Glomus tumors are rare neoplasms that are usually subungual in location, but can infrequently be found elsewhere in the body. When they occur in extradigital locations, they present a diagnostic ...challenge that may result in delay of definitive management. We report a case of a 51-year-old male who experienced decade long chronic pain because of a glomus tumor in the suprapatellar fat pad of the knee. This case is unique not only because of the glomus tumor’s location, but also because it ultimately required ultrasound-guided needle localization for excision.
18F-Fluciclovine is an amino acid-based radiopharmaceutical used primarily for PET imaging of patients with biochemical recurrence of prostate cancer. We report a case of a 66-year-old man with ...recently diagnosed metastatic castrate-resistant prostate cancer and a left supraclavicular lymph node with incidental radiotracer uptake on 18F-fluciclovine PET/CT. Left neck core needle biopsy confirmed high-grade, poorly differentiated carcinoma with neuroendocrine features positive for synaptophysin and chromogranin, and negative for prostate markers.
Translocation-associated renal cell carcinoma (tRCC) is a rare, aggressive malignancy that primarily affects children and young adults. There is no clear consensus on the most effective treatment for ...tRCC and there are no biomarkers of response to treatments in these patients. We present a case of a 23 year-old female with metastatic tRCC to the lungs who was started on treatment with nivolumab and ipilimumab. She had a complete radiographic response to treatment and has been progression-free for over 18 months. Immunofluorescence imaging performed on the baseline primary tumor sample showed significant intratumoral immune infiltration. Importantly, these cells are present in niches characterized by TCF1+ CD8+ T cells. Histopathologic investigation showed the presence of lymphocytes in the fibrovascular septae and foci of lymphovascular invasion. Furthermore, lymphovascular invasion and intratumor niches with TCF1+ CD8+ T cells may predict a favorable response to treatment with nivolumab and ipilimumab. These findings have significant clinical relevance given that immune checkpoint inhibitors are approved for several malignancies and predictive biomarkers for response to treatment are lacking. Importantly, the identification of these TCF1+ CD8+ T cells may guide treatment for patients with tRCC, which is a rare malignancy without a consensus first-line treatment option.
Cabozantinib (XL-184) is a small molecule inhibitor of the tyrosine kinases c-Met, AXL, and VEGFR2 that has been shown to reduce tumor growth, metastasis, and angiogenesis. After the promising ...results from the METEOR and CABOSUN trials, cabozantinib was approved for use in the first- and second-line setting in patients with advanced RCC. Previously, targeted therapies have been used in the neoadjuvant setting for tumor size reduction and facilitating nephrectomies. The increased response rates with cabozantinib in metastatic renal cell carcinoma (mRCC), along with the other neoadjuvant TKI data, strongly support an expanded role for cabozantinib in the neoadjuvant setting.
We report on a 59-year-old gentleman presenting with an unresectable 21.7 cm left renal cell carcinoma (RCC) with extension to soft tissue and muscles of the thoracic cage, psoas muscle, posterior abdominal wall, tail of pancreas, splenic flexure of colon, and inferior margin of spleen. Presurgical, neoadjuvant systemic therapy with cabozantinib was initiated for 11 months in total. Initially after 2 months of cabozantinib, magnetic resonance imaging (MRI) revealed a significant reduction (44.2%) in tumor diameter from 21.7 to 12.1 cm with decreased extension into adjacent structures. After 11 months total of cabozantinib, the corresponding MRI showed grossly stable size of the tumor and significant resolution of invasion of adjacent structures. After washout of cabozantinib, radical resection, including nephrectomy, was successfully performed without any major complications, either intra-operative or perioperative. Negative margins were achieved.
This is a report of neoadjuvant cabozantinib downsizing a tumor and enabling surgical resection in this patient with locally advanced RCC. Our findings demonstrate that neoadjuvant cabozantinib to facilitate subsequent surgical resection may be a feasible option for patients presenting with unresectable RCC.
