Surreal illustration of calcium veins in a cracking stone body, representing hypercalcemia and cancer.

Rare Cancer Alert: When Penile Cancer Mimics a Hormone Disorder

Jordan Keane in Health & Wellness December 2025 • 4 min read.

"Unveiling the unexpected link between penile squamous cell carcinoma and parathyroid-related peptide (PTH-rP) secretion: A case study."

Hypercalcemia, characterized by elevated calcium levels in the blood, is a serious condition often linked to cancer. It occurs when cancer cells release substances that disrupt the body's normal calcium balance. This disruption can lead to a range of complications, significantly impacting a patient's prognosis and quality of life. Understanding the causes and mechanisms behind hypercalcemia in cancer is crucial for effective diagnosis and management.

Penile cancer, while relatively rare, presents unique challenges in diagnosis and treatment. Squamous cell carcinoma is the most common type, often linked to factors such as HPV infection and poor hygiene. Early detection is vital, as the disease can progress rapidly if left untreated. Recognizing unusual symptoms and seeking prompt medical attention are key to improving patient outcomes.

A recent case study sheds light on a rare and complex interplay between penile cancer and hypercalcemia. The study details the experience of a 47-year-old man whose penile squamous cell carcinoma led to the ectopic secretion of parathyroid-related peptide (PTH-rP), a hormone-like substance that dramatically elevates calcium levels. This unusual presentation highlights the importance of considering paraneoplastic syndromes in cancer diagnosis.

The Case: Atypical Cancer Presentation

Surreal illustration of calcium veins in a cracking stone body, representing hypercalcemia and cancer.

A 47-year-old man presented to the emergency department with severe lesions in the genital area and groin, accompanied by fever, weight loss, and muscle weakness. Physical examination revealed warty-like lesions with ulceration and purulent material. A biopsy confirmed penile invasive squamous cell carcinoma. Initial lab work showed leukocytosis and a significantly elevated total serum calcium level of 15.1 mg/dL (normal range 8.6-10.2 mg/dL), adjusted to an albumin-corrected calcium level of 16.9 mg/dL.

Further investigation revealed very low levels of parathyroid hormone (PTH) and a markedly elevated level of parathyroid-related peptide (PTH-rP) at 127 pg/mL (normal range 14-27 pg/mL). These findings suggested that the hypercalcemia was caused by the tumor's ectopic secretion of PTH-rP, a phenomenon known as humoral hypercalcemia of malignancy (HHM).

Initial Symptoms: Severe lesions, fever, weight loss, muscle weakness.
Diagnosis: Penile invasive squamous cell carcinoma confirmed by biopsy.
Key Lab Results: High serum calcium, low PTH, elevated PTH-rP.
Treatment Challenges: Extensive injury and infection limited surgical and chemotherapy options.

The patient was initially managed with vigorous hydration and loop diuretics, but these measures were insufficient to control the hypercalcemia. Consequently, a dose of 4 mg zoledronic acid was administered, resulting in a significant improvement. The patient’s calcium levels normalized within four weeks, requiring another dose to maintain normal levels. Imaging studies ruled out distant metastasis but revealed extensive tissue invasion. The tumor's size and infection made surgical resection impossible and the patient was given chemotherapy without success. Due to the infection, a decision was made to focus on palliative care.

Clinical Significance and What to Watch For

This case underscores the importance of considering paraneoplastic syndromes like HHM in patients with cancer. While penile cancer is relatively rare, this case highlights an atypical presentation that can significantly impact patient outcomes. Recognizing the signs and symptoms of hypercalcemia, such as muscle weakness, fatigue, and altered mental status, is crucial for early detection and management. If you or someone you know experiences these symptoms alongside a cancer diagnosis, prompt medical evaluation is essential. Early detection, awareness of paraneoplastic syndromes, and management of hypercalcemia can significantly improve quality of life and treatment outcomes.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1590/0004-2730000002880, Alternate LINK

Title: Rare Association Between Penile Squamous Cell Carcinoma And Parathyroid Related Peptide (Pth-Rp) Secretion

Subject: General Medicine

Journal: Arquivos Brasileiros de Endocrinologia & Metabologia

Publisher: FapUNIFESP (SciELO)

Authors: Rogelio Trejo-Rosales, Maria J. Nevarez-Barragan, Mercedes G. Rosas-Jurado, Ivan Perez-Diaz, Ana Paula Piana Bezaury

Published: 2014-08-01

Everything You Need To Know

What is humoral hypercalcemia of malignancy (HHM), and how is it related to penile squamous cell carcinoma?

Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome where cancer cells secrete substances that disrupt the body's calcium balance, leading to elevated calcium levels in the blood. In the context of penile squamous cell carcinoma, certain tumors can ectopically secrete parathyroid-related peptide (PTH-rP). PTH-rP mimics the action of parathyroid hormone (PTH), increasing calcium levels and causing HHM. This atypical presentation, as seen in a recent case study, highlights the importance of considering HHM in patients with penile cancer, especially when hypercalcemia is present.

What initial symptoms might suggest that penile squamous cell carcinoma is causing hypercalcemia?

Initial symptoms that might suggest hypercalcemia caused by penile squamous cell carcinoma include severe lesions in the genital area and groin, accompanied by fever, weight loss, and muscle weakness. These symptoms, combined with the presence of warty-like lesions with ulceration and purulent material, should prompt further investigation. Key lab results indicating hypercalcemia would include high serum calcium levels, low parathyroid hormone (PTH) levels, and elevated parathyroid-related peptide (PTH-rP) levels.

Why is early detection so crucial for penile squamous cell carcinoma, and what are some of the challenges in its treatment?

Early detection is vital for penile squamous cell carcinoma because the disease can progress rapidly if left untreated. Recognizing unusual symptoms and seeking prompt medical attention are key to improving patient outcomes. Challenges in treatment can arise from extensive tissue invasion and infection, which may limit surgical and chemotherapy options. In cases where the tumor is large and infected, like the one described, palliative care might become the primary focus.

How does parathyroid-related peptide (PTH-rP) contribute to hypercalcemia in cases of penile squamous cell carcinoma?

Parathyroid-related peptide (PTH-rP) contributes to hypercalcemia because it mimics the action of parathyroid hormone (PTH), which is normally responsible for regulating calcium levels in the body. When penile squamous cell carcinoma cells ectopically secrete PTH-rP, it binds to the same receptors as PTH, leading to increased bone resorption, increased renal reabsorption of calcium, and increased production of 1,25-dihydroxyvitamin D, all of which elevate serum calcium levels. This phenomenon is known as humoral hypercalcemia of malignancy (HHM).

What are the clinical implications of recognizing paraneoplastic syndromes like humoral hypercalcemia of malignancy (HHM) in cancer patients, and what specific signs should patients and doctors watch for?

Recognizing paraneoplastic syndromes like humoral hypercalcemia of malignancy (HHM) is clinically significant because it can drastically affect patient outcomes and treatment strategies. Overlooking HHM can lead to severe complications from hypercalcemia, such as muscle weakness, fatigue, altered mental status, and cardiac arrhythmias. Patients and doctors should be vigilant for these signs, especially in the context of a cancer diagnosis. Early detection and management of hypercalcemia, through treatments like vigorous hydration, loop diuretics, and bisphosphonates (e.g., zoledronic acid), can significantly improve the patient's quality of life and overall prognosis. Additionally, identifying HHM may prompt a more thorough investigation for the underlying malignancy and influence treatment decisions.