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Drazen M Jukic

Publications and source records attributed to Drazen M Jukic.

12 recordsLinked to original sources
PubMed2006

Primary histologic diagnosis using automated whole slide imaging: a validation study.

BACKGROUND: Only prototypes 5 years ago, high-speed, automated whole slide imaging (WSI) systems (also called digital slide systems, virtual microscopes or wide field imagers) are becoming increasingly capable and robust. Modern devices can capture a slide in 5 minutes at spatial sampling periods of less than 0.5 micron/pixel. The capacity to rapidly digitize large numbers of slides should eventually have a profound, positive impact on pathology. It is important, however, that pathologists validate these systems during development, not only to identify their limitations but to guide their evolution. METHODS: Three pathologists fully signed out 25 cases representing 31 parts. The laboratory information system was used to simulate real-world sign-out conditions including entering a full diagnostic field and comment (when appropriate) and ordering special stains and recuts. For each case, discrepancies between diagnoses were documented by committee and a "consensus" report was formed and then compared with the microscope-based, sign-out report from the clinical archive. RESULTS: In 17 of 25 cases there were no discrepancies between the individual study pathologist reports. In 8 of the remaining cases, there were 12 discrepancies, including 3 in which image quality could be at least partially implicated. When the WSI consensus diagnoses were compared with the original sign-out diagnoses, no significant discrepancies were found. Full text of the pathologist reports, the WSI consensus diagnoses, and the original sign-out diagnoses are available as an attachment to this publication. CONCLUSION: The results indicated that the image information contained in current whole slide images is sufficient for pathologists to make reliable diagnostic decisions and compose complex diagnostic reports. This is a very positive result; however, this does not mean that WSI is as good as a microscope. Virtually every slide had focal areas in which image quality (focus and dynamic range) was less than perfect. In some cases, there was evidence of over-compression and regions made "soft" by less than perfect focus. We expect systems will continue to get better, image quality and speed will continue to improve, but that further validation studies will be needed to guide development of this promising technology.

Journal Article↗
PubMed2006

Insulin-like growth factor binding protein 5 induces skin fibrosis: A novel murine model for dermal fibrosis.

OBJECTIVE: To determine the role of insulin-like growth factor binding protein 5 (IGFBP-5) in the development of skin fibrosis in vivo, by examining the effect of overexpression of IGFBP-5 in mouse skin. METHODS: Wild-type C57BL/6J mice were injected subcutaneously with replication-deficient serotype 5 adenovirus expressing human IGFBP-3 (Ad3), IGFBP-5 (Ad5), or no complementary DNA (cAd). Mice were killed 3, 8, or 22 days postinjection. The dermal thickness and dermal collagen bundle thickness in skin sections were measured. The deposition of collagen in the extracellular matrix (ECM) was quantified using the Sircol assay. Expression of proliferating cell nuclear antigen (PCNA) and fibronectin, as determined by immunohistochemical analysis, was used to evaluate fibroblast activation, and vimentin and alpha-smooth muscle actin (alpha-SMA) were used to evaluate the fibroblast phenotype. RESULTS: Adenovirally expressed IGFBP was detected in dermal fibroblasts, endothelial cells, epithelial cells, and muscle bundles in Ad3- and Ad5-injected mice. Increased collagen deposition, denser dermal connective tissue, and increased collagen bundle thickness were observed in IGFBP-5-overexpressing mice. Dermal thickness and collagen bundle thickness were significantly increased in Ad5-injected mice compared with cAd- and Ad3-injected mice. Treatment with Ad5 resulted in a dose-dependent increase in dermal and collagen bundle thickness. Increased deposition of collagen and fibronectin, increased numbers of PCNA-positive fibroblasts, as well as increased numbers of vimentin- and alpha-SMA-double-positive fibroblasts were detected in the dermis of IGFBP-5-overexpressing mouse skin. CONCLUSION: IGFBP-5 is a key mediator of fibrosis. IGFBP-5 mediates its profibrotic effects through fibroblast activation, increased ECM deposition, and myofibroblastic transformation of dermal fibroblasts. Overexpression of IGFBP-5 provides a novel model for studying the pathogenesis of skin fibrosis in systemic sclerosis.

Animals↗
PubMed2006

Use of whole slide imaging in surgical pathology quality assurance: design and pilot validation studies.

