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Leptomeningeal Disease as a Rare Complication of Primary Penile Urethral Cancer

Leptomeningeal Disease as a Rare Complication of Primary Penile Urethral Cancer Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 6349456, 4 pages https://doi.org/10.1155/2020/6349456 Case Report Leptomeningeal Disease as a Rare Complication of Primary Penile Urethral Cancer 1,2 1,3 1,4 1,2 Nan Chen , Thomas Wheeler, Michael Coburn, and Aihua Edward Yen Baylor College of Medicine, Houston, TX, USA Department of Hematology and Oncology, Baylor College of Medicine, USA Department of Pathology, Baylor College of Medicine, USA Department of Urology, Baylor College of Medicine, USA Correspondence should be addressed to Nan Chen; nanc@bcm.edu Received 25 January 2020; Accepted 12 March 2020; Published 24 March 2020 Academic Editor: Jose I. Mayordomo Copyright © 2020 Nan Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Primary penile urethral cancer is a rare genitourinary malignancy arising from the epithelial lining of the urethra. Our patient is a 63-year-old male with newly diagnosed penile urethral carcinoma who presented with headache and was found to have leptomeningeal disease on imaging and cerebral spinal fluid analysis. He was treated with systemic and intrathecal chemotherapy with some response and improvement in symptoms. This is the first reported case of leptomeningeal disease as a complication of penile urethral carcinoma. Recognition and prompt treatment are important; however, overall prognosis of this entity remains poor. 1. Introduction 2. Case Presentation Primary PUC is a rare genitourinary malignancy arising from The patient is a 63-year-old African-American man with a the epithelial lining of the urethra [1] and should be differen- past medical history of hypertension, chronic kidney disease tiated from urothelial cancer arising from the bladder as well (grade II), and distal urethral stricture who presented with as squamous carcinoma arising from the penile glans [2]. one year of hematuria during the beginning and end of his Urethral cancer histologically can be adenocarcinoma, squa- urinary stream. A cystoscopy noted a 7 mm ventral urethral mous, or urothelial, and a retrospective study showed that lesion. A partial urethrectomy showed a squamous cell carci- many of these cancers can have squamous and urothelial his- noma of the penile urethra which was uroplakin-negative, tologic features [2]. Approximately one-third of patients, CK5/6-positive, and p16-positive with carcinoma in situ in such as this case, are p16-positive, implicating HPV as a risk other areas (Figure 1). Staging computed tomography of his factor [2]. Up to half of patients will have a history of internal chest, abdomen, and pelvis showed pelvic and retroperito- strictures, and 25% have a history of sexually transmitted dis- neal lymphadenopathy, scattered lytic bone lesions, and soft eases [3]. It is an aggressive malignancy, with a recently pub- tissue infiltration in the left femoral area consistent with lished large case series demonstrating a median overall metastatic disease. The patient was initiated on carboplatin/- survival of 21-49 months from diagnosis [2, 4]. African- paclitaxel and completed 4 cycles complicated by grade 2 American race was associated with increased mortality [4]. anemia and grade 1 peripheral neuropathy. Repeat imaging The most common sites of metastatic disease are the liver showed resolution of lymphadenopathy and stable lytic bone and lungs. This is the first reported case of leptomeningeal lesions. Given prior cytopenias and good response, he was spread in a patient with primary penile urethral cancer. continued with single-agent paclitaxel and then switched to 2 Case Reports in Oncological Medicine (a) (b) (c) (d) Figure 1: Stains of primary urethral tumor seen at 200x magnification. (a) Urethral squamous cell carcinoma hematoxylin and eosin stain. (b) Urethral squamous cell carcinoma with negative uroplakin stain. (c) Urethral squamous cell carcinoma with positive CK5/6 stain. (d) Urethral squamous cell carcinoma with positive p16 stain. (a) (b) Figure 2: Magnetic resonance imaging of the brain showing progression of leptomeningeal disease. (a) Hyperintensity can be seen in L parasagittal sinus in this T2 Flair at time of diagnosis of LMD. (b) Increased hyperintensity in the same region in this T2 Flair taken 4 months after diagnosis of LMD. nab-paclitaxel due to neuropathy. After his first cycle of nab- revealed cerebral spinal fluid (CSF) protein level of 56 mg/dL paclitaxel, the patient reported an intermittent occipital head- and cytology with poorly differentiated metastatic