Pamela D Unger

Lenox Hill Hospital, New York, New York, United States

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Publications (70)191.56 Total impact

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    ABSTRACT: PLZF is a transcription repressor, which plays a critical role in development, spermatogenesis and oncogenesis. Down-regulation of PLZF has been found in various tumor cell lines. There has been virtually no tissue study on the expression of PLZF in prostate cancer (PCa). PCa is a heterogeneous disease, most of which are indolent and non-lethal. Currently there are no biomarkers that distinguish indolent from aggressive PCa; therefore there is an urgent need for such markers to provide clinical decision support. This study aimed to investigate the expression of PLZF by immunohistochemistry in different grade as well as metastatic PCa and to correlate the alteration of PLZF expression with PCa aggressiveness. We studied a total of 83 primary PCa from biopsies, 43 metastatic PCa and 8 paired primary and metastatic PCa from radical prostatectomies with lymph node dissection. Our results demonstrated that PLZF was strongly expressed in almost all (~100%) benign luminal cells (n=77) and low grade (Gleason pattern 3) PCa (n=70) and weak or absent (100%) in basal cells (n=70). Decreased or lost expression of PLZF was evidenced in 26% of high-grade (Gleason 4 and 5) primary PCa (n=70) and 84% metastatic PCa (n=43). The primary high grade PCa in the prostatectomies shared similar PLZF loss/decrease and histomorphology to that of paired parallel lymph node metastases. These data demonstrated that down-regulation of PLZF is an important molecular process for tumor progression and loss of PLZF expression detected by routine immunohistochemistry is a promising and valuable biomarker for PCa aggressiveness and metastasis in the personalized care of PCa.
    PLoS ONE 01/2015; 10(3):e0121318. DOI:10.1371/journal.pone.0121318 · 3.53 Impact Factor
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    ABSTRACT: Histone H1.5 (HH1.5) is a somatic subtype of the Histone H1 family of linker proteins which are located in the nucleus and play a role in stabilizing higher order chromatin structure, gene expression, DNA repair and cell proliferation. Recently, differential immunohistochemical expression of HH1.5 has been found in various neuroendocrine neoplasms. This study aimed to investigate the immunohistochemical expression of HH1.5 in prostatic adenocarcinomas. Sixty-three prostate needle core biopsies, 9 radical prostatectomy specimens and 3 metastatic prostate cancer cases were evaluated. HH1.5 immunohistochemistry revealed strong nuclear reactivity in 68 out of 73 (93%) cases of prostate adenocarcinomas, compared to only 7 out of 75 (9%) cases of benign prostatic glands (P = <0.0001). In all positive benign prostate epithelia HH1.5 was limited to focal and weak reactivity. Similarly, all 23 foci of high grade prostatic intraepithelial neoplasia exhibited focal staining, with the vast majority having only weak nuclear reactivity. Increased HH1.5 reactivity was observed in Gleason patterns 4 and 5 as compared to Gleason pattern 3, 72% and 56%, respectively (P = <0.02). All three metastatic prostate cancer cases showed strong nuclear reactivity. HH1.5 may be a useful diagnostic tool in evaluating prostatic biopsies, particularly with small foci of cancer. Further studies are needed to support these findings and investigate the possible prognostic significance of HH1.5 in prostatic adenocarcinomas.
    Human pathology 10/2014; 45(10). DOI:10.1016/j.humpath.2014.06.015 · 2.81 Impact Factor
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    ABSTRACT: To describe the diagnosis of local failure after prostate brachytherapy (BT) and treatment options when recurrence is present.