By imaging large numbers of slides automatically at high resolution, modem automated whole slide imaging (WSI) systems have the potential to become useful tools in pathology practice. This article describes a pilot validation study for use of automated high-speed WSI systems for surgical pathology quality assurance (QA). This was a retrospective comparative study in which 24 full genitourinary cases (including 47 surgical parts and 391 slides) were independently reviewed with traditional microscopy and whole slide digital images. Approximately half the cases had neoplasia in the diagnostic line. At the end of the study, diagnostic discrepancies were evaluated by a pathology consensus committee. The study pathologists felt that the traditional and WSI methods were comparable for case review. They reported no difference in perceived case complexity or diagnostic confidence between the methods. There were 4 clinically insignificant discrepancies with the signed-out cases: 2 from glass slide and 2 with WSI review. Of the 2 discrepancies reported by the WSI method, the committee agreed with the reviewer once and the original report once. At the end of the study, the participants agreed that automated WSI is a viable potential modality for surgical pathology QA, especially in multifacility health systems that would like to establish interfacility QA. The participants felt that major issues limiting the implementation of WSI-based QA did not involve image acquisition or quality but rather image management issues such as the pathologist's interface, the hospital's network, and integration with the laboratory information system.

Humans↗
PubMed2006

Systemic mastocytosis mimicking inflammatory bowel disease: A case report and discussion of gastrointestinal pathology in systemic mastocytosis.

Gastrointestinal (GI) symptoms are present in up to 80% of patients with systemic mastocytosis (SM). GI symptoms include mainly abdominal pain, diarrhea, nausea, and vomiting. It is believed that most of the GI symptoms are due to the secondary effect of mast cell mediators on the GI tract. Direct involvement of the GI tract by neoplastic mast cell infiltration has not been well documented. We report a case of SM that initially mimicked inflammatory bowel disease based on clinical, radiographic, endoscopic, and histopathologic findings. On routine histologic sections of small bowel and colonic mucosal biopsies, there was expansion of the lamina propria by mononuclear inflammatory cells, foci of erosions with associated acute inflammation, and evidence of chronic mucosal injury with architectural distortion and gland foreshortening. Only on repeat biopsies and with ancillary tests for mast cells was a diagnosis of SM made, with extensive involvement of the GI tract. This is the first reported case of SM presenting as and mimicking inflammatory bowel disease. It is critical that clinicians and pathologists are aware that neoplastic mast cells in patients with SM can infiltrate the mucosa throughout the GI tract and that this infiltration can lead to symptoms and findings that can mimic inflammatory bowel disease.

Colonoscopy↗
PubMed2006

Metastatic basal cell carcinoma: four case reports, review of literature, and immunohistochemical evaluation.

CONTEXT: Metastatic basal cell carcinoma (BCC) is relatively rare and is seldom considered a complication in the routine treatment and follow-up of patients with BCC. Although multiple studies have tried to distinguish aggressive from nonaggressive BCCs, to our knowledge, no consistent clinical, histopathologic, or immunohistochemical features have yet been reported. OBJECTIVE: To report 4 cases of metastatic BCCs and to evaluate these in addition to known nonmetastatic BCCs with specific immunostains in an attempt to find distinct morphologic or immunohistochemical patterns that could be helpful in identifying aggressive BCCs. DESIGN: We reviewed 4 cases of metastatic BCCs and recorded the clinical and morphologic findings. We then searched our archives for 14 cases of BCC that followed the usual nonaggressive course. We evaluated these 18 cases with immunohistochemical stains for Ki-67, p53, and bcl-2. RESULTS: In metastasizing BCC, Ki-67 staining was slightly higher in metastatic sites than in primary sites (average 63% and 51%, respectively). p53 was expressed in 3 of 4 primary sites and 2 of 4 metastatic sites. Bcl-2 was positive in both primary and metastatic sites in 3 of 4 cases. In the 14 cases of nonaggressive BCC, staining for Ki-67 averaged 38%, p53 was positive in 11 cases, and Bcl-2 staining was noted in 13 cases. CONCLUSIONS: Overall, in the small sample that we evaluated, the immunohistochemical markers for Ki-67, p53, and Bcl-2 did not distinguish between metastatic and nonaggressive BCCs.

Adult↗
PubMed2006

Scalp metastasis from esophageal adenocarcinoma.

There are few reported cases of cutaneous metastases of esophageal carcinoma, especially of esophageal adenocarcinoma, but reports may become more common as the incidence of esophageal cancer increases. We present a case of a 67-year-old man with metastatic esophageal cancer in the scalp. Clinical and histologic findings are discussed, and recommendations for clinicians are suggested.