carci- ache associated with double vision which improved when he noma. Systemic imaging did not show any progression of closed one eye. Magnetic resonance imaging (MRI) of his his disease. His course was complicated by seizures for which brain showed a “faintly enhancing FLAIR signal abnormality he was started on levetiracetam. An Ommaya reservoir was in the parasagittal L superior parietal lobule” (Figure 2). Lep- subsequently placed and intrathecal methotrexate was tomeningeal disease was suspected, and MRIs of spine and started twice weekly, corresponding to an improvement in lumbar puncture were pursued. Cervical, thoracic, and lum- headache and vision changes within two weeks. His CSF bar spine imaging was unremarkable, but lumbar puncture was negative for malignant cells after 6 weeks of treatment, Case Reports in Oncological Medicine 3 and he continued on systemic pembrolizumab and weekly in patients with solid organ malignancies not commonly intrathecal methotrexate. While he demonstrated an initial associated with a propensity to cause LMD, especially as clinical response, repeat MRI brain obtained 4 months after novel cancer treatments continue to prolong survival. More diagnosis showed progression of leptomeningeal disease effective treatment for LMD will be needed, as the prognosis (Figure 2). He developed worsening neurological symptoms, for these patients remains poor. Our patient was treated with including headaches and altered mental status, and passed intrathecal chemotherapy and demonstrated symptomatic from his disease. improvement. 3. Discussion Additional Points Leptomeningeal disease is an underdiagnosed complication Clinical Practice Points. (1) Primary penile urethral cancer of numerous solid malignancies, most commonly breast, (PUC) is a rare and aggressive genitourinary malignancy melanoma, and lung in which cancer cells invade the men- arising from the epithelial lining of the urethra associated ingeal lining of the brain parenchyma [5]. A PubMed with poor prognosis. (2) We present the first case report of search found no other cases associating this complication a patient with leptomeningeal disease (LMD) as a complica- with penile urethral carcinoma, and to the best of our tion of penile urethral cancer. The suspicion for this compli- knowledge, this case represents the first such report. cation must be considered even in patients with solid organ Patients with LMD can present with a range of neurological malignancies not commonly associated with a propensity to symptoms ranging from altered mentation to seizures. If cause LMD, especially as novel cancer treatments continue other sites of disease are present, treatment should consist to prolong survival. of both anatomically directed and systemic therapy. A small proportion of patients, similar to ours, will experience LMD Conflicts of Interest despite improvement in overall disease burden. This may be partially due to the fact that systemic therapy does not The authors declare that they have no conflicts of interest. cross the blood-brain barrier, and the CSF becomes a haven for disease outside of the effects of systemic therapy [6]. References This may also underlie the observation that LMD risk rises with longer cancer survival, which will likely occur with [1] I. Aleksic, S. Rais-Bahrami, M. Daugherty, P. K. Agarwal, further improvement in cancer therapeutics [7]. LMD S. Vourganti, and G. Bratslavsky, “Primary urethral carci- carries a very poor prognosis, and studies in the most com- noma: a Surveillance, Epidemiology, and End Results data mon cancer types demonstrate overall survival of less than analysis identifying predictors of cancer-specific survival,” 6 months [8]. Urology Annals, vol. 10, no. 2, article 226081, pp. 170–174, Intrathecal chemotherapy remains the mainstay of treat- ment. Agents which have been used in this context include [2] M. Zhang, A. J. Adeniran, R. Vikram et al., “Carcinoma of the methotrexate, cytarabine, and thiotepa [9]. Ommaya deliv- urethra,” Human Pathology, vol. 72, pp. 35–44, 2018. ery has been shown to have improved overall survival com- [3] S. L. Traboulsi, J. A. Witjes, and W. Kassouf, “Contempo- pared to delivery via lumbar puncture and thus should be rary management of primary distal urethral cancer,” Uro- attempted when feasible [10]. Administration should be logic Clinics of North America, vol. 43, no. 4, pp. 493–503, twice weekly until the CSF cytology becomes negative [5]. [4] W. Sui, A. RoyChoudhury, S. Wenske, G. J. Decastro, J. M. The role of radiation has not been definitively established, McKiernan, and C. B. Anderson, “Outcomes and prognostic with retrospective studies suggesting it does not provide a factors of primary