Pregnancy Complicated by Rapidly Progressing Vulvar Melanoma: A Case Study

Introduction

Vulvar cancer is an uncommon disease that affects the female genital tract and accounts for only 5% of all gynecological cancers. The prevalence of invasive vulvar cancer sharply rises after the age of 50 years and reaches its highest point between the ages of 65 and 70 years [1]. Vulvar melanoma is a rare gynecological condition, accounting for only 2-10% of all vulvar malignancies [2]. Vulvar melanoma is the second most prevalent type of malignant tumor of the vulva, following vulvar squamous cell carcinoma (VSCC) [3]. Vulvar melanoma typically affects White women aged 50–70 years [4].

Pregnancy-associated cancer occurs in approximately 1 in 1000 pregnancies, and its incidence is rising [5]. Melanoma is one of the cancers that can affect women of reproductive age, with about 35% of women diagnosed in their childbearing years. Melanomas are generally categorized as cutaneous or mucocutaneous, with the latter, including genital melanoma, exhibiting a higher likelihood of recurrence and a poorer prognosis than cutaneous forms [6].

While cutaneous melanoma has a relatively favorable prognosis, with a 91% 5-year survival rate in females [7], mucocutaneous melanoma has a significantly lower 5-year survival rate of 47% [8,9]. Vulvar melanoma is an exceptionally rare subtype, especially during pregnancy, with only 5 cases documented in the literature since 1946 [10–13]. This type of melanoma often carries a poor prognosis due to its high metastatic potential and delayed diagnosis, and it is usually found in postmenopausal women aged 50–70 [13]. Symptoms, which often appear in advanced stages, can include itching, bleeding, abnormal discharge, and a palpable lump. The rarity of vulvar melanoma in pregnancy highlights the importance of awareness and early detection to improve outcomes [2].

Melanomas that develop during pregnancy pose distinctive problems due to difficulties in diagnosis as well as concerns regarding treatment and prognosis. There has been persistent concern that hormonal and immunological changes during pregnancy could negatively impact the progression of melanoma and lead to poorer outcomes [14]. Vulvar malignant melanoma has an unfavorable prognosis, primarily because of the tumor’s biological aggressiveness, hidden nature, lack of early symptoms, thin dermis, delayed discovery, and limited surgical options [14]. Many organizations recommend that women should delay pregnancy for 6–12 months after completing chemotherapy to allow for recovery and avoid conceiving with an oocyte growing during treatment. Chemotherapy can harm oocytes involved in ovulation owing to its effect on rapidly proliferating cells, leading to increased chances of miscarriage and birth abnormalities in pregnancies conceived shortly after treatment [15]. We present a rare case of a successful pregnancy in a 40-year-old woman who had undergone chemotherapy 6 months before conception and experienced aggressive metastasis before and during pregnancy. This case report describes a rare case of melanoma with rapid progression in pregnancy with favorable fetal outcomes and a literature review of the best current recommendations for vulvar melanoma in pregnancy.

Case Report

A 40-year-old G3P2A0 woman, at 6.5 months of gestational age (January 2024), with a history of recurrent vulvar melanoma before pregnancy came to the delivery room of our hospital (referral tertiary hospital) with labor pain 12 hours before admission; the labor pain was getting more frequent, with dysuria for 3 days before admission, urinary hesitancy, and hematuria. The patient also presented with a vulvar mass upon admission.

Figure 1 shows a timeline of the patient’s medical history. She had had a lump in the birth canal since 2020, which was painful and bled easily. She had no history of cervical cancer screening or abnormal skin lesions. Due to her concern about this lump, she went to an obstetrician, underwent a biopsy excision operation, and was administered multivitamin, albumin, and an immunomodulator. The biopsy results in 2020 were consistent with malignant vulvar melanoma. In 2021, a discolored vulvar mass reappeared, and the patient underwent a second excision biopsy at a secondary hospital. Biopsy results in 2021 were consistent with malignant vulvar melanoma. Imaging was not conducted because of limited facilities. The patient was scheduled for chemotherapy but did not attend a follow-up visit. The patient remained lost to follow-up for 1 year. In 2022, she went to a surgeon for a second opinion and then underwent a third biopsy.

Histopathological examination performed in 2022 revealed vulvar melanoma and invasion of the cervix. The patient was classified as having a stage III vulvar melanoma. She was then referred to a tertiary hospital and received chemotherapy (paclitaxel-carboplatin) at a referral tertiary hospital for a total of 6 cycles of neoadjuvant chemotherapy. The dosage administered was paclitaxel 175 mg/m2 IV followed by carboplatin AUC 5-6 IV day 1, repeated every 21 days for 3–6 cycles, and concluded in January 2023. The histopathological result in January 2023 after pathological biopsy during the follow-up post-chemotherapy was consistent with malignant melanoma of the vulva. Figure 2 shows the biopsy specimens of the patient throughout the study period. Chest radiography revealed no intrapulmonary metastasis. Magnetic resonance imaging (MRI) was not performed in the secondary hospital because of the cost to the patient.

