A Bunch of Grapes in a Snowstorm

Written By: Aurora Jin MD, Edited by Jeff Greco MD.

Case:

29 y/o F G2P1001 at 12w4d by LMP sent to the ED by her Ob/Gyn due to concern for molar pregnancy. At prenatal visit 4d prior to presentation, informal US demonstrated thickened endometrium but no gestational sac or fetal pole. Received a single dose of mifepristone and was noted to have b-hCG >100,000. Had planned for official US & outpatient D&C but came to the ED due to worsening abdominal pain and continued vaginal bleeding & passing of tissue. ED results were notable for b-hCG of 266,775 and TVUS findings suggestive of molar pregnancy. Pt was admitted to the Ob/Gyn service and underwent D&C with no complications. Surgical pathology revealed diagnosis of partial hydatidiform mole.

Molar Pregnancy:

Molar pregnancy (hydatidiform mole) is a premalignant condition that falls along the spectrum of gestational trophoblastic disease, which involves abnormal proliferation of placental trophoblast. Molar pregnancies can either be complete or partial. Complete molar pregnancies are diploid and often have higher hCG levels, leading to symptoms such as ovarian enlargement (due to theca lutein cysts), hyperemesis gravidarum, hyperthyroidism, and early preeclampsia. Partial molar pregnancies are triploid and have lower hCG levels. In addition, unlike complete molar pregnancies, they are associated with the presence of a fetus, but they frequently result in intrauterine fetal demise due to triploidy.

Typical features of molar pregnancy include vaginal bleeding and/or passing of tissue, pelvic discomfort, uterine size greater than dates, and hyperemesis gravidarum. Work-up of molar pregnancy may vary depending on the trimester and presenting complaints but usually involves a quantitative hCG, type & screen, transvaginal ultrasound (TVUS), and uterine evacuation with pathology analysis, which establishes a definitive diagnosis. Though uncommon, the risk of development of invasive gestational trophoblastic disease, such as choriocarcinoma, necessitates accurate diagnosis of this condition.

Technique & Findings:

● TVUS is the imaging modality of choice in evaluating pregnancy and its complications. In molar pregnancy, TVUS can aid in the diagnosis primarily through visualization of abnormal trophoblast, as well as any associated findings.

● In complete molar pregnancy, one typically sees a central heterogeneous mass in the uterus with numerous discrete anechoic spaces, representing hydropic villi.

• This appearance is classically described as a “snowstorm,” “bunch of grapes,” or “Swiss cheese.”

• No fetus or amniotic fluid should be visualized.

• Ovarian enlargement & theca lutein cysts may also be seen due to the higher levels of hCG in complete mole.

●      In partial molar pregnancy, TVUS findings may be less obvious.

• Suggestive signs include abnormal findings in the placenta, such as enlarged cystic spaces or highly echogenic chorionic villi, or an increased transverse diameter of the gestational sac.

• A fetus may be visualized; frequently, there is growth restriction and/or decreased amniotic fluid volume.

• Typically, theca lutein cysts are not found.

● Color and/or power doppler can also be used to assess the vascularity of cystic tissue. This can be variable; however, complete molar pregnancies are more likely to be avascular.

Images:

Fig. 1. Hydropic vesicles within the uterus, represented by anechoic regions scattered throughout a hyperechoic mass in the uterine cavity. This is classically described as a “bunch of grapes” or “snowstorm pattern”. Source: Flores & Smith (The Pocus Atlas).

Fig. 2. Scan from a patient with 1st trimester complete molar pregnancy. The scan shows diffuse vesicular changes in the placenta; the gestational sac is absent. Source: Berkowitz & Goldstein 2009.

Fig. 3. Scan from a patient with 1st trimester partial molar pregnancy. The scan shows focal vesicular changes in the placenta and a fetus with a gestational sac. Source: Berkowitz & Goldstein 2009.

Fig. 4. 6.5 x 3.8 x 3.7 cm left ovarian theca lutein cyst associated with a complete hydatidiform mole. Source: UpToDate.

Fig. 5. Lack of color Doppler signal in hydropic villi in a patient with complete molar pregnancy. Source: Savage et al. 2017.

Fig. 7. Focal intense Power Doppler flow within placental tissue in a patient with incomplete molar pregnancy. Source: Savage et al. 2017.

Fig. 6. Power Doppler flow is present within placental tissue in a patient with complete molar pregnancy. Source: Savage et al. 2017.

Limitations:

●      Classic findings of molar pregnancy on TVUS are less frequently seen in early term and partial molar pregnancies.