    Brachytherapy 09/2014; 14(2). DOI:10.1016/j.brachy.2014.08.046 · 1.99 Impact Factor
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    ABSTRACT: Micropapillary pattern of growth (MPG) of carcinoma is a unique morphologic pattern. It is uncommon but predicative of poor outcome. MPG has not been described in any germ cell tumor, most notably embryonal carcinoma, which may have papillary configuration. In this study, we reviewed 25 primary testicular germ cell tumors (pure or mixed) containing embryonal carcinoma and 2 lymph node metastases with embroynal carcinoma. Five of the 25 primary cases demonstrated MPG. With available clinical information, 3/3 (100%) cases with MPG and 5/12 (42%) cases without MPG showed evidence of metastases. The 2 lymph node metastases contained predominantly MPG. At metastasis, the median tumor size in primary tumors with MPG was significantly smaller than in those without MPG. Reticulum staining was negative in the regions of MPG and positive for other coexisting non-micropapillary growth patterns in all the 6 embryonal carcinomas. In conclusion, we described MPG in embryonal carcinoma. Although limited by the number of cases, our clinicopathological correlation results raised the possible association of the presence of MPG to the high-rate metastasis of embryonal carcinoma, similar to that seen in other carcinomas with MPG. It is therefore of importance to document this variant growth pattern if present in embryonal carcinoma. We also demonstrated that reticulum is a useful negative marker for identification of MPG.
    International Journal of Surgical Pathology 07/2013; 21(6). DOI:10.1177/1066896913494794 · 0.96 Impact Factor
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    ABSTRACT: Objectives: To identify, describe, and investigate the clinical, radiologic, and pathologic features of 8 cases of telangiectatic oncocytoma. Methods: Fifty-three consecutive renal oncocytomas were reviewed for the telangiectatic pathologic features that were subsequently correlated with the demographic, clinical, and radiographic findings. Results: Telangiectatic oncocytoma accounted for 15% of the 53 renal oncocytomas collected in the past 7 years in our institution. On radiology, almost all presented as an enhancing mass and were suspicious for or consistent with a renal malignant tumor. Grossly, the tumors ranged from 2.4 to 6.0 cm (mean, 3.5 cm) and macroscopically were hemorrhagic spongy or multicystic masses without a central stellate scar. Microscopically, they were characterized by variably sized blood-distended spaces (<0.1-mm to 2- to 3-mm blood lakes) lined by typical oncocytoma cells and without evidence of degenerative changes. Conclusions: With its unique radiologic and pathologic presentations in comparison with classic renal oncocytoma, it is important to recognize this new variant of renal oncocytoma.
    American Journal of Clinical Pathology 07/2013; 140(1):103-8. DOI:10.1309/AJCP9HDXYB2WYYJX · 2.88 Impact Factor
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    ABSTRACT: We present a case of a 61-year-old female presenting with a bladder tumor that occurred 7 years after her previous diagnosis of Clark's level III mid-back melanoma. The bladder tumor was submitted to histopathology without accompanying clinical history, and an initial diagnosis of high-grade urothelial carcinoma was rendered based on epithelioid and sarcomatoid appearing pleomorphic histopathology. We present this case to highlight the diagnostic challenge presented by the rare occurrence of metastatic melanoma to the urinary bladder and the potential pitfall of this lesion being diagnosed as high-grade urothelial carcinoma in the presence of limited clinical history.
    International Journal of Surgical Pathology 06/2013; 22(4). DOI:10.1177/1066896913492199 · 0.96 Impact Factor
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    ABSTRACT: Testicular Sertoli cell tumors are rare and usually sporadic and unifocal. The large cell calcifying Sertoli cell tumor variant is known to be associated with Carney and Peutz-Jeghers syndromes and can be bilateral in these patient populations. There has been no documented association of Sertoli cell tumor with familial adenomatous polyposis (FAP) in the literature. The case presented is a bilateral Sertoli cell tumor occurring in a 34-year-old patient with FAP. The tumor had a conventional Sertoli cell tumor morphology, but with different morphology in the left and right sites. Beta-catenin immunostain showed strong nuclear reactivity in the tumor cells but not the nonneoplastic Sertoli cells. The presence of bilaterality as well as overexpression of beta-catenin by this tumor supports an association of the development of Sertoli cell tumor with the patient's FAP syndrome and adenomatous polyposis coli inactivation.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2012; 461(6). DOI:10.1007/s00428-012-1332-x · 2.56 Impact Factor
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    ABSTRACT: Inactivation of the transcription factor/tumor suppressor Krüppel-like factor 6 (KLF6) has been described in prostate cancer (PC). This study investigated the prevalence and significance of KLF6 exon 2 mutations and splice variants (SVs) in different stages of human PC progression. By using laser-capture microdissection and recombinant clone isolation of DNA sequences to enhance sensitivity, base changes were found in 20 (24.7%) of 81 PC tissues versus 1 (4%) of 25 normal prostate tissues (P = 0.02). Of 26 base changes, 54% produced nonsynonymous mutations. Only three mutations had driver characteristics (PCs, 4%; NPs, 0%). By using microdissection of fresh-frozen tissues and recombinant isolation of RNA sequences, SVs were found in 39 (75%) of 52 PCs and in 10 (45%) of 22 NPs (P = 0.01). Sixteen different SVs, including 13 unique SVs, were identified that used cryptic splicing sites and encoded nonfunctional KLF6 proteins. PCs that had survived hormone (androgen)-deprivation therapy (n = 21) had a significantly higher (P < 0.05) incidence, number, and expression level of nonfunctional SVs than either NPs (n = 22) or hormone-naïve PCs (n = 25). Forced expression of nonfunctional SVs conferred a survival advantage of androgen-dependent LNCaP cells under castration-simulated culture conditions. Together, these data suggest that decreased availability of functional KLF6 contributes to clinical PC progression. This decrease arises infrequently by somatic mutation and more commonly by the acquisition of SVs that provide a survival advantage under castrate conditions, enabling resistance to hormone therapy.
