Isolated uterine metastasis from a lung adenocarcinoma

Abstract

A 65-year-old woman was referred with an incidental finding of a flurodeoxyglucose-avid uterine lesion, following excision of a local lung adenocarcinoma. MRI had features concerning for an atypical fibroid or smooth muscle tumour of uncertain malignant potential. She underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology demonstrated a leiomyoma infiltrated with adenocarcinoma consistent with a secondary lesion from the lung cancer. Among the small number of cases of uterine metastases of extra-pelvic primary cancers reported in the literature, those from lung cancers are very rare. Concerning features for an atypical fibroid included the patient’s age and postmenopausal status, as well as positron emission tomography and MRI findings. A metastatic secondary cancer was not suspected. Diagnosis was only made after histopathological examination. This case represents a very unusual cause of a uterine mass. It demonstrates the importance of thorough preoperative work-up and accurate histopathological assessment.

Background

Uterine masses are common. Benign leiomyomas affect an estimated 70%–80% of women.^1–3 Other less frequent but important causes include atypical fibroids, smooth muscle tumours of uncertain malignant potential or primary extrauterine neoplasms.⁴ Malignant causes include uterine sarcomas and endometrial primary malignancies as well as malignancies from another reproductive tract primary.^{5 6} These differentials need to be considered in women presenting with a uterine mass and particularly in the presence of known risk factors for uterine sarcomas, such as postmenopausal status, increasing size and tamoxifen use.^{7 8} Metastases from extra-pelvic primary cancers are a rare cause of a uterine lesion.⁹

Case presentation

A 65-year-old woman with recently diagnosed and surgically managed lung adenocarcinoma was referred with an incidental finding of a flurodeoxyglucose (FGD)-avid mass, measuring approximately 9×9 cm (figures 1–3). She had no postmenopausal bleeding or discharge.

Figure 1.

Pulmonary primary lesion and uterine secondary on coronal. (A) Positron emission tomography and (B) T2 MRI with arrow to lesion.

Figure 2.

Uterine metastasis, sagittal. (A) Positron emission tomography; (B) T1 MRI; (C) T2 MRI with arrows to lesion.

Figure 3.

Uterine metastasis on axial. (A) Positron emission tomography; (B) T1 MRI; (C) T2 MRI; (D) diffusion weighted imaging with arrows to lesion.

On the referral positron emission tomography (PET) study the uterine mass was measured at 92×87 mm and appeared fibroid-like, with an unusual rim of moderate intensely FDG-avid internal soft tissue surrounding a 35 mm central core of inactive tissue. An additional 30-mm FDG-avid hypodense lesion was found abutting the right posterolateral wall of the uterine mass.

The patient had undergone a robotic left upper lobectomy of a 35 mm lung cancer. Histopathology showed a poorly differentiated adenocarcinoma, margins were clear and lymph nodes were negative. The recommendation for subsequent management was for observation and monitoring with no adjuvant therapy.

The patient’s medical history also included longstanding ulcerative colitis, tuberculosis and hypercholestolaemia. Her medications included sulfasalazine, mesalazine, isoniazid and pyridoxine, and rosuvastatin. While she had recently quit smoking, the patient had a history of about one pack of cigarettes a day for 40 years. She had had two normal vaginal deliveries and no significant prior gynaecological history, having been through menopause in her mid-50s and Pap smears were up-to-date. No relevant family history was noted.

Abdominal examination was unremarkable, with no masses felt and no pain reported. A mobile and 12-week-sized uterus was noted on bimanual examination.

Given the concerning features on initial imaging, MRI and lactate dehydrogenase (LDH) level were performed to better characterise the lesion.

Investigations

The patient’s LDH was 688 U/L (normal range 313–618). Routine full blood count, electrolytes, biochemistry and liver function tests were unremarkable.

On MRI, the lesion was noted to be transmural in the right body, displacing the endometrium to the left and measuring 92×82×70 mm (figures 1–3). It demonstrated predominantly low T2 signal, but with marked high signal T2 component at the upper right internal-lateral portion, with associated heterogenous restricted diffusion and contrast enhancement and loss of margin. The endometrium was distorted by the lesion but of otherwise normal appearance. A 27 mm simple cyst was noted on the right ovary. The only previous pelvic imaging was from 15 years prior and did demonstrate a large single subserosal fibroid of 100×105×79 mm in the anterior-fundal region.

The overall impression from imaging was of a likely atypical fibroid of smooth muscle tumour of uncertain malignant potential (STUMP) tumour. Given these findings, the case was referred for review at a combined gynaecology oncology and radiology meeting.

Differential diagnosis

The two preoperative differential diagnoses were a STUMP or an atypical fibroid. First, while PET-avidity is commonly seen in leiomyomas in premenopausal women, the characteristic ‘hollow ball’ sign suggestive of an area of coagulative tumour necrosis, and the finding in a postmenopausal woman were more concerning.^10–12

The patient had a mildly elevated LDH level which has been shown to be associated with increased mitotic rates seen in STUMPs and leiomyosarcomas.^13–15 This however is not specific and different levels and types have been reported as significant.