urethral cancer,” Urology, vol. 100, survival benefit; however, it may be useful in patients with pp. 180–186, 2017. concomitant brain metastases or discrete, symptomatic [5] N. Wang, M. S. Bertalan, and P. K. Brastianos, “Leptomenin- lesions [7, 11]. Expert opinion currently favors a combina- geal metastasis from systemic cancer: review and update on tion approach with intrathecal and systemic chemotherapy management,” Cancer, vol. 124, no. 1, pp. 21–35, 2018. and radiation in certain cases [11]. With prompt recognition, [6] T. Alicia, F. Enrico, and B. Alba, “Chemotherapy in breast can- patients can have improvement of symptoms and quality of cer patients with brain metastases: have new chemotherapic life. Supportive care including steroids and antiepileptic agents changed the clinical outcome?,” Critical Reviews in drugs when needed should be considered in all patients with Oncology/Hematology, vol. 68, no. 3, pp. 212–221, 2008. LMD. While our patient had initial symptomatic improve- [7] M. D. Groves, “New strategies in the management of leptome- ment with IT chemotherapy, his headaches returned within ningeal metastases,” Archives of Neurology, vol. 67, no. 3, a few months, and imaging confirmed progression of lepto- pp. 305–312, 2010. meningeal disease. [8] E. Le Rhun, M. Preusser, M. van den Bent, N. Andratschke, and M. Weller, “How we treat patients with leptomeningeal metastases,” ESMO Open, vol. 4, article e000507, Supplement 4. Conclusion 2, 2019. We present the first reported case of leptomeningeal metasta- [9] F. Mack, B. G. Baumert, N. Schäfer et al., “Therapy of leptome- sis from primary penile urethral carcinoma. Going forward, ningeal metastasis in solid tumors,” Cancer Treatment the suspicion for this complication must be considered even Reviews, vol. 43, pp. 83–91, 2016. 4 Case Reports in Oncological Medicine [10] M. M. de Oca Delgado, B. C. Díaz, J. S. Zambrano et al., “The comparative treatment of intraventricular chemotherapy by Ommaya reservoir vs. lumbar puncture in patients with lepto- meningeal carcinomatosis,” Frontiers in Oncology, vol. 8, p. 509, 2018. [11] E. Le Rhun, M. Weller, D. Brandsma et al., “EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours,” Annals of Oncology, vol. 28, pp. iv84–iv99, http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Leptomeningeal Disease as a Rare Complication of Primary Penile Urethral Cancer

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Copyright © 2020 Nan Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract

Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 6349456, 4 pages https://doi.org/10.1155/2020/6349456 Case Report Leptomeningeal Disease as a Rare Complication of Primary Penile Urethral Cancer 1,2 1,3 1,4 1,2 Nan Chen , Thomas Wheeler, Michael Coburn, and Aihua Edward Yen Baylor College of Medicine, Houston, TX, USA Department of Hematology and Oncology, Baylor College of Medicine, USA Department of Pathology, Baylor College of Medicine, USA Department of Urology, Baylor College of Medicine, USA Correspondence should be addressed to Nan Chen; nanc@bcm.edu Received 25 January 2020; Accepted 12 March 2020; Published 24 March 2020 Academic Editor: Jose I. Mayordomo Copyright © 2020 Nan Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Primary penile urethral cancer is a rare genitourinary malignancy arising from the epithelial lining of the urethra. Our patient is a 63-year-old male with newly diagnosed penile urethral carcinoma who presented with headache and was found to have leptomeningeal disease on imaging and cerebral spinal fluid analysis. He was treated with systemic and intrathecal chemotherapy with some response and improvement in symptoms. This is the first reported case of leptomeningeal disease as a complication of penile urethral carcinoma. Recognition and prompt treatment are important; however, overall prognosis of this entity remains poor. 1. Introduction 2. Case Presentation Primary PUC is a rare genitourinary malignancy arising from The patient is a 63-year-old African-American man with a the epithelial lining of the urethra [1] and should be differen- past medical history of hypertension, chronic kidney disease tiated from urothelial cancer arising from the bladder as well (grade II), and distal urethral stricture who presented with as squamous carcinoma arising from the penile glans [2]. one year of hematuria during the beginning and end of his Urethral cancer histologically can be adenocarcinoma, squa- urinary stream. A cystoscopy noted a 7 mm ventral urethral mous, or urothelial, and a retrospective study showed that lesion. A partial urethrectomy showed a squamous cell carci- many of these cancers can have squamous and