●      Missed incomplete molar pregnancies are often misdiagnosed as missed or incomplete abortions.

●      Though rare, the presence of both molar pregnancy and a normal, viable co-twin can further hinder the diagnosis.

●      Lazarus et al. 1999:

• Retrospective review of cases at an urban academic center

• 21 cases of histologically diagnosed complete molar pregnancy

• Mean gestational age of 10.5 weeks (range 4-18)

• Complete molar pregnancy diagnosed prospectively based on TVUS findings in 12/21 (57%) of cases

  • ≥13 weeks: 5/5 (100%) cases diagnosed

  • <13 weeks: 7/16 (44%) cases diagnosed, with 1 additional case in which the diagnosis was considered

• Theca lutein cysts were not observed in a single case

• Other diagnoses included spontaneous abortion, thickened endometrium, retained products of conception (POC), and early intrauterine gestation

●      Savage et al. 2017:

• Retrospective review of cases at an urban academic center

• 70 cases of histologically diagnosed complete (22) & partial (48) molar pregnancies

• Mean gestational age of 10.5 weeks (range 5.5-20)

• Molar pregnancy diagnosed prospectively based on TVUS findings in 86.4% of complete vs. 41.7% of partial molar pregnancies

• In complete molar pregnancy, you were more likely to see larger gestational sacs, abnormal intrauterine tissue, and placental masses

• In incomplete molar pregnancy, you were more likely to see a yolk sac, fetal pole, and a normal or minimally cystic placenta

●      Fowler et al. 2006:

• Retrospective review of cases referred to a trophoblastic disease unit

• 859 cases of histologically diagnosed complete (253) & partial (606) molar pregnancies

• Mean gestational age of 10 weeks (range 5-27)

• Molar pregnancy diagnosed prospectively based on TVUS findings in 79% of complete vs. 29% of partial molar pregnancies

• The most common false negative diagnoses were missed or incomplete abortion; the most common false positive diagnosis was non-molar hydropic miscarriage 

Conclusion:

TVUS can be a useful tool evaluating for molar pregnancy. However, characteristic findings are inconsistently seen, especially in early term and partial molar pregnancies. If there is a high clinical suspicion for molar pregnancy given TVUS findings, patient presentation, and laboratory values, patients should be referred for uterine evacuation & pathological analysis.

P.S. Here’s proof that Mempin knew US at one point in his life.

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References:

1. Berkowitz RS, Horowitz NS. Hydatidiform mole: epidemiology, clinical features, and diagnosis. In Chakrabarti A (Ed), UpToDate. https://www.uptodate.com/contents/hydatidiform-mole-epidemiology-clinical-features-and-diagnosis. Accessed 27 Nov 2020.

2. Berkowitz RS, Goldstein DP. Clinical practice: molar pregnancy. N Engl J Med. 2009 Apr 16;360(16):1639-45. https://www.nejm.org/doi/10.1056/NEJMcp0900696. Accessed 27 Nov 2020.

3. What to know about transvaginal ultrasounds. MedicalNewsToday. https://www.medicalnewstoday.com/articles/323041. Accessed 27 Nov 2020.

4. Flores B, Smith T. Molar pregnancy. The Pocus Atlas. https://www.thepocusatlas.com/obgyn/e1vtfpqwnxqkrh5qpcx1nxleqwequv. Accessed 27 Nov 2020.

5. Ultrasound theca lutein cysts. UpToDate. https://www.uptodate.com/contents/image?imageKey=OBGYN%2F70450&topicKey=ONC%2F3243&source=see_link. Accessed 30 Nov 2020.

6. Lazarus E, Hulka C, Siewert B, Levine D. Sonographic appearance of early complete molar pregnancies. J Ultrasound Med. 1999 Sep;18(9):589-94. https://onlinelibrary.wiley.com/doi/epdf/10.7863/jum.1999.18.9.589. Accessed 30 Nov 2020.

7. Savage JL, Maturen KE, Mowers EL, Pasque KB, Wasnik AP, Dalton VK, Bell JD. Sonographic diagnosis of partial versus complete molar pregnancy: a reappraisal. J Clin Ultrasound. 2017 Feb;45(2):72-78. https://deepblue.lib.umich.edu/bitstream/handle/2027.42/135968/jcu22410.pdf. Accessed 30 Nov 2020.

8. Fowler DJ, Lindsay I, Seckl MJ, Sebire NJ. Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center. Ultrasound Obstet Gynecol. 2006 Jan;27(1):56-60. https://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1002/uog.2592. Accessed 30 Nov 2020.