Cholesterol granuloma forming the solid components within an endometrioma showing intense FDG uptake, mimicking malignancy: A case report

A 68-year-old woman presented to a local gynecologist with a chief complaint of vulvar pruritus. Transvaginal ultrasonography revealed a right ovarian cystic lesion, and she was referred to our hospital for further evaluation. The tumor marker Cancer antigen (CA) 125 was elevated to 40.4 U/mL (normal ≤35 U/mL), while CA 19-9 was 10.8 U/mL and carcinoembryonic antigen (CEA) was within the normal range at <1.8 ng/mL. The patient had a history of hypertension and a phyllodes tumor of the breast at age 45. Menopause occurred at age 51. Cervical cytology revealed negative for intraepithelial lesion or malignancy (NILM). Transvaginal ultrasonography demonstrated a unilocular cyst measuring 59 mm in the right ovary with hypoechoic contents. In addition, a multilocular cyst measuring 23 × 22 mm with heterogeneous internal echoes was recognized in the left ovary. The uterus appeared normal. MRI revealed a unilocular cyst measuring 52 × 51 × 52 mm in the right pelvic cavity, with signal intensity equal to that of water on both T1-weighted images (T1WIs) and T2-weighted images (T2WIs), suggesting a serous cystadenoma ( Fig. 1 A–C: white arrow). The left ovary contained a cyst measuring 46 × 36 × 30 mm, showing slightly higher signal intensity than fat on T1WIs, which was not suppressed on fat-suppressed T1WIs, and low signal intensity on T2WIs suggesting an endometrioma ( Fig. 1 A–C: black arrow). Inside this cyst, a nodular solid component was noted, showing low signal intensity on both T1WIs and T2WIs and partial high signal on diffusion-weighted images and restricted diffusion on an apparent diffusion coefficient (ADC) map (ADC value: 0.61 × 10 −3 mm 2 /s) ( Fig. 1 A–E: arrowhead). FDG-PET/CT demonstrated intense FDG uptake in the solid component (standardized uptake value (SUV) max = 13.0), with no evidence of distant metastasis ( Fig. 2 ). Fig. 1 A unilocular cystic lesion measuring 52 mm is observed in the right ovary (A–C: white arrow). The contents show low signal intensity (SI) on T1-weighted images (T1WIs) (B) and high SI on T1-weighted images (T2WIs) (A), suggesting a serous cystadenoma. A multilocular, lobulated cystic lesion (A–C: black arrow) measuring 48 mm in maximal diameter is observed in the left ovary. The contents show higher SI than fat on T1WIs (B) and are not suppressed on fat-suppressed T1WIs (C). On T2WIs (A), the lesion demonstrates low SI, similar to that of endometriomas. Scattered nodules are present within the lesion (A–E: arrowhead), showing low SI on T2WIs (A) and heterogeneous signal on T1WIs (B). Some of these nodules demonstrate high SI on diffusion-weighted imaging (D) and restricted diffusion on an ADC map (ADC value: 0.61 × 10 −3 mm 2 /s) (E). The uterus is atrophic with no abnormalities noted (not shown). Fig 1 Fig. 2 FDG-PET/CT demonstrates intense FDG uptake in the solid component inside the left ovarian cyst (arrow). (standardized uptake value (SUV) max = 13.0). Fig 2 A unilocular cystic lesion measuring 52 mm is observed in the right ovary (A–C: white arrow). The contents show low signal intensity (SI) on T1-weighted images (T1WIs) (B) and high SI on T1-weighted images (T2WIs) (A), suggesting a serous cystadenoma. A multilocular, lobulated cystic lesion (A–C: black arrow) measuring 48 mm in maximal diameter is observed in the left ovary. The contents show higher SI than fat on T1WIs (B) and are not suppressed on fat-suppressed T1WIs (C). On T2WIs (A), the lesion demonstrates low SI, similar to that of endometriomas. Scattered nodules are present within the lesion (A–E: arrowhead), showing low SI on T2WIs (A) and heterogeneous signal on T1WIs (B). Some of these nodules demonstrate high SI on diffusion-weighted imaging (D) and restricted diffusion on an ADC map (ADC value: 0.61 × 10 −3 mm 2 /s) (E). The uterus is atrophic with no abnormalities noted (not shown). FDG-PET/CT demonstrates intense FDG uptake in the solid component inside the left ovarian cyst (arrow). (standardized uptake value (SUV) max = 13.0). Based on these findings, malignant transformation of the left ovarian endometrioma was suspected, and abdominal simple total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. Intraoperative peritoneal cytology was negative, and frozen-section analysis revealed a lesion containing hemosiderin but no evidence of malignancy. On gross examination of the resected specimen, the solid component within the left ovarian cyst appeared a yellowish-white color and partially dark brown areas ( Fig. 3 ). Histopathologically, on hematoxylin and eosin staining, the cyst wall contained histiocytes that had phagocytosed red blood cells and deposits of hemosiderin, findings consistent with an endometrioma. The solid component within the cyst showed cholesterol crystals surrounded by granulomatous inflammation containing abundant hemosiderin ( Fig. 4 ). Based on these findings, the lesion was diagnosed as an endometrioma with cholesterol granuloma. The right ovarian cyst was diagnosed as a serous cystadenoma. Fig. 3 Macroscopic appearance of the left ovarian cyst shows a solid component within the cyst, with a yellowish-white color (white arrow) and partially dark brown areas (black arrow). Bar = 1cm. Fig 3 Fig. 4 Histopathologically, on hematoxylin and eosin staining, the solid component within the cyst showed cholesterol crystals (white arrow) surrounded by granulomatous inflammation containing abundant hemosiderin (black arrow). Bar = 200µm. Fig 4 Macroscopic appearance of the left ovarian cyst shows a solid component within the cyst, with a yellowish-white color (white arrow) and partially dark brown areas (black arrow). Bar = 1cm. Histopathologically, on hematoxylin and eosin staining, the solid component within the cyst showed cholesterol crystals (white arrow) surrounded by granulomatous inflammation containing abundant hemosiderin (black arrow). Bar = 200µm.