urothelial his- noma of the penile urethra which was uroplakin-negative, tologic features [2]. Approximately one-third of patients, CK5/6-positive, and p16-positive with carcinoma in situ in such as this case, are p16-positive, implicating HPV as a risk other areas (Figure 1). Staging computed tomography of his factor [2]. Up to half of patients will have a history of internal chest, abdomen, and pelvis showed pelvic and retroperito- strictures, and 25% have a history of sexually transmitted dis- neal lymphadenopathy, scattered lytic bone lesions, and soft eases [3]. It is an aggressive malignancy, with a recently pub- tissue infiltration in the left femoral area consistent with lished large case series demonstrating a median overall metastatic disease. The patient was initiated on carboplatin/- survival of 21-49 months from diagnosis [2, 4]. African- paclitaxel and completed 4 cycles complicated by grade 2 American race was associated with increased mortality [4]. anemia and grade 1 peripheral neuropathy. Repeat imaging The most common sites of metastatic disease are the liver showed resolution of lymphadenopathy and stable lytic bone and lungs. This is the first reported case of leptomeningeal lesions. Given prior cytopenias and good response, he was spread in a patient with primary penile urethral cancer. continued with single-agent paclitaxel and then switched to 2 Case Reports in Oncological Medicine (a) (b) (c) (d) Figure 1: Stains of primary urethral tumor seen at 200x magnification. (a) Urethral squamous cell carcinoma hematoxylin and eosin stain. (b) Urethral squamous cell carcinoma with negative uroplakin stain. (c) Urethral squamous cell carcinoma with positive CK5/6 stain. (d) Urethral squamous cell carcinoma with positive p16 stain. (a) (b) Figure 2: Magnetic resonance imaging of the brain showing progression of leptomeningeal disease. (a) Hyperintensity can be seen in L parasagittal sinus in this T2 Flair at time of diagnosis of LMD. (b) Increased hyperintensity in the same region in this T2 Flair taken 4 months after diagnosis of LMD. nab-paclitaxel due to neuropathy. After his first cycle of nab- revealed cerebral spinal fluid (CSF) protein level of 56 mg/dL paclitaxel, the patient reported an intermittent occipital head- and cytology with poorly differentiated metastatic carci- ache associated with double vision which improved when he noma. Systemic imaging did not show any progression of closed one eye. Magnetic resonance imaging (MRI) of his his disease. His course was complicated by seizures for which brain showed a “faintly enhancing FLAIR signal abnormality he was started on levetiracetam. An Ommaya reservoir was in the parasagittal L superior parietal lobule” (Figure 2). Lep- subsequently placed and intrathecal methotrexate was tomeningeal disease was suspected, and MRIs of spine and started twice weekly, corresponding to an improvement in lumbar puncture were pursued. Cervical, thoracic, and lum- headache and vision changes within two weeks. His CSF bar spine imaging was unremarkable, but lumbar puncture was negative for malignant cells after 6 weeks of treatment, Case Reports in Oncological Medicine 3 and he continued on systemic pembrolizumab and weekly in patients with solid organ malignancies not commonly intrathecal methotrexate. While he demonstrated an initial associated with a propensity to cause LMD, especially as clinical response, repeat MRI brain obtained 4 months after novel cancer treatments continue to prolong survival. More diagnosis showed progression of leptomeningeal disease effective treatment for LMD will be needed, as the prognosis (Figure 2). He developed worsening neurological symptoms, for these patients remains poor. Our patient was treated with including headaches and altered mental status, and passed intrathecal chemotherapy and demonstrated symptomatic from his disease. improvement. 3. Discussion Additional Points Leptomeningeal disease is an underdiagnosed complication Clinical Practice Points. (1) Primary penile urethral cancer of numerous solid malignancies, most commonly breast, (PUC) is a rare and aggressive genitourinary malignancy melanoma, and lung in which cancer cells invade the men- arising from the epithelial lining of the urethra associated ingeal lining of the brain parenchyma [5]. A PubMed with poor prognosis. (2) We present the first case report of search found no other cases associating this complication a patient with leptomeningeal disease (LMD) as a complica- with penile urethral carcinoma, and to the best of our tion of penile urethral cancer. The suspicion for this compli- knowledge, this case represents the first such report. cation must be considered even in patients with solid