Jody Hooper | Johns Hopkins University (original) (raw)

Papers by Jody Hooper

Autopsy and Case Reports, 2020

Journal of Gastrointestinal and Liver Diseases, 2017

Autopsy in the 21st Century, 2018

The concept of utilizing autopsy as a unique opportunity for tissue sampling is spreading across ... more The concept of utilizing autopsy as a unique opportunity for tissue sampling is spreading across the United States and internationally. Rapid autopsies are unique in their ability to provide tissue specimens in large volumes and can sample across numerous anatomic locations simultaneously. This chapter will review practical considerations in development, growth, and maintenance of a rapid autopsy program. Best practices for collaboration with researchers, composition of rapid autopsy teams, autopsy logistics and procedures, and sample collection techniques will be explained. Rapid autopsy represents not only an extraordinary opportunity for research but also can provide a fulfilling contribution by patients and their families.

Academic Pathology, 2018

A vertically and horizontally well-integrated quality improvement team is essential for effective... more A vertically and horizontally well-integrated quality improvement team is essential for effective quality data collection and implementation of improvement measures. We outline the quality structure of a large academic pathology department and describe successful projects across multiple divisions made possible by this tightly integrated structure. The physician vice chair for quality organizes departmental quality efforts and provides representation at the hospital level. The department has an independent continuous quality improvement unit and each laboratory of the department has a staff quality improvement representative. Faculty and staff experts have interacted to produce improvements such as accurate container labeling, efficient triage of specimens, and reduction of unnecessary testing. Specialized task forces such as the Courier Task Force are producing concrete recommendations for process improvement. All phases of pathology patient care are represented by faculty and staff who are trained in quality improvement, and each position touches and communicates actively with levels above and below itself. The key to the department's approach has been the daily attention to quality efforts in all of its activities and the close association of faculty and staff to accomplish the goals of greater efficiency, safety, and cost savings.

Academic pathology

Autopsy has been a foundation of pathology training for many years, but hospital autopsy rates ar... more Autopsy has been a foundation of pathology training for many years, but hospital autopsy rates are notoriously low. At the 2014 meeting of the Association of Pathology Chairs, some pathologists suggested removing autopsy from the training curriculum of pathology residents to provide additional months for training in newer disciplines, such as molecular genetics and informatics. At the same time, the American Board of Pathology received complaints that newly hired pathologists recently certified in anatomic pathology are unable to perform an autopsy when called upon to do so. In response to a call to abolish autopsy from pathology training on the one hand and for more rigorous autopsy training on the other, the Association of Pathology Chairs formed the Autopsy Working Group to examine the role of autopsy in pathology residency training. After 2 years of research and deliberation, the Autopsy Working Group recommends the following:Autopsy should remain a component of anatomic patholo...

Archives of pathology & laboratory medicine, 2007

Coccidioidomycosis is a fungal infection contracted through the inhalation of airborne spores, wh... more Coccidioidomycosis is a fungal infection contracted through the inhalation of airborne spores, which are most frequently present in desert areas of the southwestern United States and Mexico. Primary immune response to infection is by T(H)1, a subset of helper T cells. Although pulmonary symptoms are most common, hematogenous systemic spread can also occur. Pregnancy is a well-noted risk factor for disseminated Coccidioides infection. The objective of this review is to provide an overview of coccidioidomycosis and to review immunologic and hormonal factors that increase risk of dissemination in pregnancy. Dissemination may occur more frequently in pregnant patients than in nonpregnant women because of shifts in T-cell immunity, changes in cytokine production, and increased hormone levels. There is disagreement regarding the precise incidence of systemic spread in pregnancy, but most sources agree that risk is substantially increased and vigilance must be high in patients with exposur...

Sarcoma, 2013

A rare sclerosing variant of rhabdomyosarcoma characterized by prominent hyalinization and pseudo... more A rare sclerosing variant of rhabdomyosarcoma characterized by prominent hyalinization and pseudovascular pattern has recently been described as a subtype biologically distinct from embryonal, alveolar, and pleomorphic forms. We present cytogenetic and molecular findings as well as experimental studies of an unusual case of sclerosing rhabdomyosarcoma. The primary lesion arose within the plantar subcutaneous tissue of the left foot of an otherwise healthy 23-year-old male who eventually developed pulmonary nodules despite systemic chemotherapy. Two genetic abnormalities identified in surgical and/or autopsy samples of the tumor were introduced into 10T1/2 murine fibroblasts to determine whether these genetic changes cooperatively facilitated transformation and growth. Cytogenetic analysis revealed a complex abnormal hyperdiploid clone, andMDM2gene amplification was confirmed by fluorescence in situ hybridization. Cancer gene mutation screening using a combination of multiplexed PCR ...