Go Nakai: Writing - original draft; Conceptualization. Hiroki Matsutani: Patient’s data curation. Takashi Yamada: Pathological analysis; Supervision. Tomohito Tanaka: Clinical diagnosis and management of the patient. Kazuhiro Yamamoto: Imaging data curation. Keigo Osuga: Writing - review & editing; Supervision.

Not applicable.

Written informed consent for publication of this case report was obtained from the patient.

Written, informed consent for publication of this case was obtained from the patient.

Ovarian malignant tumors such as endometrioid carcinoma, clear cell carcinoma, and seromucinous borderline tumors are known to arise from endometriosis although it occurs in about 1% of cases [ 1 ]. On magnetic resonance (MR) imaging, the characteristic findings suggesting malignant transformation in endometriomas (ovarian endometriotic cysts) include cyst wall thickening and the presence of solid components or mural nodules with contrast enhancement [ 2 ]. On fluorodeoxyglucose positron emission tomography (FDG-PET), ovarian cancers usually show FDG uptake [ 3 ], however, some endometriomas are known to exhibit false-positive FDG accumulation [ 4 ]. We report a case of an endometrioma forming solid components showing intense FDG uptake, which was suspected to be malignant preoperatively but was pathologically diagnosed as a cholesterol granuloma.

In the diagnosis of ovarian tumors, the presence of a solid component with internal blood flow or FDG uptake within an endometrioma raises suspicion for malignant transformation [ 2 , 3 ]. In contrast, when no internal blood flow is observed within the solid component, it is diagnosed as a blood clot within the endometrioma. In the present case, the former condition applied, and it was difficult to rule out the possibility of malignancy preoperatively. “Cholesterin” refers to cholesterol, and the crystals are called cholesterol crystals. Cholesterol is a component of cell membranes and steroid hormones, and in particular, cholesterol present in atherosclerotic plaques of arterial walls may cause embolism when ruptured. The causes of granulomatous inflammation include infectious agents (bacteria such as Mycobacterium tuberculosis, Treponema pallidum, Mycobacterium leprae , atypical mycobacteria; fungi such as Histoplasma capsulatum and Cryptococcus ; and parasites such as Schistosoma ), foreign materials, and chemical substances, as well as idiopathic conditions such as sarcoidosis and Crohn’s disease. Cholesterol granuloma is classified as an endogenous foreign-body granuloma. Endogenous substances that can cause granulomatous inflammation include uric acid crystals, sequestrated bone (sequestrum), and keratin [ 5 ]. Cholesterol granuloma is most commonly observed in the middle ear. Regarding other organs, cholesterol granuloma has rarely been reported in the breast [ 6 ], testis [ 7 ], liver, spleen [ 8 ], kidney, parotid gland [ 9 ], lymph nodes [ 10 ], thyroglossal duct [ 11 ], rib and peritoneum [ 12 ]. However, cholesterol granuloma in the ovary has never been previously reported as a case report. Although the cause of the granuloma remains unclear, high cholesterol crystal deposition, prior inflammation, or trauma may have been involved. The term “cholesterin” (the obsolete term for cholesterol) is occasionally observed in pathological diagnostic reports of gynecologic tumors. A review of our institution’s pathology database revealed the occurrence of “cholesterin” in necrotic areas of tumors (including post-treatment changes), teratomas, struma ovarii, endometriomas, hemorrhagic ovarian cysts, and mucinous cystadenomas. However, granuloma formation associated with “cholesterin” was not observed. In studies comparing SUVmax for differentiating malignant from benign ovarian tumors, endometriomas have been reported as a major cause of false-positive results. Rieber et al. reported that among 91 benign ovarian tumors, 20 (22%) showed false-positive FDG uptake on PET, the most common being physiological cysts such as follicular or corpus luteum cysts (five cases), followed by endometriomas (four cases). One case of cholesterol granuloma was also included [ 13 ]. Cholesterol granuloma is formed as a result of a foreign body–type granulomatous inflammatory reaction to cholesterol crystals within the tissue and is therefore presumed to show intense FDG uptake. Kusunoki et al. [ 4 ] investigated 1599 consecutive patients diagnosed with endometriomas and found that 31 patients had nodules with contrast enhancement, which raised suspicion for malignant transformation and led to laparotomy. However, histopathological examination revealed that 11 of these 31 cases (35%) were benign. Among them, 7 cases consisted of hemosiderin deposits, endometriomas, or endometrial stroma, while the remaining cases involved other benign tumors. Comparison between the 11 benign and 20 malignant cases demonstrated that malignant cases were significantly older, had larger cysts, lacked T2 shading, and showed higher SUV in the solid components. Nevertheless, there was an overlap in SUV between benign and malignant lesions. In the present case, although the cyst was small and exhibited T2 shading, the patient’s age and high SUV made it difficult to exclude malignancy. Correlation between MRI and pathology indicated that the solid component showed low signal intensity comparable to muscle on both T1WIs and T2WIs, likely reflecting abundant hemosiderin deposition. The mixed low and high signals on diffusion-weighted imaging were considered to result from hemosiderin-induced signal loss and susceptibility artifacts. These findings may aid in distinguishing cholesterol granuloma from malignant tumors, although further case accumulation is needed.

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.