Adenocarcinoma↗
PubMed2006

Hereditary basaloid follicular hamartoma syndrome.

Basaloid follicular hamartoma syndrome (BFHS) is a rare adnexal tumor genodermatosis. We present a case of hereditary BFHS and review the literature concerning the clinical and histologic features of this entity.

Aged↗
PubMed2005

Rash and pancytopenia as initial manifestations of acute graft-versus-host disease after liver transplantation.

Acute graft-versus-host disease is mainly a complication of allogeneic bone-marrow transplantation, and rarely seen after transplantation of solid organs. We describe a 68-year-old man who developed a maculopapular eruption and fever approximately 15 days after orthotopic liver transplantation for cryptogenic cirrhosis. At day 19, the patient developed abrupt neutropenia and diarrhea. Skin biopsy was performed and the specimen revealed basal cell layer vacuolization, necrotic keratinocytes, and satellite cell necrosis. Bone-marrow aspiration performed after the patient became pancytopenic revealed aplastic marrow with scattered lymphocytes and rare megakaryocytes. A diagnosis of acute graft-versus-host disease was made and an immunosuppressive drug regimen was initiated. Unfortunately, the patient died after support was withdrawn because of total ablation of his bone marrow and multiorgan failure. This report describes the rare presentation of acute graft-versus-host disease after solid organ transplantation, and that skin manifestations may be an early presenting sign.

Aged↗
PubMed2003

Fluorescence imaging analysis of upstream regulators and downstream targets of STAT3 in melanoma precursor lesions obtained from patients before and after systemic low-dose interferon-alpha treatment.

Atypical nevi are the precursors and risk markers of melanoma. Apart from persistently monitoring these nevocytic lesions and resecting them at the earliest signs of clinical changes, there is as yet no systemic clinical treatment available to interfere with their progression to melanoma. To explore clinical treatments that might interfere with and possibly prevent atypical nevus progression, a previous study documented that 3 months systemic low-dose interferon-alpha (IFN-alpha) treatment of patients with a clinical history of melanoma and numerous atypical nevi, led to inactivation of the STAT1 and STAT3 transcription factors in atypical nevi. Based upon this finding, we initiated a second study to determine whether systemic low-dose IFN-alpha treatment also impairs the expression of upstream regulators and downstream targets of STAT1 and STAT3 in atypical nevi. Using cyanine dye-conjugated antibodies, fluorescence imaging analysis revealed expression of JAK2, JNK1, AKT1, NF-kappa B, and IFN-alpha/beta receptor in benign and atypical nevi, and early- and advanced-stage melanomas. To determine possible changes in the level of expression of these molecules in atypical nevi, excised before and after 3 months of systemic low-dose IFN-alpha treatment, newly designed optical imaging software was used to quantitate the captured fluorescent hybridization signals on a cell-by-cell basis and across an entire nevus section. The results of this analysis did not provide evidence that systemic low-dose IFN-alpha treatment alters the level of expression of upstream regulators or downstream targets of STAT1 and STAT3.

DNA-Binding Proteins↗
PubMed2002

Atrophic dermatofibroma: a case report and review of the literature.

BACKGROUND: Atrophic dermatofibroma is an uncommon variant of dermatofibroma. It lacks the classic clinical features of a dermatofibroma and is often misdiagnosed. OBJECTIVE: To describe the clinical and histologic features of atrophic dermatofibroma. METHODS: Case report and review of the literature. RESULTS: A 45-year-old white woman was found to have a 7 mm x 5 mm atrophic, depressed lesion in the right axilla. A clinical diagnosis of anetoderma was made and the lesion was excised with minimal margins. Histopathologic examination revealed findings consistent with dermatofibroma. However, focal CD34 staining and involvement of superficial subcutaneous tissue raised concern regarding an early dermatofibrosarcoma protuberans developing in a dermatofibroma. The patient underwent Mohs micrographic surgery (MMS) for definitive treatment. The final diagnosis is thought to be atrophic dermatofibroma. Reported cases in the English language literature are reviewed and the clinical and histopathologic findings are described. CONCLUSION: Atrophic dermatofibroma is a well-described, yet uncommon, variant of dermatofibroma. It is often clinically misdiagnosed, and histopathologic evaluation can be misleading. The clinician and pathologist should consider this diagnosis in the evaluation of atrophic, depressed lesions.

Antigens, CD34↗