To the Editor: A 74-year-old man presented to the emergency department with sudden-onset sharp pleuritic central chest discomfort radiating to his left shoulder that resolved spontaneously on admission to hospital. He had complained of similar intermittent chest discomfort occurring at rest over 6 weeks with associated breathlessness and poor exercise tolerance. Initial investigations revealed high white cell count (13 × 109/L; normal 4–11 × 109/L), high C-reactive protein (188 mg/L; normal 0–6 mg/L), moderately high corrected calcium (2.77 mmol/L; normal 2.1–2.5 mmol/L), high troponin-I (0.75 μg/L; normal 0–0.1 μg/L) and a normal electrocardiogram. There was also left lower lobe opacification on chest radiograph. He was treated for acute coronary syndrome in view of his history and high cardiac enzymes. Past medical history included total penectomy, perineal urethrostomy, and bilateral groin dissection for penile squamous cell carcinoma (SCC) 18 months before this admission. His annual follow-up computed tomography (CT) did not reveal any metastases. A CT pulmonary angiography (CTPA) was performed on admission because the possibility of the presence of pulmonary emboli was raised. The CTPA (Figure 1) and subsequent abdominal CT showed a solitary splenic tumor invading the left hemidiaphragm and the pericardial sac. A splenic biopsy and immunohistochemistry confirmed it to be metastatic SCC. Subsequent other relevant investigations included a bone scan, which excluded bony metastases, and a low parathyroid hormone (PTH) level (0.64 pmol/L; normal 1.48–7.63 pmol/L). It was not possible to measure PTH-related peptide (PTHrP) levels. Computed tomography images (anterior-posterior lateral views) show a sizable mass invading the left hemidiaphragm and pericardial sac, with a small pleural effusion. Moderate hypercalcemia was treated aggressively with intravenous fluids to marginal effect and required intravenous pamidronate. The case was discussed extensively with surgical and oncology colleagues, but their general consensus in view of his premorbid performance status was to manage the aggressive splenic metastasis conservatively. The patient was discharged to the care of community palliative care colleagues. The authors have not found any previous published cases of metastatic penile SCC presenting as a solitary splenic metastasis invading through the left hemidiaphragm and the pericardial sac. This case highlights the importance of careful evaluation of older adults presenting with a typical history of angina-like chest discomfort but a resultant unusual diagnosis. Physiological changes of aging and multiple comorbid diseases often complicate and obscure the presentation of older adults to the hospital.1 Penile cancers are rare in developed countries but can account for up to 10% of male cancers in developing regions. In the United Kingdom, the reported incidence is 0.6 cases per 100,000 per year.2 The prevalence increases with age after the age of 60 and reaches a peak incidence at the age of 70, with rates probably differing as a result of religious practices and socioeconomic status.3 Risk factors include poor penile hygiene, penile inflammation, phimosis, and number of sexual partners; almost half of patients have had previous exposure to the human papilloma virus.4 Splenic metastasis is a rare complication, arising in fewer than 1% of all metastases, and is associated with a poor prognosis.5,6 SCC accounts for 95% of all penile carcinomas and is a malignant tumor of keratinocytes. Keratinocytes secrete PTHrP, inducing bone osteoclastic resorption, and PTHrP is associated with hypercalcemia as a paraneoplastic complication.7 Hypercalcemia and leukocytosis have reported associations with penile SCC and, in one case report, both resolved after surgery.8 Although the current patient had leukocytosis, the association cannot be definitively determined because there was significant necrotic tissue in the splenic metastasis that could have contributed to leukocytosis. Hypercalcemia in older adults must always prompt urgent evaluation because age-related renal changes lead to fluid loss and may be a manifestation of malignancy as bony metastases or humoral hypercalcemia of malignancy.9 It may present in up to 30% of people with penile cancer with lymphadenopathy.10 The moderately high hypercalcemia was probably a result of the presence of PTHrP because it shares the same N-terminal binding to the type 1 PTH receptor in the body as PTH, increasing bone osteoclastic activity and renal distal tubular calcium reabsorption. Bisphosphonates have been the main treatment for PTHrP-induced hypercalcemia because they inhibit osteoclast formation and their function. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Melvin P.W. Chua and Joel Chin were responsible for the conception of the letter and jointly wrote the first draft. Chinga Chileshe and Surabhi Singh contributed significantly to subsequent critical revisions of the article. All authors were involved in the final approval of version submitted for publication. Sponsor's Role: The authors report no financial conflicts of interest with this article.
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Oct 15, 2024
Rehab Ahmed Rifaai + 3
Open Access