Inflammatory pseudotumor or pseudosarcomatous fibromyxoid tumor and postoperative spindle cell nodule of the bladder are unusual lesions of uncertain pathogenesis which share overlapping, if not ...identical, histologic features. We present our experience with 42 cases, the largest series to date, to study the etio-pathogenesis, histologic features, biologic behavior and relationship to "inflammatory myofibroblastic tumor" of childhood. Patients ranged in age from 7 to 77 years (mean 47 y) and males predominated (3.2:1). Most patients presented with hematuria (31/42). Common associations were smoking (10/30) and previous instrumentation or surgery (9/42). The clinicopathologic features of patients having or not having prior instrumentation were identical. Grossly the lesions were polypoid or nodular and involved any portion of bladder wall, most commonly the dome (9/27) and measured 1 to 10 cm (mean 4 cm). They were composed of spindled and stellate cells arranged in a myxoid background with numerous inflammatory cells. Myxoid hypocellular areas were more pronounced near the mucosal surface with greater cellularity and a fascicular arrangement in the deep aspect of the lesion. "Atypical" features included mitotic activity (0 to 20/10 HPF; mean 2/10 HPF; median 1/10 HPF; none atypical), necrosis (22/42), and extension into muscularis propria (28/32) or perivesicular fat (3/8). Lesions were positive for cytokeratin (31/33), SMA (23/34), desmin (21/35), and Alk-1 protein (12/26). FISH confirmed the Alk-1 translocation in 4/6 cases. Treatment included transurethral resection (30/42), partial cystectomy (9/42), and total cystectomy (3/42). Initial diagnostic error resulted in radiotherapy and chemotherapy in 3 patients. Follow-up was available in 28 patients. (range 3 to 93 mo; median 25 mo). Three patients developed recurrences, but none had metastases. Because the clinicopathologic features of lesions associated with and without instrumentation were similar and inseparable, we believe they are essentially the same entity, and propose the term pseudosarcomatous myofibroblastic proliferation. The preponderance of evidence which includes the extravesical growth, local recurrence, and Alk-1 gene translocation in some cases suggests perhaps a neoplastic process with limited growth potential. Even in the face of atypical histologic features (muscle invasion and necrosis) the prognosis is excellent. Despite the Alk-1 gene translocation, there continues to be sufficient evidence for regarding these as distinct from the so-called inflammatory myofibroblastic tumor of childhood.
Urologic pathology is evolving rapidly. Emerging trends include the expanded diagnostic utility of biomarkers and molecular testing, as well as adapting to the plethora of technical advances ...occurring in genitourinary oncology, surgical practice, and imaging. We illustrate those trends by highlighting our approach to the diagnostic workup of a few selected disease entities that pathologists may encounter, including newly recognized subtypes of renal cell carcinoma, pheochromocytoma, and prostate cancer, some of which harbor a distinctive chromosomal translocation, gene loss, or mutation. We illustrate applications of immunohistochemistry for differential diagnosis of needle core renal biopsies, intraductal carcinoma of the prostate, and amyloidosis and cite encouraging results from early studies using targeted gene expression panels to predict recurrence after prostate cancer surgery. At our institution, pathologists are working closely with urologic surgeons and interventional radiologists to explore the use of intraoperative frozen sections for margins and nerve sparing during robotic prostatectomy, to pioneer minimally invasive videoscopic inguinal lymphadenectomy, and to refine image-guided needle core biopsies and cryotherapy of prostate cancer as well as blue-light/fluorescence cystoscopy. This collaborative, multidisciplinary approach enhances clinical management and research, and optimizes the care of patients with urologic disorders.
The role of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma is a subject of debate. We report a durable complete response in a 62-year-old man Jehovah's Witness with ...metastatic clear cell renal cell carcinoma who received two cycles of nivolumab/ipilimumab followed by radical nephrectomy and metastasectomy of known pulmonary disease site, both without a clinical need for perioperative blood transfusions. The patient continues to be without evidence of disease and without additional need for systemic therapy over a year after his radical nephrectomy. The case highlights that cytoreductive nephrectomy continues to play a role in the era of immune checkpoint inhibitors.