Liver Transplantation, 2003

Fibrosing cholestatic hepatitis is a deleterious manifestation of hepatitis B virus infection in ... more Fibrosing cholestatic hepatitis is a deleterious manifestation of hepatitis B virus infection in immunocompromised patients. Without treatment, this condition is usually fatal within weeks of onset. Liver retransplantation has not been successfully performed to date, and treatment intervention was generally unsuccessful before the advent of adefovir dipivoxil. However, concerns have been expressed about the use of this agent in patients who are renally compromised. A 40-year-old liver transplant recipient with hepatitis B virus reinfection, resistance to lamivudine, and fibrosing cholestatic hepatitis complicated by terminal renal impairment and spontaneous bacterial peritonitis was treated with adefovir dipivoxil 10 mg after every dialysis. Since initiating treatment with adefovir dipivoxil 10 mg, a dramatic virologic and clinical improvement was observed in this patient. The patient returned to work full-time within 6 months of starting adefovir dipivoxil without the need for liver retransplantation. Serum HBV DNA (Amplicor HBV; Roche Diagnostics, Basle, Switzerland) decreased by 6 log 10 copies/mL and became negative (< 400 copies/mL) within 8 weeks of treatment and remains negative at the last available assessment. The patient continues to require renal dialysis, but is generally well. Creatinine clearance improved from 8 mL/min to 16 mL/min during the course of treatment. No adverse events related to adefovir dipivoxil were observed. Adefovir dipivoxil resulted in significant clinical improvement in this patient with hepatitis B virus-induced fibrosing cholestatic hepatitis, despite the presence of renal impairment and lamivudine resistance.

International Urology and Nephrology, 2011

Polyoma virus is a recognized cause of hemorrhagic cystitis, viral nephropathy, and ureteral stri... more Polyoma virus is a recognized cause of hemorrhagic cystitis, viral nephropathy, and ureteral stricture in renal and stem cell transplant recipients. Rarely, polyoma virus causes native kidney and bladder pathology in heavily immunosuppressed patients. We report a unique case of native kidney polyoma virus nephropathy, urothelial ulceration, and renal pelvic fibrosis presenting as a mass lesion in a non-debilitated, apparently immunocompetent man. Based on radiologic, ureterorenoscopic, and urine cytologic findings, a laparoscopic nephrectomy was performed. However, nephrectomy revealed a hemorrhagic scar-like lesion, with urothelial ulceration, but no neoplasm or malignancy. Histopathologic evaluation and immunostaining revealed polyoma viral infection in the nearby renal medulla. This case adds polyoma virus nephropathy to the differential diagnosis of non-neoplastic and reactive masses, which may mimic renal malignancy.

Clinical Imaging, 2014

We report a 57-year-old previously healthy man who presented with dull right upper quadrant pain,... more We report a 57-year-old previously healthy man who presented with dull right upper quadrant pain, weight loss, fatigue, and night sweats. Computed tomography demonstrated a large, heterogeneously enhancing, soft tissue mass with no macroscopic fat above the right kidney with tumor thrombus extending into the inferior vena cava and right atrium. Positron Emission Tomography scanning demonstrated intense Fluorodeoxyglucose avidity in the primary tumor and tumor thrombus. The presumptive radiological diagnosis was adrenocortical carcinoma, but surgical pathology revealed a dedifferentiated liposarcoma. We conclude that suprarenal retroperitoneal liposarcoma should be included in the differential diagnosis for an apparent adrenal mass with venous invasion.

