|Year : 2012 | Volume
| Issue : 2 | Page : 308-310
A rare case of metastatic ductal type prostate adenocarcinoma presenting with syndrome of inappropriate secretion of antidiuretic hormone: A case report and review
Hamid Shaaban, David Thomas, Gunwant Guron
Department of Hematology and Oncology, St Michael's Medical Center, Newark, NJ 07102, USA
|Date of Web Publication||26-Jul-2012|
Department of Hematology and Oncology, St Michael's Medical Center, 111 Central Avenue, Newark, NJ 07102
Source of Support: None, Conflict of Interest: None
Ductal adenocarcinoma of the prostate is a rare malignancy and it accounts for less than 1% of prostatic adenocarcinomas as a predominant pattern. In general, the prognosis for these patients is worse than those with typical adenocarcinoma of the prostate. SIADH is a rare paraneoplastic syndrome associated with classic and poorly differentiated acinar prostate adenocarcinoma. To our knowledge, this is the first case of paraneoplastic SIADH associated with ductal type prostate adenocarcinoma. The case highlights once again that the patients with metastatic prostate cancer who present with hyponatremia should get a diagnostic workup for SIADH done due to the potential fatal consequences of this paraneoplastic syndrome.
Keywords: Metastatic ductal type prostate cancer, syndrome of inappropriate secretion of antidiuretic hormone, prostate cancer
|How to cite this article:|
Shaaban H, Thomas D, Guron G. A rare case of metastatic ductal type prostate adenocarcinoma presenting with syndrome of inappropriate secretion of antidiuretic hormone: A case report and review. J Can Res Ther 2012;8:308-10
|How to cite this URL:|
Shaaban H, Thomas D, Guron G. A rare case of metastatic ductal type prostate adenocarcinoma presenting with syndrome of inappropriate secretion of antidiuretic hormone: A case report and review. J Can Res Ther [serial online] 2012 [cited 2020 Jun 4];8:308-10. Available from: http://www.cancerjournal.net/text.asp?2012/8/2/308/98999
| > Introduction|| |
Ductal carcinoma of the prostate is a rare variant of prostate cancer and there is very little in the medical literature that exists on the natural history of this particular histological subtype. It was originally identified by Melicow and Pachter in 1967 and it was thought initially to be a neoplastic proliferation of remnant paramesonephric tissue and at that time it was given the name endometrioid carcinoma. 
Inappropriate secretion of antidiuretic hormone (ADH) is frequently observed in the tumors with ectopic hormone production and is manifested by (i) the syndrome of inappropriate secretion of ADH (SIADH) as a clinical symptom of hormone oversecretion (and improvement of the symptom after tumor excision); (ii) an increase in the serum ADH level and (iii) proof of ADH activity in the tumor tissue.  The class tumor which represents 90% of these are oat cell carcinoma or undifferentiated carcinoma of the lung. We report a case of a patient with ductal prostate adenocarcinoma that initially presented with SIADH. This is to our knowledge the first reported case in the medical literature.
| > Case Report|| |
An 86-year-old male with a past medical history of hypertension and diabetes mellitus presented to our medical institution with altered mental status.
His PSA was 130 ng/ml and sodium was 120 meq/l. He was clinically euvolemic and there was no evidence of psychogenic polydypsia. Additional laboratory tests including serum glucose, creatinine, albumin, triglycerides, thyroid-stimulating hormone and free T4 and prolactin were all within normal limits. Serum cortisol levels were normal and demonstrated appropriate stimulation after cosyntropin infusion. The laboratory tests demonstrated that the serum osmolarity and urinary osmolarity were 258 mOsm/kgH2O and 410 mOsm/kgH2O, respectively. The serum ADH level was 8 pg/ml (normal 1-3).
MRI of brain was normal. CT scan revealed a right hip mass eroding into the acetabulum and an enlarged prostate gland. His bone scan revealed diffuse metastases in the ribs, bilateral femurs and vertebrae.