On July 2023, she underwent a positive pregnancy check. No concerns were reported between February and November 2023. Previously, she had delivered twice, in 2004 and 2005.

The interval between the second pregnancy and appearance of the vulvar mass was 15 years. Throughout the pregnancy, she underwent prenatal treatment on 4 occasions, with 2 visits to a midwife, 1 visit to the primary healthcare center, and 1 visit to an obstetrician. She underwent antenatal care at the fetal clinic and the fetus was considered healthy. A previous antenatal examination revealed that the pregnancy had no complications.

On December 18, 2023, she reported experiencing hemorrhage from the birth canal. Consequently, she underwent conservative treatment for 2 days at a secondary hospital and was administered medication to promote fetal lung maturation. On December 27, 2023, she reported a recurrence of bleeding from the birth canal and thus received conservative treatment at the referral hospital for 4 days. Her blood pressure was 150/90 mmHg during conservative management, but she did not report any symptoms of headache, upper abdominal pain, or blurred vision. The results of an emergency ultrasonography examination on December 27, 2023, showed a single live intrauterine fetus at 27 weeks of gestation (Figure 3). There were no abnormalities in the fetus, but a 13.24×11.92×10.29 cm hyperechoic solid mass was found in the cervical region (Figure 3). The urinalysis test indicated +3 proteinuria. A diagnosis of severe preeclampsia was established, and the patient was managed according to the national preeclampsia protocol in Indonesia, receiving magnesium sulfate (MgSO4) and methyldopa 2×500 mg as antihypertensive therapy. She was discharged with a stabilized blood pressure of 110/80 mmHg.

Physical examination on admission revealed that she was in a state of full consciousness with normal vital signs. Abdominal examination revealed a uterine fundal height of 25 cm, with no observed contractions, and a fetal heart rate (FHR) ranging from 148 to 152 beats per minute. Genital examination revealed a 3×3 cm exophytic pigmented mass located on the outer vaginal wall (labia majora and minora). The lesion presented with irregular borders and heterogeneous pigmentation, suggestive of malignancy. The mass was accompanied by localized tenderness, raising concerns about the inflammatory response or nerve involvement (Figure 4). No other skin lesions were noted. Internal examination revealed the portio was thick, rigid, and posterior, without dilation. A urinary catheter was inserted, making the urine appear red.

Ultrasonography was performed upon admission. During the urinary bladder examination, the catheter balloon was visible. A dense mass, measuring 14.78×11.34×12.98 cm, was observed in the cervical region (Figure 5). Laboratory examination on February 1, 2024, at the tertiary care center showed an increased lactate dehydrogenase (LDH) level of 471. Preoperative hematology results showed an Hb level of 10 g/dL. Other laboratory results were within normal limits. The patient was diagnosed with suspected stage IV vulvar melanoma (T3NXM1) with high LDH levels.

She underwent surgery, transperitoneal cesarean section, and removal of the uterus and surrounding tissues (type IV radical hysterectomy). We decided to perform cesarean section for the baby due to progression of carcinoma to the uterine corpus, and preeclampsia, which constituted an obstetric indication for pregnancy termination (ICD code: O99.8, O99.2, O.82). Cesarean hysterectomy was performed.

An incision was made in the vaginal wall to access and remove the mass from the uterine corpus (colpotomy due to uterine corpus mass). Lastly, repair was performed on the urinary bladder to fix a tear caused by medical intervention (urinary bladder repair due to iatrogenic laceration). The documentation of the surgical findings is shown in Figure 6.

The procedure was performed under general anesthesia. A female infant was delivered, weighing 1000 grams, with a length of 35 cm, head circumference of 26 cm, and chest circumference of 23 cm. The Apgar score at 1’/3’/5’ was 6/7/8. A thorough investigation revealed the presence of a necrotic tumor measuring 15×10×5 cm. The tumor exhibited an irregular texture and infiltrated the uterus and the cervix. Furthermore, the cancer had formed adhesions with the omentum and the urinary bladder. A type IV hysterectomy was performed, resulting in total removal of the uterus.

Histopathological examination revealed metastasis of the melanoma to the urinary uterine corpus and cervix (Figure 7). There was ±2500 cc blood loss. The patient received 2 units of packed red blood cells during the surgery. The surgery was successful, without any notable complications. The patient received postoperative symptomatic medication (analgesics and antibiotics). Postoperative laboratory results showed Hb levels within normal limits, with a value of 10.8 g/dL.