Journal of Thoracic Oncology, 2017

in Fig. 2). From the chest phantom, the bigger registration errors (DTA2mm) came from normal-4mm,... more in Fig. 2). From the chest phantom, the bigger registration errors (DTA2mm) came from normal-4mm, coarse-3mm and coarse-6mm options and appeared mainly in longitude direction. From the pelvic phantom, the bigger registration errors came from coarse-3mm and coarse-6mm options and appeared mainly in longitude direction too. With the same Acquisition Pitch and Reconstruction Interval options, the 'Bone and Tissue Technique' registration option gave bigger errors while 'Full Image Technique' gave the smallest errors. Conclusion: The different scan options will not affect the dose calculation accuracy on MVCT. Therefore, the faster scan mode (coarse+6mm) is recommended for ART plan evaluation. While in position correction of IGRT, normal+2mm option is recommended and the 'Full Image Technique' may improve the registration accuracy. Manual registration correction is necessary after automatic registrations.

Tumor Biology, 2019

M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenviron... more M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported infiltration of M2 macrophages in metastatic castrate-resistant prostate cancers (mCRPC). The objective of this study was to determine whether the extent of M2 macrophage infiltration correlates with prostate cancer aggressiveness, we applied immunohistochemistry to normal prostatic tissue, localized prostate cancer and metastatic castrate-resistant prostate cancer (mCRPC) from 192 patients. To assess M2 macrophage involvement, we analytically validated an IHC assay to detect the human mannose receptor (CD206). Also, we used multiplex immunofluorescent staining to show that a small fraction of CD206 staining co-localizes with endothelial cells of lymphatic vessels, while the vast majority of staining occurs in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion going from normal (i.e. non-inflammation) prostatic tissue, to primary untreated carcinomas, to hormone naive regional lymph node metastases to castration resistant prostate cancer. Complimentary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Altogether, this study revealed a progressive increase in CD206-positive macrophages from normal prostate to metastatic CRPC. Given the immunosuppressive nature of these cells and lack of clinical success of immunotherapy for prostate cancer patients, our results provide a rationale for therapeutic development to deplete these cells in the prostate cancer microenvironment as a potential method to augment immunotherapeutic approaches in prostate cancer. Citation Format: Jelani C. Zarif, Javier A. Baena-Del Valle, Jessica L. Hicks, Christopher M. Heaphy, Igor Vidal, Jacob Luo, Tamara L. Lotan, Jody E. Hooper, William B. Isaacs, Kenneth J. Pienta, Angelo M. De Marzo. Mannose receptor positive macrophage infiltrate correlates with prostate cancer onset and metastatic castration-resistant disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4582.

European Urology Oncology, 2019

M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenviron... more M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported infiltration of M2 macrophages in metastatic castrate-resistant prostate cancers (mCRPC). The objective of this study was to determine whether the extent of M2 macrophage infiltration correlates with prostate cancer aggressiveness, we applied immunohistochemistry to normal prostatic tissue, localized prostate cancer and metastatic castrate-resistant prostate cancer (mCRPC) from 192 patients. To assess M2 macrophage involvement, we analytically validated an IHC assay to detect the human mannose receptor (CD206). Also, we used multiplex immunofluorescent staining to show that a small fraction of CD206 staining co-localizes with endothelial cells of lymphatic vessels, while the vast majority of staining occurs in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion going from normal (i.e. non-inflammation) prostatic tissue, to primary untreated carcinomas, to hormone na.ve regional lymph node metastases to castration resistant prostate cancer. Complimentary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Altogether, this study revealed a progressive increase in CD206-positive macrophages from normal prostate to metastatic CRPC. Given the immunosuppressive nature of these cells and lack of clinical success of immunotherapy for prostate cancer patients, our results provide a rationale for therapeutic development to deplete these cells in the prostate cancer microenvironment as a potential method to augment immunotherapeutic approaches in prostate cancer.