He subsequently underwent a CT-guided biopsy of the mass, which morphologically revealed metastatic prostate adenocarcinoma. PSA stain on the specimen was negative. He had a trans-urethral resection of the prostate and pathology revealed a poorly differentiated ductal type prostate adenocarcinoma, Gleason score 4+4=8 [Figure 1] and [Figure 2] and this time the PSA stain was positive [Figure 3] and [Figure 4].
|Figure 1: Pathology of prostate biopsy, H&E stain of ductal type prostate adenocarcinoma (×400)|
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|Figure 2: Prostate biopsy histopathology, H&E stain of ductal type prostate adenocarcinoma (×400)|
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|Figure 3: Prostate biopsy showing evidence of positive PSA stain, with staining for androgen receptors (×400)|
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|Figure 4: PSA staining on prostate biopsy specimen, with staining for androgen receptors (×400)|
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He received hypertonic saline (3% sodium chloride, intravenously) and was concomitantly started on complete androgen deprivation therapy (CAD) with an oral dose of Casodex daily along with intramuscular Lupron (LH-RH agonist). He also received intravenous bisphosphonates in light of the extensive bone metastases. His sodium level improved to 138 meq/l. He also became more alert and awake. Over the next 4 weeks, he also received palliative radiation therapy to his right hip. PSA level decreased to 102 ng/ml. Two months later, his PSA decreased to as low as 8.21 ng/ml but then it started to increase to 18 ng/ml after 3 months, and continued to increase up to 36 ng/ml. The prostate cancer was hormone resistant and he needed palliative chemotherapy. However, his performance status continued to deteriorate and he expired soon after. Autopsy revealed high concentration of ADH in the prostate.
| > Discussion|| |
This ductal type of prostate adenocarcinoma accounts for less than 1% of prostatic adenocarcinomas. The incidence of ductal adenocarcinoma, including both pure ductal and mixed ductal-acinar adenocarcinomas, is 3.2% of all prostatic carcinomas.  Immunohistochemistry studies have shown that this rare form of prostate cancer arises from the prostatic ducts themselves. Typical biopsy findings include a number of different architectural patterns including the papillary, cribriform, solid and glandular structures, although many of these can coexist within the same biopsy specimen.  Ductal carcinoma of the prostate usually has Gleason scores of 8 (4+4) or higher, due to the morphology and the more aggressive behavior of the tumor. Prostate ductal carcinoma usually metastasizes to the penis, testis, bone, liver, lungs and brain and it can be difficult to manage in light of its aggressive behavior.  Biopsies from metastatic sites can appear identical, similar or quite different on histological examination from a morphologic perspective, when compared to the primary tumor. 
There are no guidelines and methods on how to manage and treat this rare disease, and current treatment is inferred based upon the management of metastatic prostate adenocarcinoma of any histological subtype. Most patients with metastatic disease will initially receive CAD, which can be achieved either by bilateral orchiectomy or via a GnRH agonist with an anti-androgen compound. When the ductal prostate adenocarcinoma becomes hormone refractory, the patient can be palliated with docetaxel. 
What makes this case even more fascinating is that our patient presented with SIADH. Although rare, SIADH arising from prostate adenocarcinoma has been reported in 14 cases but none of them were reported in this rare histological ductal subtype.
Classic SIADH usually presents with hyponatremia; low serum osmolarity, persistent urinary sodium excretion; euvolemia; normal renal function; and normal thyroid and adrenal function.  The diagnosis is often one of exclusion, with other causes of hyponatremia such as renal disease, liver and cardiac failure, psychogenic polydysia and medications to be considered. Initial management includes fluid restriction or intravenous hypertonic saline depending on severity.
The majority of the reported cases presented at an advanced stage of poorly differentiated adenocarcinoma of the prostate. In addition, the prognosis of SIADH associated with prostate cancer is very poor with a median survival of one year. Almost all of these cases had histology of a mix of moderate to poorly differentiated adenocarcinomas.  Undifferentiated small cell carcinoma was identified in several cases. The exact mechanism of ectopic hormonal production is still not very clear and it has been hypothesized that genetic abnormalities of hormone and/or pro-hormone in tumor cells might cause inappropriate secretion of the hormones.  Metastatic prostate cancer is the result of an amalgamation of genetic chances and hence poorly differentiated cases are more likely to be associated with paraneoplastic ectopic hormone production.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]