    American Journal Of Pathology 07/2012; 181(3):1007-16. DOI:10.1016/j.ajpath.2012.06.008 · 4.60 Impact Factor
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    ABSTRACT: Objective To present a case of pulmonary metastases from adrenocortical carcinoma that were secreting fully functional cortisol resulting in clinical Cushing's syndrome and to compare the steroidogenic enzyme expression in primary and lung.Methods Our patient's medical history, physical examination, laboratory data, imaging studies and histopathologic results were analyzed and summarized in a case report. The original tumor and the pulmonary metastases were then immunohistochemically evaluated for steroidogenic enzymes.Results Initial endocrinological workup revealed hyperandrogenism and ACTH-independent Cushing's due to a 4 cm left adrenal mass. The patient was initially diagnosed with an adrenal adenoma. Four years later, the patient developed recurrent Cushing's syndrome. Repeat MRI showed no adrenal masses. However, chest CT showed multiple bilateral lung nodules and biopsy revealed metastases of adrenal origin. Upon immunohistochemical analysis, side chain cleavage, 17α hydroxylase, 3β hydroxysteroid dehydrogenase, and 21 hydroxylase immunoreactivity were detected in both the original and pulmonary metastatic lesions, with patterns of disorganized steroidogenesis. Dehydroepiandrosterone-sulfotransferase immunoreactivity was detected in the original tumor but not in the lung metastases.Conclusion This case demonstrates some interesting features of ACC that pose challenges to its management, including the difficulties in establishing the pathological diagnosis, the potential for fully functional steroidogenesis even in late metastases, and the plasticity of steroidogenic potential in tumor cells.
    Endocrine Practice 07/2012; 18(6):1-19. DOI:10.4158/EP12018.CR · 2.49 Impact Factor
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    ABSTRACT: The gC1qR (i.e., gC1q receptor, gC1q binding protein, p32, p33) is a multifunctional cellular protein that interacts with components of the complement, kinin, and coagulation cascades and select microbial pathogens. Enhanced gC1qR expression has been reported in adenocarcinomas arising in a variety of organs. The present study compared gC1qR expression in normal, inflammatory, dysplastic, and malignant tissue of epithelial and mesenchymal origin. gC1qR expression was visualized in tissue sections by immunohistochemistry using the 60.11 monoclonal antibody (i.e., IgG(1) mouse monoclonal antibody directed against gC1qR) and the UltraVision LP Detection System. Sections were counterstained with hematoxylin and examined by light microscopy. Strongest gC1qR expression was noted in epithelial tumors of breast, prostate, liver, lung, and colon, as well as in squamous and basal cell carcinoma of the skin. However, increased gC1qR staining was appreciated also in inflammatory and proliferative lesions of the same cell types, as well as in normal continuously dividing cells. In contrast, tumors of mesenchymal origin generally stained weakly, with the exception of osteoblasts, which stained in both benign and malignant tissues. The data suggest that increased gC1qR expression may be a marker of benign and pathologic cell proliferation, particularly in cells of epithelial origin, with potential diagnostic and therapeutic applications.