Applied Immunohistochemistry & Molecular Morphology, 2015

High risk human papillomavirus (HPV) infection is a common cause of oropharyngeal squamous cell c... more High risk human papillomavirus (HPV) infection is a common cause of oropharyngeal squamous cell carcinoma, especially in young male nonsmokers. Accurately diagnosing HPV-associated oral cancers is important, because they have a better prognosis and may be treated differently than smoking-related oral carcinomas. Various methods have been validated to test for high risk HPV in cervical tissue samples and they are in routine clinical use to detect dysplasia before it progresses to invasive disease. Similarly, future screening for HPV-mediated oropharyngeal dysplasia may identify patients before it progresses. Our objective was to compare four of these methods in a retrospective series of 87 oral and oropharyngeal squamous cell carcinomas that had archived fresh-frozen and paraffin-embedded tissue for evaluation. Patient age, gender, smoking history, and tumor location were also recorded. DNA prepared from fresh-frozen tissue was tested for HPV genotypes by multiplex PCR analysis (Diatherix), and high risk HPV screening was done with Hybrid Capture 2 (Qiagen hc2) and Cervista (Hologic). Histologic sections were immunostained for p16 (mtm/Roche). HPV positive outcome was defined as agreement between at least two of the three genetic tests and used for X 2 analysis and calculations of diagnostic predictive value. As expected, high risk HPV-positive oral cancers were most common in the tonsil and base of tongue (oropharynx) of younger male (55 years vs 65 years) (p=0.0002) nonsmokers (p=0.01). Most positive cases were HPV16 (33/36, 92%). Hybrid Capture 2 and Cervista were as sensitive as PCR and had fewer false positives than p16 immunohistochemistry.

Obesity increases significantly cancer risk in various organs. Although this has been recognized ... more Obesity increases significantly cancer risk in various organs. Although this has been recognized for decades, the mechanism through which this happens has never been explained. Here, we show that obese people (BMI ≥30) have on average 55% (95%CI: 46%-66%), 68% (95%CI: 59%-76%), and 39% (95%CI: 29%-49%) larger kidneys, liver, and pancreas, respectively. We also find a significant linear relationship between the increase in organ volume and the increase in cancer risk (P-value<10−12). These results provide a mechanism explaining why obese individuals have higher cancer risk in several organs: the larger the organ volume the more cells at risk of becoming cancerous. These findings are important for a better understanding of the effects that obesity has on cancer risk and, more generally, for the development of better preventive strategies to limit the mortality caused by obesity.

Autopsy in the 21st Century, 2018

The time has come to stop reexamining the past of the autopsy, cease ruminating on former glories... more The time has come to stop reexamining the past of the autopsy, cease ruminating on former glories, and look ahead to what hospital autopsy can become. Autopsy can remain a method for discovery of new disease entities, demonstrate its value in an increasingly outcome-based medical system, and become an essential part of cutting-edge molecular research. For these developments to take place, autopsy pathology as a field must grow to encompass measures such as prompt and electronically searchable synoptic reporting, standardized practice methods and teaching, and harnessing of centralized resources at regional centers. Autopsy practitioners must seek out and embrace new roles in informing public policy, assessing patient safety, and engaging in clinical trials. The editors hope this book imparts the best available knowledge, helps improve skills, and provides inspiration needed for the autopsy to reassert its vital presence in the heart of medicine, for the twenty-first century and beyond. The fate of this invaluable asset to clinical care, education, public policy, and research is up to all of us.

Table S14. Gene ontology analysis. (XLSX 62 kb)

Table S1. Treatment schedule for PDX models. Table S2. Patient history of PDX eRMS models. Table ... more Table S1. Treatment schedule for PDX models. Table S2. Patient history of PDX eRMS models. Table S3. Statistical summary for CTG-1213/POS-13212. Table S4. Statistical summary for CTG1116/POS-13166. Table S5. Statistical summary for CTG-1628/POS-132166B. Table S6. Statistical summary for J0103366/CF-13A. Table S7. Histological markers of differentiation in PDX eRMS (CTG-1213) mice. Table S8. Patient history of PDX pleoRMS models. Table S9. Statistical summary for CTG-1213/POS-13212. Table S10. Statistical summary for CTG1116/POS-13166. Table S11. Statistical summary for CTG-1628/POS-132166B. Table S12. Histological markers of differentiation in PDX pleoRMS (CTG-800) mice. Table S13. Primers for RT-PCR. (DOCX 41 kb)

Figure S5. Representative immunohistochemistry for CD68 of mouse eRMS tissue and primary cells. N... more Figure S5. Representative immunohistochemistry for CD68 of mouse eRMS tissue and primary cells. Necrotic tissue (a) showed few macrophages present, while viable tumor (b) showed a collection of many macrophages. Macrophage presence was observed as being the same for all treatment groups. (TIF 2929 kb)

Figure S4. siRNA-mediated knockdown of HDAC3 in eRMS and aRMS. Analysis of MHC expression in RD, ... more Figure S4. siRNA-mediated knockdown of HDAC3 in eRMS and aRMS. Analysis of MHC expression in RD, Rh30 and HSMM cell lines transfected with siRNA at 100â nM for 72â h, targeting HDAC3. (TIF 510 kb)

