Extrapulmonary small cell carcinomas in the bilateral adrenal glands and perivesical space in a patient with prostate cancer
Article information
Extrapulmonary small cell carcinoma (EPSCC) is a rare malignancy originating from neuroendocrine tumors outside the lungs that typically exhibit aggressive biological behavior characterized by rapid growth and early metastasis. Primary EPSCC is extremely rare in patients with metastatic prostatic adenocarcinoma. Clinically, small cell and neuroendocrine prostate cancers are often characterized by extensive metastatic disease involving the visceral organs and soft tissues, concurrent with paradoxically low serum prostate-specific antigen (PSA) levels. This letter (IRB No. 2024-07-005) describes the rare occurrence of EPSCC in a patient with prostatic adenocarcinoma, with subsequent metastases to both the adrenal glands and perivesical space.
Diagnosis of prostate adenocarcinoma: 10 years ago, a 65-year-old man presented with urinary symptoms including frequency, urgency, and nocturia. Laboratory findings revealed a PSA level of 436.3 ng/mL. Prostate biopsy confirmed adenocarcinoma with a Gleason score of 5+5. Imaging studies, including magnetic resonance imaging (MRI), computed tomography (CT), and bone scans, demonstrated multiple lymph node metastases. Androgen deprivation therapy (ADT) was initiated and the patient achieved disease stability for 9 years.
Initial treatment and follow-up: The patient underwent ADT consisting of luteinizing-releasing hormone agonists and anti-androgens. This treatment effectively controlled the disease as evidenced by a significant decline in PSA levels and stable metastatic lesions. Follow-up included PSA monitoring and imaging to assess disease progression.
Discovery of a left adrenal tumor: 9 years after treatment, routine follow-up imaging revealed a mass in the left adrenal gland. Baseline 24-hour urinary metanephrine, cortisol, and adrenocorticotropic hormone levels were within normal limits. Subsequent adrenal CT imaging demonstrated rapid growth of the right adrenal gland, leading to meta-iodobenzyl guanidine (MIBG) single-photon emission CT (SPECT)/CT being performed. 123I-MIBG SPECT/CT confirmed the malignancy, suggestive of a neuroendocrine tumor arising from a transformed prostate cancer (Fig. 1A). Positron emission tomography-CT (PET-CT), abdominal pelvic CT, and chest CT were negative for any malignant lesions, except in the adrenal glands.
(A) Axial single-photon emission computed tomography (SPECT)/computed tomography (CT) demonstrates a 2.3 cm-sized tumor lesion in the left adrenal gland (white arrow). (B) Tumor cells exhibit diffuse synaptophysin positivity. Immunohistochemical staining. Bar, 100 μm. (C) Kiel-67 staining reveals 80% of tumor nuclei as positive. Bar, 100 μm. (D) Axial SPECT/CT shows a 2.1 cm-sized tumor lesion in the right adrenal gland (white arrow). (E) Magnetic resonance imaging demonstrates a tumor mass in the right perivesical area (white arrow). (F) Cystoscopy revealed no intravesical mass but identified an exophytic lesion (white arrow).
Treatment and diagnosis of left adrenal tumor: The patient underwent laparoscopic left adrenalectomy. Histopathological examination revealed small cell carcinoma (SCC), an uncommon malignancy. Immunohistochemical staining revealed positivity for creatine kinase, synaptophysin, cluster of differentiation (CD) 56, and thyroid transcription factor (TTF)-1, whereas it was negative for chromogranin A (Fig. 1B). The Kiel-67 proliferation index was 80% (Fig. 1C). Imaging did not reveal any evidence of metastasis. Based on these findings, the patient was diagnosed with primary EPSCC.
Emergence and treatment of additional tumors: Follow-up CT performed 6 months later revealed the development of new neoplastic lesions in the right adrenal gland and perivesical space. Further evaluation of the right adrenal gland was performed using 123I-MIBG SPECT/CT (Fig. 1D). Additionally, cystoscopy and bladder MRI were performed to assess the perivesical lesions (Fig. 1E). Cystoscopy revealed no intravesical mass but suggested an exophytic lesion originating from an extravesical structure (Fig. 1F). Considering the rapid tumor progression, concurrent radical prostatectomy and adrenalectomy were performed. Prostatectomy was primarily performed to remove the perivesical mass. However, given the patient's underlying prostate cancer, the procedure was also performed to remove it. Histopathological examination confirmed EPSCC in both the right adrenal gland and perivesical tumor. Immunohistochemical analysis of the prostatectomy specimen revealed PSA positivity but was negative for synaptophysin, chromogranin A, and CD56, excluding metastatic prostate cancer.