    Journal of Histochemistry and Cytochemistry 06/2012; 60(6):467-74. DOI:10.1369/0022155412440882 · 2.40 Impact Factor
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    ABSTRACT: Diagnoses of prostatic carcinoma (PC) have increased with widespread screening. While the use of α-methylacyl coA racemase and high molecular weight cytokeratins have aided in distinguishing benign mimics from malignancy, their sensitivity and specificity are limited. We studied 6C4, a monoclonal antibody to glutamate receptor 2, an excitatory amino acid receptor subunit distributed throughout the central nervous system, on benign prostatic epithelium, high-grade prostatic intraepithelial neoplasia, and PC. Ten cases with post-atrophic or adenosis-like prostate glands were also stained with prostatic intraepithelial neoplasia 4, an immunostain cocktail against α-methylacyl coA racemase, p63, and high molecular weight cytokeratin, in parallel with 6C4. Immunoreactivity for 6C4 was graded as negative (0% to 10%), +1 (11%% to 50%), and +2 (>50%). Malignant epithelium was classified by Gleason patterns. Gleason patterns 4 and 5 were subdivided into cribriform or noncribriform type. Its utility in distinguishing postatrophic or adenosis-like glands from prostate cancer, both of which show absence of basal cells on prostatic intraepithelial neoplasia 4 immunostain, was also investigated. Our results revealed a statistically significant difference in staining of benign secretory prostatic epithelium, high-grade prostatic intraepithelial neoplasia, and low Gleason pattern carcinomas. The results also showed 6C4 is a sensitive marker in separating basal cell negative postatrophic or adenosis-like glands from prostate carcinoma. In addition, there was a statistically significant difference between staining of cribriform versus noncribriform Gleason pattern 4 and 5 carcinomas. A limited number of lymph node metastases from cribriform and noncribriform carcinomas were studied, and they stained the same as the primary tumor in the majority of cases. In conclusion, our preliminary data demonstrated potential utility of 6C4 in the pathologic evaluation of PC.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 03/2012; 20(4):344-9. DOI:10.1097/PAI.0b013e31824013ba · 1.63 Impact Factor
  • Guang-Qian Xiao, Jonathan Chow, Pamela D Unger
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    ABSTRACT: Secondary neoplasms of the urinary bladder are uncommon, with metastatic tumors being an even rarer event. The authors studied the clinicopathology of 11 cases of metastatic tumors to bladder, which were collected from their archives between 1995 and 2010. The most common metastases in this series were breast. Some unusual metastases, including several not being previously reported, were also presented, namely, ileal carcinoid tumor, ileal gastrointestinal stromal tumor, ovarian squamous carcinoma, pancreatic gastrinoma, and renal collecting duct carcinoma. Vast majority of these patients (10/11, 91%) were female. Ninety percent of the patients presented with hematuria and/or obstructive urinary symptom as well as bladder lesions in the area of trigone, posterior wall, and/or bladder neck. Seven of the 11 patients had a known history of other metastases besides the bladder. Most of the patients (4/7, 57%) died within 1 year after diagnosis of bladder metastasis. Metastasis must be distinguished from a primary bladder neoplasm. Morphology and clinical correlation supplemented with immunohistochemical study is critical for the correct diagnosis.
    International Journal of Surgical Pathology 12/2011; 20(4):342-8. DOI:10.1177/1066896911428736 · 0.96 Impact Factor
  • Guang-Qian Xiao, Samuel Mccash, Pamela D Unger
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    ABSTRACT: Two cases are presented in which microscopic groups of retroperitoneal paraganglionic cells simulated metastatic seminomatous tumor. Both patients had histories of mixed testicular germ cell tumor with abdominal metastases and had been treated with chemotherapy. Persistent retroperitoneal disease was favored on follow-up imaging studies. Subsequent retroperitoneal lymph node dissection disclosed multifocal epithelioid cell groups with clear/vacuolated cytoplasm in the fibroconnective and adipose tissue, ranging from 1.0 to 3.0 mm in size. These cell groups were initially interpreted as recurrent metastatic seminoma, but were later reinterpreted as paraganglionic cells, which were confirmed by immunohistochemical analysis. The pathologic features for distinguishing paraganglionic cells from metastatic seminoma are discussed. Awareness of the presence of paraganglia and their distinction from metastatic disease is of practical importance in avoiding an overdiagnosis of malignancy and assuring proper patient management.