Findings on MRI suggestive of an atypical fibroid or STUMP included the heterogenous texture, marked restricted diffusion and loss of margin.¹⁶ While a leiomyosarcoma could not be ruled out, it was thought to be less likely as it is a very rare condition and typically presents with evidence of local spread on imaging.⁸ A metastatic secondary cancer was not suspected.

Treatment

Following review of the case by gynaecology oncology and radiology, decision was made for a total abdominal hysterectomy and bilateral salpingo-oophorectomy with peritoneal washings. The abdominal route was chosen over laparoscopy to avoid morcellation of the large mass and thus possible spread and check for any disease dissemination in the case of a malignant cause.

The operation was performed by the general gynaecology unit and was surgically uncomplicated. At the time of surgery, a large fundal fibroid was noted. The patient had an uneventful post-operative recovery.

Macroscopic examination of the total hysterectomy and bilateral salpingo-oophorectomy specimen (figure 4) demonstrated an 87×84×86 mm circumscribed mass, with a whirled, grey cut surface with opaque yellow discolouration suggestive of necrosis. At the myometrial interface, there was a 50×45×18 mm irregular area of haemorrhage and necrosis. There was no involvement of endometrium or serosa.

Figure 4.

Macroscopic pathology fibroid with tumour extending into the myometrium.

Microscopic examination (figures 5 and 6) showed a hyalinised leiomyoma infiltrated by a moderately to poorly differentiated adenocarcinoma, likely representing a metastasis; endometrium was inactive, cervix as well as bilateral fallopian tubes and ovaries were unremarkable and the peritoneal washings were negative. In view of patient’s significant medical history, a broad panel of immunohistochemical stains was performed to include those associated with lung adenocarcinoma. Tumour cells were found to be cytokeratin 7 and thyroid transcription factor-1 (TTF-1) positive and cytokeratin 20, paired box gene 8 and GATA3 binding protein negative. This confirmed the diagnosis of a uterine metastasis from a primary lung adenocarcinoma.

Figure 5.

Microscopic histopathology H&E staining. (A) ×10 and (B) ×20 magnification.

Figure 6.

Microscopic histopathology. (A) Cytokeratin 7 and (B) thyroid transcription factor-1 staining.

Outcome and follow-up

The patient was contacted on the diagnosis and her postoperative review brought forward to discuss the unexpected findings. The gynaecology unit liaised with her oncology/cardiothoracics multidisciplinary team. The patient had an MRI brain, which was normal. Following review of the patient and discussion about treatment options, decision was made for no further adjuvant therapy. Twelve months after the surgery, the patient remains well with no concerns regarding disease recurrence on regular reviews and currently three-monthly CT scans of the chest, abdomen and pelvis.

Discussion

Lung cancer is the most common cause of cancer morbidity worldwide.¹⁷ Metastases from lung cancers are typically found in the lungs, liver and adrenal glands.¹⁸ Only a handful of cases of uterine metastases from primary lung cancers have been reported in the literature to date.^{9 19–23}

Of those reported, there are a number of similarities to that which has been outlined here. The youngest patient was 47 (menopausal status was not reported), the majority were adenocarcinoma and PET was used in all for diagnosis. Unlike this case, most women were symptomatic with abdominal pain and/or abnormal uterine bleeding. Interestingly, while immunohistochemical detection of TTF-1 was used in these cases, many additionally identified an epidermal growth factor receptor gene deletion mutation as part of the diagnosis.^21–23

Looking more broadly at uterine metastases from extra-pelvic malignancies, Kumar and Hart⁹ noted in their analysis of 63 cases that only 4.8% were from lung primaries and most involved the myometrium. Interestingly, nearly all (92%) of the cases were also adenocarcinoma but only 21% were found in a leiomyoma. However, the majority had concomitant ovarian metastases.

Uterine metastases from extra-pelvic primary tumours are a very rare cause of a uterine mass and thus would not be routinely considered in cases of atypical appearing uterine masses. Careful assessment and work-up can, as in this case, ensure they are managed appropriately.

Patient’s perspective.

I was really sick firstly with very bad diarrhoea. I was bleeding and so they put me in the CT scanner. They told me that I had lung cancer and I then panicked. It was shocking as they were checking for diarrhoea and they found cancer in my lungs. I was then seen at a different hospital, who stopped the bleeding and diarrhoea. They then did more imaging and then I had the robotic lung operation. After that they sent me to the women’s hospital clinic and I had another scan and then was told I needed another operation. After this operation, I had a lot of pain. It was very difficult for me.

I was very energetic before these operations. My whole body has now changed. I have put on ten kilograms. But I don’t care, I am healthy. I am very careful now and take all my tablets. I am alright. I am sometimes short of breath when I am shopping after the lung operation, but I still do all my shopping. Since then I have had many checks and imaging that have been normal.

Learning points.

• Unusual uterine masses, especially in postmenopausal women need a thorough work-up.

• Imaging, in particular MRI is useful for assessing for suspicious features.

• A rare cause of a uterine lesion is metastatic disease from an extra-pelvic primary malignancy.