Systemic therapy and follow-up: chemotherapy and radiotherapy were considered due to the high risk of recurrence. The patient initiated chemotherapy with a standard etoposide and cisplatin regimen for small cell lung carcinoma (SCLC), which was well-tolerated. Salvage radiation therapy targeted the prostate and bed of the previously resected perivesical tumor. Ongoing surveillance using imaging and laboratory studies is being performed to monitor disease recurrence and treatment efficacy. A 2-year follow-up has shown no evidence of disease recurrence in this patient who underwent chemotherapy and radiation therapy.
This letter describes a rare instance of EPSCC that developed bilaterally in the adrenal glands and perivesical space in a patient with prostate cancer. The emergence of this rare advanced prostate cancer highlights the importance of closely monitoring disease progression and the need to consider the potential for additional malignancies.
Prostate cancer predominantly metastasizes to the bones, lymph nodes, and occasionally to distant organs, such as the liver and lungs. However, the development of EPSCC in the adrenal glands and perivesical space is unusual. This is consistent with recent studies suggesting that neuroendocrine differentiation in prostate cancer can lead to unusual patterns of metastasis, as observed with the involvement of the adrenal glands and perivesical space in this case [1]. However, in our patient, neuroendocrine carcinoma was a secondary primary carcinoma rather than a transformation from an existing prostate adenocarcinoma. The transformation of prostate cancer into a neuroendocrine variant, such as SCC, is associated with a more aggressive disease course and unusual metastatic patterns [2]. The occurrence of EPSCC in this patient, although not directly originating from prostate cancer, was clinically significant because of its aggressive nature and poor prognosis. Diagnosing tumors in atypical locations, such as the adrenal glands and perivesical space, poses significant diagnostic challenges. In such cases, advanced imaging modalities like PET-CT and 123I-MIBG SPECT/CT are often required to complement routine imaging and biochemical tests. The findings of this study suggest that PET-CT is a highly effective imaging modality for the comprehensive evaluation of patients with adrenal gland small cell neuroendocrine carcinoma, enabling the accurate assessment of both the primary tumor extent and metastatic disease. Definitive diagnosis requires immunohistochemistry to confirm the neuroendocrine nature of the tumor and differentiate it from other potential primary or metastatic malignancies. Immunohistochemical markers, including CD56, chromogranin, synaptophysin, TTF-1, and CD44, demonstrate superior specificity for SCC, distinguishing it more effectively from adenocarcinoma [3]. The current therapeutic options for EPSCC remain unvalidated. In SCLC, surgical intervention is advised for localized cases and is often accompanied by pre-and postoperative chemotherapy. Conversely, in advanced-stage SCLC, chemotherapy regimens including cisplatin have demonstrated efficacy, with cisplatin combined with etoposide being the conventional treatment protocol [4]. Therefore, a multidisciplinary approach encompassing surgical, medical, and radiation oncology is essential for optimal management of EPSCC. In this patient, although initial ADT controlled prostate cancer, newly developed tumors in the adrenal glands and perivesical space continued to grow despite ongoing treatment. Subsequent management involved aggressive surgical intervention, followed by adjuvant chemotherapy or radiotherapy. The prognosis of patients with EPSCC is generally poor owing to the aggressive nature of the disease [5]. In this study, the treatment approach involved chemotherapy with etoposide and cisplatin, followed by salvage radiation therapy. Although these are standard treatments for SCLC, they were adapted for this extrapulmonary case owing to its rarity and aggressive nature. Considering the poor prognosis and challenges in managing this disease, continuous surveillance is crucial for monitoring disease recurrence and assessing treatment efficacy.
This letter highlights the importance of considering the atypical emergence of prostate cancer, particularly the unexpectedly rare EPSCC. Effective management of EPSCC requires a multifaceted approach that includes surgical, chemotherapeutic, and radiotherapeutic strategies. Ongoing research and detailed case studies are crucial for improving the diagnostic accuracy and therapeutic outcomes of such challenging conditions.
Notes
CONFLICT OF INTEREST
The author reports no conflict of interest.
FUNDING
This work was supported by the 2024 education, research, and student guidance grant funded by the Jeju National University.