Background: Malakoplakia is a rare benign lesion, usually associated with deficient intralysosomal degradation of microorganisms, more commonly, Escherichia coli. Malakoplakia occurs in various organ ...systems, the most frequently affected site being the urinary bladder. We report a rare case of isolated extensive malakoplakia involving the prostate, diagnosed on transurethral resection performed for radiologically suspected prostatic abscesses. Case Presentation: A 61-year-old African American male presented with symptoms of urinary obstruction for the past 2 months. His medical history was significant for immunosuppression (liver transplantation 3 months prior and diabetes mellitus). He reported four episodes of E. coli-associated urinary tract infection after his liver transplantation. Serum prostate specific antigen was 1.83 ng/cc (normal inferior to 4 ng/cc), and urine culture was positive for E. coli sensitive to ceftriaxone. Pelvic magnetic resonance imaging was suggestive of prostatitis with prostatic abscesses; cystoscopy was unremarkable. The patient was started on intravenous ceftriaxone therapy. A standard bipolar transurethral resection of the prostate was performed, and purulent-like material was encountered in the resected tissue. Histologic examination demonstrated extensive infiltration and replacement of the prostatic tissue by sheets of pink histiocytes with targetoid inclusions consistent with Michaelis–Gutmann bodies, ultimately confirming malakoplakia of the prostate. Conclusion: Prostatic malakoplakia is an unexpected diagnosis in patients suspected of having malignancy or prostatitis. Its exact pathogenesis is unknown, but it involves defective bacterial degradation after phagocytosis. E. coli is often cultured from the patients' urine. Immunosuppression, present in our patient, is a well-known associated factor. Prostatic malakoplakia can radiologically masquerade as prostatic adenocarcinoma, despite the use of cutting-edge imaging technology. With the growing use of multiparametric 3T prostate magnetic resonance imaging to screen for prostate cancer, it is possible that urologists, radiologists, and pathologists will encounter prostatic malakoplakia more frequently in the future.
•Non-urothelial bladder cancers are rare and typically excluded from enrollment in prospective clinical trials.•Treatment is often extrapolated from expert opinion and retrospective data.•Squamous ...cell carcinoma, adenocarcinoma, and small cell carcinoma of the bladder are three such non-urothelial tumors that warrant special consideration given divergence in biology and subsequent management compared to urothelial carcinoma.•This review takes a comprehensive look at these three non-urothelial cancers and summarizes the literature on their management in both the localized and metastatic settings as well as future directions and ongoing clinical trial opportunities.
Urothelial carcinoma accounts for approximately 90% of all bladder cancer diagnoses. Localized, muscle-invasive disease is often managed with a multidisciplinary approach including either neoadjuvant chemotherapy (NAC) followed by radical cystectomy or concurrent chemoradiation, whereas multiple immunotherapies and novel antibody drug conjugates have recently joined platinum-based chemotherapy as standard of care therapy for metastatic disease. However, the clinical trials leading to these standards often require majority if not complete urothelial histology for eligibility. As many as one quarter of patients diagnosed with bladder cancer will have either divergent differentiation of their urothelial carcinoma or an alternate epithelial tumor such as squamous cell carcinoma, adenocarcinoma, or small cell carcinoma; even more rare are non-epithelial tumors such as sarcoma. The rarity of these diseases and their general exclusion from treatment within prospective clinical trials has created a challenging situation where treatment plans are often derived from case series or extrapolated from other disease types and outcomes are poor compared to pure urothelial carcinoma. In this review, we summarize the existing data on the diagnosis and treatment of epithelial, non-urothelial bladder cancers including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma in their localized and advances stages. We will also review the current clinical trial landscape investigating novel approaches to these diseases.
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