Autopsy and Case Reports, 2020

Journal of Gastrointestinal and Liver Diseases, 2017

Autopsy in the 21st Century, 2018

The concept of utilizing autopsy as a unique opportunity for tissue sampling is spreading across ... more The concept of utilizing autopsy as a unique opportunity for tissue sampling is spreading across the United States and internationally. Rapid autopsies are unique in their ability to provide tissue specimens in large volumes and can sample across numerous anatomic locations simultaneously. This chapter will review practical considerations in development, growth, and maintenance of a rapid autopsy program. Best practices for collaboration with researchers, composition of rapid autopsy teams, autopsy logistics and procedures, and sample collection techniques will be explained. Rapid autopsy represents not only an extraordinary opportunity for research but also can provide a fulfilling contribution by patients and their families.

Academic Pathology, 2018

A vertically and horizontally well-integrated quality improvement team is essential for effective... more A vertically and horizontally well-integrated quality improvement team is essential for effective quality data collection and implementation of improvement measures. We outline the quality structure of a large academic pathology department and describe successful projects across multiple divisions made possible by this tightly integrated structure. The physician vice chair for quality organizes departmental quality efforts and provides representation at the hospital level. The department has an independent continuous quality improvement unit and each laboratory of the department has a staff quality improvement representative. Faculty and staff experts have interacted to produce improvements such as accurate container labeling, efficient triage of specimens, and reduction of unnecessary testing. Specialized task forces such as the Courier Task Force are producing concrete recommendations for process improvement. All phases of pathology patient care are represented by faculty and staff who are trained in quality improvement, and each position touches and communicates actively with levels above and below itself. The key to the department's approach has been the daily attention to quality efforts in all of its activities and the close association of faculty and staff to accomplish the goals of greater efficiency, safety, and cost savings.

Academic pathology

Autopsy has been a foundation of pathology training for many years, but hospital autopsy rates ar... more Autopsy has been a foundation of pathology training for many years, but hospital autopsy rates are notoriously low. At the 2014 meeting of the Association of Pathology Chairs, some pathologists suggested removing autopsy from the training curriculum of pathology residents to provide additional months for training in newer disciplines, such as molecular genetics and informatics. At the same time, the American Board of Pathology received complaints that newly hired pathologists recently certified in anatomic pathology are unable to perform an autopsy when called upon to do so. In response to a call to abolish autopsy from pathology training on the one hand and for more rigorous autopsy training on the other, the Association of Pathology Chairs formed the Autopsy Working Group to examine the role of autopsy in pathology residency training. After 2 years of research and deliberation, the Autopsy Working Group recommends the following:Autopsy should remain a component of anatomic patholo...

Archives of pathology & laboratory medicine, 2007

Coccidioidomycosis is a fungal infection contracted through the inhalation of airborne spores, wh... more Coccidioidomycosis is a fungal infection contracted through the inhalation of airborne spores, which are most frequently present in desert areas of the southwestern United States and Mexico. Primary immune response to infection is by T(H)1, a subset of helper T cells. Although pulmonary symptoms are most common, hematogenous systemic spread can also occur. Pregnancy is a well-noted risk factor for disseminated Coccidioides infection. The objective of this review is to provide an overview of coccidioidomycosis and to review immunologic and hormonal factors that increase risk of dissemination in pregnancy. Dissemination may occur more frequently in pregnant patients than in nonpregnant women because of shifts in T-cell immunity, changes in cytokine production, and increased hormone levels. There is disagreement regarding the precise incidence of systemic spread in pregnancy, but most sources agree that risk is substantially increased and vigilance must be high in patients with exposur...

Sarcoma, 2013

A rare sclerosing variant of rhabdomyosarcoma characterized by prominent hyalinization and pseudo... more A rare sclerosing variant of rhabdomyosarcoma characterized by prominent hyalinization and pseudovascular pattern has recently been described as a subtype biologically distinct from embryonal, alveolar, and pleomorphic forms. We present cytogenetic and molecular findings as well as experimental studies of an unusual case of sclerosing rhabdomyosarcoma. The primary lesion arose within the plantar subcutaneous tissue of the left foot of an otherwise healthy 23-year-old male who eventually developed pulmonary nodules despite systemic chemotherapy. Two genetic abnormalities identified in surgical and/or autopsy samples of the tumor were introduced into 10T1/2 murine fibroblasts to determine whether these genetic changes cooperatively facilitated transformation and growth. Cytogenetic analysis revealed a complex abnormal hyperdiploid clone, andMDM2gene amplification was confirmed by fluorescence in situ hybridization. Cancer gene mutation screening using a combination of multiplexed PCR ...