    International Journal of Surgical Pathology 08/2011; 19(4):534-7. DOI:10.1177/1066896909360802 · 0.96 Impact Factor
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    ABSTRACT: Paraganglia are an uncommon but previously reported finding in the genitourinary system. Recognition of this entity in the prostate is important in distinguishing it from prostatic adenocarcinoma. In this series, 1230 radical prostectomy specimens were examined for the presence of paraganglia, and a total of 57 cases (4.5%) were found to contain paraganglia. The majority of paraganglia were extraprostatic and could easily mimic extension of prostatic adenocarcinoma into extraprostatic tissue. It is important to recognize paraganglia, particularly when they are extraprostatic and could confer a falsely higher tumor stage to the patient. The paraganglia demonstrated characteristic histology, and immunohistochemistry was supportive when enough tissue was available. No association between patient age and frequency of paraganglia was found.
    International Journal of Surgical Pathology 07/2011; 19(6):772-4. DOI:10.1177/1066896911414567 · 0.96 Impact Factor
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    ABSTRACT: Although urothelial metaplasia has been reported in the fallopian tube, urothelium in the seminal vesicle has been rarely reported. We report 2 cases of urothelial epithelium in seminal vesicles from radical prostatectomy specimens. One case involved a 63-year-old patient with pT2c prostatic adenocarcinoma (Gleason pattern 3+4; total score, 7). The other case involved a 60-year-old patient with pT2c prostatic adenocarcinoma (Gleason pattern 4+3; total score, 7; with focal Gleason pattern 5). Representative sections of the left seminal vesicles from both patients demonstrated a portion of urothelial epithelium consisting of 3 to 8 cell layers, which included superficial (umbrella), intermediate, and basal cells. An abrupt transition from the normal single layer of cuboidal cells of seminal vesicle to multilayered urothelium was identified in 1 case, and circumferential urothelium was identified in the other case. No urothelial metaplasia was seen in the prostatic tissue. The histogenesis of urothelial metaplasia in the seminal vesicle is unclear, but it possibly is a reaction to mechanical irritation, inflammation, or infection, as has been proposed for urothelial metaplasia in the fallopian tube and squamous metaplasia of the pelvic peritoneum. Nevertheless, a rare congenital malformation cannot be ruled out as an etiology. Clinical follow-up of patients with urothelial cell metaplasia of the fimbriae suggests that it bears no biologic significance, yielding no instances of carcinoma. However, whether there will be an impact on fertility awaits further study.
    Annals of diagnostic pathology 03/2011; 16(2):145-7. DOI:10.1016/j.anndiagpath.2010.12.007 · 1.11 Impact Factor
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    ABSTRACT: OBJECTIVE • To evaluate a novel technique to lower positive surgical margin rates while preserving as much of the neurovascular bundles as possible during nerve-sparing robotic prostatectomy. MATERIALS AND METHODS • In situ intraoperative frozen section (IFS) was performed during robotic-assisted laparoscopic prostatectomy (RALP) when there was macroscopic concern for a positive margin or residual prostate tissue. • When IFS was positive, additional sections were taken from the same area until the IFS was negative, similar to the procedure of Mohs micrographic surgery. • Positive surgical margin and biochemical recurrence rates were compared between the patients who underwent IFS and those who did not. RESULTS • Of 970 patients consecutively undergoing RALP at a single institution, IFS was performed on 177 (18%). • Eleven patients (6%) had IFS positive for carcinoma, whereas another 25 (14%) had benign prostatic tissue in the IFS specimen. • IFS and non-IFS patients had similar pathological and nerve-sparing characteristics. • The IFS group had significantly lower rates of positive surgical margins, 7% vs 18% (P = 0.001) but similar rates of biochemical recurrence (5%) at a median follow-up of 11 months. CONCLUSIONS • In situ IFS is an effective way of reducing positive margins during RALP. • Twenty percent of patients who underwent IFS, representing 4% of the overall RALP population, had either malignant or benign prostate tissue removed from their prostatic fossa. • Although a reduction of biochemical recurrence was not demonstrated, the follow-up is short and a difference may become apparent as the data mature.
