer cell phenotype and, of these, the majority are CD3+, CD4-, CD5-, CD30-, CD56+, TIA-1+, and EBER+. We present a case of a rare intravascular large T-cell lymphoma in a 59-year-old man with an unusual CD3+, CD4+, CD5-, CD30+, CD56-, TIA-1-negative and EBER-negative phenotype. This T helper or CD30 phenotype is particularly uncommon. To our knowledge, it has only been described once before and never in the absence of the cytotoxic marker TIA-1. This case exemplifies the particular diagnostic challenges raised by intravascular large cell lymphomas generally and should encourage the use of endothelial immunohistochemical staining in questionable cases. While evaluating skin punch biopsies, it is critical to keep this rare entity on the differential diagnosis along with the relatively more common intravascular large B-cell lymphoma and epithelial malignancies. Additionally, our understanding of intravascular large natural killer/T-cell lymphoma as a heterogeneous phenotypic entity continues to evolve. This case demonstrates that the degree of this phenotypic heterogeneity may be even greater than previously thought.
    The American Journal of dermatopathology 12/2011; 33(8):e99-102. · 1.30 Impact Factor
  • Archives of dermatology 06/2010; 146(6):680-1. · 4.76 Impact Factor
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    ABSTRACT: Osseous metaplasia has recently been described in several cases of nephrogenic systemic fibrosis, sometimes in association with unusual clinical features such as painful hyperkeratotic spicules, palpable bony masses, and disease regression. Some authors have suggested that it may mainly occur late in the disease course or even be a marker for involuting nephrogenic systemic fibrosis. Here, we present a 27-year-old woman with a 7-year history of nephrogenic systemic fibrosis, who developed cutaneous osseous metaplasia.
    Dermatology online journal 01/2010; 16(8):3.
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    ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare disorder involving widespread infection with specific human papillomavirus types and characteristic clinical lesions that may resemble verruca plana, tinea versicolor, psoriasis, or seborrheic keratoses. The most common HPV types found in EV are 5, 8, 17, and 20. Histopathologically, lesions demonstrate stereotypical enlarged keratinocytes in the upper epidermis with gray-blue cytoplasm, enlarged round nuclei with pale chromatin, and one or multiple nucleoli. Epidermodysplasia verruciformis may occur in either a classical form (often familial, early onset, and complicated by squamous cell carcinoma) or in association with various hereditary or acquired immunodeficiencies, particularly HIV. Fewer than 20 cases of HIV-associated epidermodysplasia verruciformis have been reported. We describe a 42-year-old HIV-positive man who presented with hypo- and hyperpigmented papules and plaques on the upper trunk, head, and neck, with histopathologic findings of epidermodysplasia verruciformis.
    Dermatology online journal 02/2009; 15(1):1.

Publication Stats

19 Citations
28.96 Total Impact Points

Institutions

  • 2011–2014
    • Washington University in St. Louis
      • Department of Pathology and Immunology
      San Luis, Missouri, United States
  • 2010–2012
    • University of Washington Seattle
      • Division of Dermatology
      Seattle, WA, United States
  • 2009
    • Stanford University
      • Department of Dermatology
      Stanford, CA, United States