organ Patients with LMD can present with a range of neurological malignancies not commonly associated with a propensity to symptoms ranging from altered mentation to seizures. If cause LMD, especially as novel cancer treatments continue other sites of disease are present, treatment should consist to prolong survival. of both anatomically directed and systemic therapy. A small proportion of patients, similar to ours, will experience LMD Conflicts of Interest despite improvement in overall disease burden. This may be partially due to the fact that systemic therapy does not The authors declare that they have no conflicts of interest. cross the blood-brain barrier, and the CSF becomes a haven for disease outside of the effects of systemic therapy [6]. References This may also underlie the observation that LMD risk rises with longer cancer survival, which will likely occur with [1] I. Aleksic, S. Rais-Bahrami, M. Daugherty, P. K. Agarwal, further improvement in cancer therapeutics [7]. LMD S. Vourganti, and G. Bratslavsky, “Primary urethral carci- carries a very poor prognosis, and studies in the most com- noma: a Surveillance, Epidemiology, and End Results data mon cancer types demonstrate overall survival of less than analysis identifying predictors of cancer-specific survival,” 6 months [8]. Urology Annals, vol. 10, no. 2, article 226081, pp. 170–174, Intrathecal chemotherapy remains the mainstay of treat- ment. Agents which have been used in this context include [2] M. Zhang, A. J. Adeniran, R. Vikram et al., “Carcinoma of the methotrexate, cytarabine, and thiotepa [9]. Ommaya deliv- urethra,” Human Pathology, vol. 72, pp. 35–44, 2018. ery has been shown to have improved overall survival com- [3] S. L. Traboulsi, J. A. Witjes, and W. Kassouf, “Contempo- pared to delivery via lumbar puncture and thus should be rary management of primary distal urethral cancer,” Uro- attempted when feasible [10]. Administration should be logic Clinics of North America, vol. 43, no. 4, pp. 493–503, twice weekly until the CSF cytology becomes negative [5]. [4] W. Sui, A. RoyChoudhury, S. Wenske, G. J. Decastro, J. M. The role of radiation has not been definitively established, McKiernan, and C. B. Anderson, “Outcomes and prognostic with retrospective studies suggesting it does not provide a factors of primary urethral cancer,” Urology, vol. 100, survival benefit; however, it may be useful in patients with pp. 180–186, 2017. concomitant brain metastases or discrete, symptomatic [5] N. Wang, M. S. Bertalan, and P. K. Brastianos, “Leptomenin- lesions [7, 11]. Expert opinion currently favors a combina- geal metastasis from systemic cancer: review and update on tion approach with intrathecal and systemic chemotherapy management,” Cancer, vol. 124, no. 1, pp. 21–35, 2018. and radiation in certain cases [11]. With prompt recognition, [6] T. Alicia, F. Enrico, and B. Alba, “Chemotherapy in breast can- patients can have improvement of symptoms and quality of cer patients with brain metastases: have new chemotherapic life. Supportive care including steroids and antiepileptic agents changed the clinical outcome?,” Critical Reviews in drugs when needed should be considered in all patients with Oncology/Hematology, vol. 68, no. 3, pp. 212–221, 2008. LMD. While our patient had initial symptomatic improve- [7] M. D. Groves, “New strategies in the management of leptome- ment with IT chemotherapy, his headaches returned within ningeal metastases,” Archives of Neurology, vol. 67, no. 3, a few months, and imaging confirmed progression of lepto- pp. 305–312, 2010. meningeal disease. [8] E. Le Rhun, M. Preusser, M. van den Bent, N. Andratschke, and M. Weller, “How we treat patients with leptomeningeal metastases,” ESMO Open, vol. 4, article e000507, Supplement 4. Conclusion 2, 2019. We present the first reported case of leptomeningeal metasta- [9] F. Mack, B. G. Baumert, N. Schäfer et al., “Therapy of leptome- sis from primary penile urethral carcinoma. Going forward, ningeal metastasis in solid tumors,” Cancer Treatment the suspicion for this complication must be considered even Reviews, vol. 43, pp. 83–91, 2016. 4 Case Reports in Oncological Medicine [10] M. M. de Oca Delgado, B. C. Díaz, J. S. Zambrano et al., “The comparative treatment of intraventricular chemotherapy by Ommaya reservoir vs. lumbar puncture in patients with lepto- meningeal carcinomatosis,” Frontiers in Oncology, vol. 8, p. 509, 2018. [11] E. Le Rhun, M. Weller, D. Brandsma et al., “EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours,” Annals of Oncology, vol. 28, pp. iv84–iv99,

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Published: Mar 24, 2020

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