Most Likely Diagnosis: Leiomyosarcoma (B)
In a postmenopausal woman on tamoxifen presenting with vaginal bleeding and a fibroid that has grown from 2×3 cm to 5×8 cm over 5 years, leiomyosarcoma is the most likely diagnosis. 1, 2
Clinical Reasoning
Why Leiomyosarcoma is Most Likely
Rapid fibroid growth in a postmenopausal woman is highly suspicious for malignant transformation. Benign leiomyomas typically regress after menopause due to declining estrogen levels, making significant growth (from 6 cm² to 40 cm² in this case) a red flag for sarcomatous change. 1
Tamoxifen is specifically associated with uterine sarcomas. The NSABP BCPT trial demonstrated an incidence of uterine sarcoma of 0.17 per 1000 women-years in tamoxifen users versus 0.0 in placebo, with a black box FDA warning highlighting this risk. 1, 2
The FDA label explicitly warns that uterine sarcomas (including malignant mixed mesodermal tumors) occur in tamoxifen-treated patients, with 4 cases reported in the NSABP trials versus 1 in placebo. 2
Postmenopausal bleeding in this context demands immediate tissue diagnosis, as 90% of endometrial cancers present with abnormal bleeding, but the dramatic fibroid growth pattern points more specifically toward sarcoma. 1
Why NOT Endometrial Adenocarcinoma (C)
The endometrium is only 5 mm thick and homogeneous. While tamoxifen increases endometrial adenocarcinoma risk (2.20 per 1000 women-years versus 0.71 for placebo), the ultrasound findings do not support this diagnosis. 1, 2
Endometrial thickness ≥4-5 mm warrants biopsy, but a homogeneous 5 mm endometrium is less concerning than the massively enlarged fibroid. 3, 4
Endometrial adenocarcinoma would typically present with endometrial thickening, irregularity, or focal abnormalities, not with a rapidly growing intramural mass. 1, 5
Why NOT Benign Leiomyoma (A)
Benign fibroids do not grow in postmenopausal women—they shrink due to estrogen withdrawal. This patient's fibroid more than tripled in size, which is pathognomonic for malignancy in the postmenopausal setting. 6
While tamoxifen has partial estrogenic effects that can stimulate fibroids, the degree of growth observed here (from 2×3 cm to 5×8 cm) far exceeds what would be expected from benign stimulation. 2
Why NOT Metastatic Ovarian Carcinoma (D)
There is no mention of ovarian pathology on ultrasound, and metastatic ovarian cancer to the uterus would present with additional findings such as ascites, omental caking, or ovarian masses. 1
The clinical presentation and imaging findings are inconsistent with metastatic disease. 1
Immediate Management Algorithm
The patient requires urgent tissue diagnosis through hysteroscopy with directed biopsy and endometrial sampling, NOT empiric treatment or observation. 3, 4
Office endometrial biopsy has a 10% false-negative rate, so if initial sampling is non-diagnostic, fractional D&C under anesthesia must be performed. 3, 4
Hysteroscopy allows direct visualization and targeted biopsy of the endometrium, while the growing fibroid requires surgical evaluation regardless of endometrial findings. 3
Preoperative pathological information is crucial for establishing the surgical plan—if leiomyosarcoma is confirmed, staging and definitive surgical treatment (total hysterectomy with bilateral salpingo-oophorectomy) should proceed. 3
Critical Pitfalls to Avoid
Never accept reassurance from endometrial thickness alone in a symptomatic tamoxifen user—the 5 mm homogeneous endometrium does not exclude malignancy when a rapidly growing mass is present. 3, 4
Do not attribute postmenopausal bleeding to "benign" fibroid growth without tissue diagnosis—this delays diagnosis of both endometrial cancer and uterine sarcoma. 1, 2
Uterine sarcomas present at more advanced stages and have worse prognosis than endometrial adenocarcinomas, making early recognition critical. 1
Most tamoxifen-associated endometrial cancers present with vaginal spotting as an early symptom, but the dramatic fibroid growth pattern here specifically suggests sarcomatous transformation. 1, 2