Ovarian carcinoma producing parathyroid hormone-related protein causing hypercalcemia and metastatic calcification detected on ¹⁸F-FDG PET-CT

INTRODUCTION

Hypercalcemia is observed in 10-15% of malignant tumor cases and is the most common malignancy-associated endocrine disorder. Tumors causing hypercalcemia are most likely squamous cell carcinomas of the lung, which, together with breast cancer and myeloma, cause the condition in more than 50% of cases and are followed by other squamous cell carcinomas and renal cell carcinoma.[1] Hypercalcemia is known to be associated with about 5% of gynecologic malignant diseases, and cases involving various organs such as the uterus, ovaries, vulva, and vagina have been reported.[2] It is most commonly associated with ovarian cancer, and the majority of cases are clear cell carcinomas and small cell carcinomas.[3] We describe a case of ovarian papillary serous cyst adenocarcinoma with hypercalcemia and metastatic calcification in left rectus abdominis, right rectus abdominis in the region of epigastrium, and pelvic lymph nodes, detected on ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography-computed tomography (PET-CT), presumably resulting from secretion of parathyroid horm one-related protein (PTHrP).

CASE REPORTS

Case 1

A 65-year-old female was diagnosed with carcinoma ovary 10 years ago. Laparoscopic cholecystectomy and ovarian cystectomy was performed in 2004. Histopathology revealed papillary serous cyst adenocarcinoma of ovary with metastatic deposits in serosa of the gallbladder. This was followed by ovarian laparotomy and peritoneal flush. Then, she was followed up with cancer antigen (CA)-125 level. A rising trend in CA-125 level from 250 mg/dl in February 2012 to 1194 mg/dl in November 2012 was noted. She was then referred to our department for ¹⁸F-FDG PET-CT study. ¹⁸F-FDG PET-CT scan revealed FDG-avid irregular soft tissue density mass lesion, measuring 5.1 × 7.7 cm, with calcification in left rectus abdominis (pelvic region). Another FDG-avid soft tissue density mass lesion in the subcutaneous region involving right rectus abdominis muscle, measuring 1.1 × 3.4 cm, in the region of epigastrium was also noted. FDG-avid enlarged lymph nodes with foci of calcification were noted in left inguinal, left external iliac, left obturator, and left common iliac regions [Figure 1]. In view of raised CA-125 levels, these lymph nodes were reported as metastatic lesions. The patient then underwent USG-guided aspiration from the left inguinal lymph node, which was positive for a metastatic lesion. Her serum calcium level was 16 mg/dl (normal 7.4-9.0 mg/dl). PTHrP level was estimated to look for a possible cause of hypercalcemia and was found to be markedly raised at 116 pmol/l (normal 17.6-61.2 pmol/l).

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Figure 1

¹⁸F-FDG PET-CT maximum intensity projection (a) and trans-axial section images revealed FDG-avid mass lesion with calcification in right rectus abdominis muscle (b, c; arrows). Scan also showed FDG-avid metastatic lymph nodes with calcification and increased FDG uptake in left inguinal, left external iliac, left obturator, and in left common iliac regions (d-i)

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Case 2

A 47-year-old female presented with amenorrhea and pain in lower abdomen since 2 months. On pelvic ultrasound examination, lobulated soft tissue lesions showing mildly echogenic center and peripheral hypoechoic soft tissue rim with moderate internal vascularity were noted in the pouch of Douglas [31.7 × 31.9 × 34.0 mm (volume 18 cc)] and left adnexa [32.9 × 24.6 × 17.7 mm (volume 7.5 cc)]. On contrast-enhanced computed tomography (CECT) whole abdomen examination, there were extensive retroperitoneal, retrocrural, and pelvic lymphadenopathies. Majority of the nodes revealed tiny punctuate calcific foci. Both ovaries were bulky and cystic. Her CA-125 level was markedly elevated (4969 mg/dl). A CT-guided fine needle aspiration cytology (FNAC) from retroperitoneal lymph node revealed features of metastatic adenocarcinoma. The patient was advised a trucut biopsy, but biopsy could not be done as the treating gynecologist declined to perform trucut biopsy because of the risk of spread of disease. She was classified as stage IIIC (FIGO staging), as the retroperitoneal lymph nodes were involved with no distant metastasis. She was then referred to our department for ¹⁸F-FDG PET-CT study.¹⁸F-FDG PET-CT scan revealed serosal deposit in the sigmoid colon and pararectal mesentery, with mildly increased FDG uptake and foci of calcification. The scan also revealed multiple enlarged FDG-avid left external iliac, left internal iliac, left common iliac, retroperitoneal, and multiple mesenteric lymph nodes with foci of calcification [Figure 2]. So, a final impression of metastatic disease involving multiple lymph nodes, serosal and mesenteric deposits was reported. The patient later underwent CT-guided FNAC from retroperitoneal lymph node. FNAC smear was found to be cellular with small clusters and cell balls. The cells were found to be crowded with enlarged nuclei with prominent nucleoli in a background of blood, lymphocyte, few mesothelial cells, and adipose tissue fragments [Figure 3]. Her serum calcium level was 15 mg/dl (normal 7.4-9.0 mg/dl). PTHrP level was estimated to look for a possible cause of hypercalcemia and was found to be markedly raised at 108 pmol/l (normal 17.6-61.2 pmol/l).

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Figure 2

¹⁸F-FDG PET-CT maximum intensity projection (a) and trans-axial section images revealed FDG-avid enlarged lymph nodes with calcification in left external iliac (b, c; arrows) and left para-aortic regions (d, e; arrows)

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Figure 3

CT-guided FNAC from retroperitoneal lymph node revealing cellular smear with small clusters and cell balls. The cells are crowded with enlarged nuclei with prominent nucleoli in a background of blood, lymphocyte, few mesothelial cells, and adipose tissue fragments. Features were suggestive of metastatic adenocarcinoma

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DISCUSSION

Hypercalcemia is the most common malignancy-associated endocrine disorder and has been reported to occur in 10-15% of malignant tumor cases.[4] Malignancy-associated hypercalcemia can be basically divided into two subtypes: Local osteolytic hypercalcemia (LOH) caused by local bone erosion and humoral hypercalcemia of malignancy (HHM) by systemic bone loss induced by other causes.[1] The most common cause of HHM is PTHrP produced by tumor cells.[1] Hypercalcemia symptoms include those related to the gastrointestinal tract, such as nausea, vomiting, and constipation; neuropsychiatric symptoms such as depression; and various other symptoms such as dehydration and renal failure. Hypercalcemia is known to be associated with about 5% of gynecologic malignant diseases, and cases involving various organs such as the uterus, ovaries, vulva, and vagina have been reported.[5] It is most commonly associated with ovarian cancer, and the majority of cases are clear cell carcinomas and small cell carcinomas. Although ovarian cancers with hypercalcemia have been reported to have poorer prognoses than those without,[6] there is no clear association between serum calcium levels and prognosis.

Here in our cases, on ¹⁸F-FDG PET-CT imaging, FDG-avid metastatic calcified lesions were demonstrated. Hence, ovarian carcinoma producing PTHrP that causes hypercalcemia and metastatic calcification might be one of the reasons for an FDG-avid calcified lesion detected on ¹⁸F-FDG PET-CT imaging in a case of ovarian carcinoma.