Liver Transplantation, 2003

Fibrosing cholestatic hepatitis is a deleterious manifestation of hepatitis B virus infection in ... more Fibrosing cholestatic hepatitis is a deleterious manifestation of hepatitis B virus infection in immunocompromised patients. Without treatment, this condition is usually fatal within weeks of onset. Liver retransplantation has not been successfully performed to date, and treatment intervention was generally unsuccessful before the advent of adefovir dipivoxil. However, concerns have been expressed about the use of this agent in patients who are renally compromised. A 40-year-old liver transplant recipient with hepatitis B virus reinfection, resistance to lamivudine, and fibrosing cholestatic hepatitis complicated by terminal renal impairment and spontaneous bacterial peritonitis was treated with adefovir dipivoxil 10 mg after every dialysis. Since initiating treatment with adefovir dipivoxil 10 mg, a dramatic virologic and clinical improvement was observed in this patient. The patient returned to work full-time within 6 months of starting adefovir dipivoxil without the need for liver retransplantation. Serum HBV DNA (Amplicor HBV; Roche Diagnostics, Basle, Switzerland) decreased by 6 log 10 copies/mL and became negative (< 400 copies/mL) within 8 weeks of treatment and remains negative at the last available assessment. The patient continues to require renal dialysis, but is generally well. Creatinine clearance improved from 8 mL/min to 16 mL/min during the course of treatment. No adverse events related to adefovir dipivoxil were observed. Adefovir dipivoxil resulted in significant clinical improvement in this patient with hepatitis B virus-induced fibrosing cholestatic hepatitis, despite the presence of renal impairment and lamivudine resistance.

International Urology and Nephrology, 2011

Polyoma virus is a recognized cause of hemorrhagic cystitis, viral nephropathy, and ureteral stri... more Polyoma virus is a recognized cause of hemorrhagic cystitis, viral nephropathy, and ureteral stricture in renal and stem cell transplant recipients. Rarely, polyoma virus causes native kidney and bladder pathology in heavily immunosuppressed patients. We report a unique case of native kidney polyoma virus nephropathy, urothelial ulceration, and renal pelvic fibrosis presenting as a mass lesion in a non-debilitated, apparently immunocompetent man. Based on radiologic, ureterorenoscopic, and urine cytologic findings, a laparoscopic nephrectomy was performed. However, nephrectomy revealed a hemorrhagic scar-like lesion, with urothelial ulceration, but no neoplasm or malignancy. Histopathologic evaluation and immunostaining revealed polyoma viral infection in the nearby renal medulla. This case adds polyoma virus nephropathy to the differential diagnosis of non-neoplastic and reactive masses, which may mimic renal malignancy.

Clinical Imaging, 2014

We report a 57-year-old previously healthy man who presented with dull right upper quadrant pain,... more We report a 57-year-old previously healthy man who presented with dull right upper quadrant pain, weight loss, fatigue, and night sweats. Computed tomography demonstrated a large, heterogeneously enhancing, soft tissue mass with no macroscopic fat above the right kidney with tumor thrombus extending into the inferior vena cava and right atrium. Positron Emission Tomography scanning demonstrated intense Fluorodeoxyglucose avidity in the primary tumor and tumor thrombus. The presumptive radiological diagnosis was adrenocortical carcinoma, but surgical pathology revealed a dedifferentiated liposarcoma. We conclude that suprarenal retroperitoneal liposarcoma should be included in the differential diagnosis for an apparent adrenal mass with venous invasion.

Journal of Thoracic Oncology, 2017

in Fig. 2). From the chest phantom, the bigger registration errors (DTA2mm) came from normal-4mm,... more in Fig. 2). From the chest phantom, the bigger registration errors (DTA2mm) came from normal-4mm, coarse-3mm and coarse-6mm options and appeared mainly in longitude direction. From the pelvic phantom, the bigger registration errors came from coarse-3mm and coarse-6mm options and appeared mainly in longitude direction too. With the same Acquisition Pitch and Reconstruction Interval options, the 'Bone and Tissue Technique' registration option gave bigger errors while 'Full Image Technique' gave the smallest errors. Conclusion: The different scan options will not affect the dose calculation accuracy on MVCT. Therefore, the faster scan mode (coarse+6mm) is recommended for ART plan evaluation. While in position correction of IGRT, normal+2mm option is recommended and the 'Full Image Technique' may improve the registration accuracy. Manual registration correction is necessary after automatic registrations.