    BJU International 09/2010; 107(6):975-9. DOI:10.1111/j.1464-410X.2010.09595.x · 3.13 Impact Factor
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    ABSTRACT: Undifferentiated carcinoma with osteoclast-like giant cells arising in the urothelium of the bladder or upper urinary tract is an extremely rare entity. The majority of cases found in the renal pelvis and bladder are associated with either an in situ urothelial malignancy or a conventional high-grade urothelial carcinoma. These malignancies tend to behave poorly with a grim prognosis and course. We report two additional cases of undifferentiated carcinoma with osteoclast-like giant cells of the renal pelvis in two patients disease free 42 and 18 months after surgical treatment, respectively.
    Apmis 05/2010; 118(5):407-12. DOI:10.1111/j.1600-0463.2010.02608.x · 1.92 Impact Factor
  • Guang-Qian Xiao, Pamela D Unger
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    ABSTRACT: Compared with that of urinary bladder, urothelial carcinoma of renal pelvis is infrequent and its morphologic features and presentations have seldom been described. Fifty-nine renal pelvic urothelial carcinomas were evaluated in this study. Seventy-eight percent of these were high-grade tumors, of which 39% contained variable amount of divergent morphology. Forty-four percent of the high-grade urothelial carcinomas presented with an advanced tumor stage. Seventy-eight percent of urothelial carcinomas with divergent morphology displayed a tumor stage of pT2 and above, compared with 21% of classical urothelial carcinomas, which presented at stage pT2 and above. In summary, high-grade and unusual morphology as well as advanced tumor stage were the frequent findings in pelvicalyceal urothelial carcinomas. In addition, divergent morphology was correlated with advanced tumor stage. The clinicopathologic features of pelvicalyceal urothelial carcinomas with unusual divergent morphology were particularly emphasized in this study.
    Annals of diagnostic pathology 04/2010; 14(2):74-80. DOI:10.1016/j.anndiagpath.2009.10.009 · 1.11 Impact Factor
  • The Journal of Urology 04/2010; 183(4). DOI:10.1016/j.juro.2010.02.1945 · 3.75 Impact Factor
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    ABSTRACT: Changes in morphologic patterns over a time course following radiation and their corresponding PSA levels were investigated. A total of 60 patients with prostatic adenocarcinoma treated with brachytherapy between 1993 and 2003, who had at least one positive post-radiation biopsy, were evaluated for their morphologic patterns as well as the associated PSA levels. A total of 86 positive post-radiation biopsies were performed. There were 17 patients with more than 1 positive post-radiation biopsy and 43 patients with single positive biopsy. Among the 17 with more than 1 positive biopsy, the morphologic patterns of treatment effect were commonly followed by patterns without treatment effect on subsequent biopsies. The morphology without treatment effect followed by treatment effect was infrequent. Furthermore, over a time course, the later the positive post-radiation biopsy, the much more common the morphologic pattern without treatment effect was observed. Compared to the morphologic pattern with treatment effect, the morphology without treatment effect was associated with a significantly higher PSA level (mean 0.69 versus 2.78 ng/ml, p<0.05). An increase in the Gleason's score in recurrent carcinoma was also noted in 14% of the cases. Multiple factors were likely involved in the variability of the changes in post-radiation morphologic patterns. A new neoplastic process was particularly considered in some of our cases, which may merit clinical attention. The significant difference in PSA levels between carcinomas without treatment effect and those with treatment effect also suggested a post-radiation variation of tumor biology and a potential role of these patterns in monitoring and managing the patients treated with brachytherapy.
    Pathology - Research and Practice 07/2009; 205(12):843-6. DOI:10.1016/j.prp.2009.07.009 · 1.56 Impact Factor

Publication Stats

1k Citations
191.56 Total Impact Points


  • 2014
    • Lenox Hill Hospital
      New York, New York, United States
  • 1993–2014
    • Mount Sinai Medical Center
      New York, New York, United States
  • 1995–2013
    • Icahn School of Medicine at Mount Sinai
      • • Department of Pathology
      • • Department of Radiation Oncology
      Borough of Manhattan, New York, United States
  • 2012
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 1996
    • CUNY Graduate Center
      New York City, New York, United States