Tumor Biology, 2019

M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenviron... more M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported infiltration of M2 macrophages in metastatic castrate-resistant prostate cancers (mCRPC). The objective of this study was to determine whether the extent of M2 macrophage infiltration correlates with prostate cancer aggressiveness, we applied immunohistochemistry to normal prostatic tissue, localized prostate cancer and metastatic castrate-resistant prostate cancer (mCRPC) from 192 patients. To assess M2 macrophage involvement, we analytically validated an IHC assay to detect the human mannose receptor (CD206). Also, we used multiplex immunofluorescent staining to show that a small fraction of CD206 staining co-localizes with endothelial cells of lymphatic vessels, while the vast majority of staining occurs in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion going from normal (i.e. non-inflammation) prostatic tissue, to primary untreated carcinomas, to hormone naive regional lymph node metastases to castration resistant prostate cancer. Complimentary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Altogether, this study revealed a progressive increase in CD206-positive macrophages from normal prostate to metastatic CRPC. Given the immunosuppressive nature of these cells and lack of clinical success of immunotherapy for prostate cancer patients, our results provide a rationale for therapeutic development to deplete these cells in the prostate cancer microenvironment as a potential method to augment immunotherapeutic approaches in prostate cancer. Citation Format: Jelani C. Zarif, Javier A. Baena-Del Valle, Jessica L. Hicks, Christopher M. Heaphy, Igor Vidal, Jacob Luo, Tamara L. Lotan, Jody E. Hooper, William B. Isaacs, Kenneth J. Pienta, Angelo M. De Marzo. Mannose receptor positive macrophage infiltrate correlates with prostate cancer onset and metastatic castration-resistant disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4582.

European Urology Oncology, 2019

M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenviron... more M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported infiltration of M2 macrophages in metastatic castrate-resistant prostate cancers (mCRPC). The objective of this study was to determine whether the extent of M2 macrophage infiltration correlates with prostate cancer aggressiveness, we applied immunohistochemistry to normal prostatic tissue, localized prostate cancer and metastatic castrate-resistant prostate cancer (mCRPC) from 192 patients. To assess M2 macrophage involvement, we analytically validated an IHC assay to detect the human mannose receptor (CD206). Also, we used multiplex immunofluorescent staining to show that a small fraction of CD206 staining co-localizes with endothelial cells of lymphatic vessels, while the vast majority of staining occurs in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion going from normal (i.e. non-inflammation) prostatic tissue, to primary untreated carcinomas, to hormone na.ve regional lymph node metastases to castration resistant prostate cancer. Complimentary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Altogether, this study revealed a progressive increase in CD206-positive macrophages from normal prostate to metastatic CRPC. Given the immunosuppressive nature of these cells and lack of clinical success of immunotherapy for prostate cancer patients, our results provide a rationale for therapeutic development to deplete these cells in the prostate cancer microenvironment as a potential method to augment immunotherapeutic approaches in prostate cancer.

Applied Immunohistochemistry & Molecular Morphology, 2015

High risk human papillomavirus (HPV) infection is a common cause of oropharyngeal squamous cell c... more High risk human papillomavirus (HPV) infection is a common cause of oropharyngeal squamous cell carcinoma, especially in young male nonsmokers. Accurately diagnosing HPV-associated oral cancers is important, because they have a better prognosis and may be treated differently than smoking-related oral carcinomas. Various methods have been validated to test for high risk HPV in cervical tissue samples and they are in routine clinical use to detect dysplasia before it progresses to invasive disease. Similarly, future screening for HPV-mediated oropharyngeal dysplasia may identify patients before it progresses. Our objective was to compare four of these methods in a retrospective series of 87 oral and oropharyngeal squamous cell carcinomas that had archived fresh-frozen and paraffin-embedded tissue for evaluation. Patient age, gender, smoking history, and tumor location were also recorded. DNA prepared from fresh-frozen tissue was tested for HPV genotypes by multiplex PCR analysis (Diatherix), and high risk HPV screening was done with Hybrid Capture 2 (Qiagen hc2) and Cervista (Hologic). Histologic sections were immunostained for p16 (mtm/Roche). HPV positive outcome was defined as agreement between at least two of the three genetic tests and used for X 2 analysis and calculations of diagnostic predictive value. As expected, high risk HPV-positive oral cancers were most common in the tonsil and base of tongue (oropharynx) of younger male (55 years vs 65 years) (p=0.0002) nonsmokers (p=0.01). Most positive cases were HPV16 (33/36, 92%). Hybrid Capture 2 and Cervista were as sensitive as PCR and had fewer false positives than p16 immunohistochemistry.

Obesity increases significantly cancer risk in various organs. Although this has been recognized ... more Obesity increases significantly cancer risk in various organs. Although this has been recognized for decades, the mechanism through which this happens has never been explained. Here, we show that obese people (BMI ≥30) have on average 55% (95%CI: 46%-66%), 68% (95%CI: 59%-76%), and 39% (95%CI: 29%-49%) larger kidneys, liver, and pancreas, respectively. We also find a significant linear relationship between the increase in organ volume and the increase in cancer risk (P-value<10−12). These results provide a mechanism explaining why obese individuals have higher cancer risk in several organs: the larger the organ volume the more cells at risk of becoming cancerous. These findings are important for a better understanding of the effects that obesity has on cancer risk and, more generally, for the development of better preventive strategies to limit the mortality caused by obesity.

Autopsy in the 21st Century, 2018

The time has come to stop reexamining the past of the autopsy, cease ruminating on former glories... more The time has come to stop reexamining the past of the autopsy, cease ruminating on former glories, and look ahead to what hospital autopsy can become. Autopsy can remain a method for discovery of new disease entities, demonstrate its value in an increasingly outcome-based medical system, and become an essential part of cutting-edge molecular research. For these developments to take place, autopsy pathology as a field must grow to encompass measures such as prompt and electronically searchable synoptic reporting, standardized practice methods and teaching, and harnessing of centralized resources at regional centers. Autopsy practitioners must seek out and embrace new roles in informing public policy, assessing patient safety, and engaging in clinical trials. The editors hope this book imparts the best available knowledge, helps improve skills, and provides inspiration needed for the autopsy to reassert its vital presence in the heart of medicine, for the twenty-first century and beyond. The fate of this invaluable asset to clinical care, education, public policy, and research is up to all of us.

Table S14. Gene ontology analysis. (XLSX 62 kb)

Table S1. Treatment schedule for PDX models. Table S2. Patient history of PDX eRMS models. Table ... more Table S1. Treatment schedule for PDX models. Table S2. Patient history of PDX eRMS models. Table S3. Statistical summary for CTG-1213/POS-13212. Table S4. Statistical summary for CTG1116/POS-13166. Table S5. Statistical summary for CTG-1628/POS-132166B. Table S6. Statistical summary for J0103366/CF-13A. Table S7. Histological markers of differentiation in PDX eRMS (CTG-1213) mice. Table S8. Patient history of PDX pleoRMS models. Table S9. Statistical summary for CTG-1213/POS-13212. Table S10. Statistical summary for CTG1116/POS-13166. Table S11. Statistical summary for CTG-1628/POS-132166B. Table S12. Histological markers of differentiation in PDX pleoRMS (CTG-800) mice. Table S13. Primers for RT-PCR. (DOCX 41 kb)

Figure S5. Representative immunohistochemistry for CD68 of mouse eRMS tissue and primary cells. N... more Figure S5. Representative immunohistochemistry for CD68 of mouse eRMS tissue and primary cells. Necrotic tissue (a) showed few macrophages present, while viable tumor (b) showed a collection of many macrophages. Macrophage presence was observed as being the same for all treatment groups. (TIF 2929 kb)

Figure S4. siRNA-mediated knockdown of HDAC3 in eRMS and aRMS. Analysis of MHC expression in RD, ... more Figure S4. siRNA-mediated knockdown of HDAC3 in eRMS and aRMS. Analysis of MHC expression in RD, Rh30 and HSMM cell lines transfected with siRNA at 100â nM for 72â h, targeting HDAC3. (TIF 510 kb)