During the observation period, the infant was treated in the Neonatal Intensive Care Unit (NICU) for 7 days and intubated with continuous positive airway pressure (CPAP) for respiratory assistance. The infant received care in a level 3 perinatology unit and was discharged in a satisfactory condition after 14 days of monitoring. Three months after the cesarean section, the infant was admitted for routine control. The latest reported condition of the baby was good with no developmental delay. No significant concerns were reported during the follow-up period. At the 3-month follow-up, the infant’s weight was 4970 g, length 59 cm, and head circumference 35 cm, but still required frequent monitoring for catch-up growth.

After the surgery, the patient was discharged upon request. She was scheduled to undergo chemotherapy following the surgery, but she did not attend the postoperative follow-up at 1 week. Unfortunately, after 1 month, the patient was admitted to the hospital because of difficulty in eating and anuria. Laboratory results during this admission showed hypoalbuminemia (0.89) and electrolyte imbalance (hyponatremia 133; hyperkalemia 5.12; and hypocalcemia 6.8). The patient underwent electrolyte and albumin correction to improve the overall condition. The condition of the patient deteriorated, and she died 1 month after the surgery.

Discussion

Melanomas during pregnancy present unique diagnostic and therapeutic challenges. Concerns about hormonal and immunological changes affecting melanoma progression are longstanding [13]. Vulvar melanoma is particularly aggressive, often with delayed diagnosis due to its concealed presentation and lack of early symptoms [16]. In our case, the patient had no prior concerns after chemotherapy, but experienced recurrence at 27 weeks of gestation, a period when tumor progression can accelerate due to pregnancy-related changes. The recurrence of symptoms highlights the rapid progression of vulvar melanoma in pregnancy, which is further complicated by hormonal and immune system shifts [14].

Despite limited data, our case resulted in a preterm live birth following a cesarean section due to the progression of vulvar carcinoma. Only a few cases of vulvar melanoma in pregnancy have been reported, emphasizing the rarity of the condition [10–13].

In our case, the patient did report any concerns prior to pregnancy after the completion of chemotherapy. However, symptoms recurred during her admission in the 27th week of gestation. The observation in this case indicates that the progression of incomplete vulvar melanoma during pregnancy occurs rapidly as the fetus grows. The highest incidence of vulvar melanoma is in the labia majora and labia minora. Frequently reported patient concerns include the presence of lumps in the vulva, discomfort, bleeding, and itching, while less common symptoms include uncomfortable urination and ulceration. Patients with vulvar malignancies may have significant delays in diagnosis owing to the absence of symptoms or the presence of non-alarming signs, such as sudden bleeding, which are more commonly observed in other types of gynecological tumors [1,15].

In this case, the patient, aged 40, had not undergone prior cervical cancer screening or exhibited abnormal skin lesions before her diagnosis of vulvar melanoma. She had given birth twice prior to the diagnosis, unlike most cases where patients are younger (average age 31 years) and often nulliparous. Vulvar melanoma has a significantly poorer prognosis, with 40% of cases diagnosed at an advanced stage [1], in contrast to other vulvar cancers, which are often detected earlier and are of lower grade. This case underscores the knowledge gap in understanding melanoma progression and recurrence during pregnancy, particularly in patients with prior full-term pregnancies [1].

Our patient had no regional lymph node metastasis, but exhibited direct expansion to adjacent organs, possibly accelerated by pregnancy. This aligns with findings of rapid tumor progression in advanced cases of invasive vulvar cancer [16]. Elevated LDH levels, as seen in our case, are associated with reduced survival in melanoma patients, indicating an advanced disease stage [1].

The physiological changes in pregnancy, including increased plasma volume and immune system alterations, likely contributed to the rapid disease progression. These changes may enhance tumor growth and spread [13]. Many international organizations recommend that women delay conception for 6–12 months after completing chemotherapy to allow for recovery and to avoid conceiving an oocyte affected by treatment [17]. However, our patient conceived within 6 months, which underscores the variability of chemotherapy’s impact on reproductive outcomes.

Surgical management was challenging due to the tumor’s progression and pregnancy. The patient underwent type IV hysterectomy, colpotomy, and bladder repair. Immunotherapy has shown promise but is limited during pregnancy due to its potential adverse effects on the fetus [18]. A multidisciplinary approach is crucial in such rare cases, with treatment tailored to both the tumor’s characteristics and the pregnancy stage.

The strength of this study lies in its focus on an extremely rare occurrence – vulvar melanoma during pregnancy – alongside a successful pregnancy outcome, which provides valuable insights into the balance of oncological treatment with pregnancy management. Given the limited cases reported, this case contributes practical guidance to the medical literature and may inform future protocols for managing similar complex cases where rapid malignancy progression coincides with pregnancy.

A limitation of this study is the inherent lack of generalizability, as our findings are based on a single patient. While the case adds to the understanding of managing such rare conditions, broader studies are needed to validate this approach. Additionally, we encountered specific challenges that influenced management, including limited standardized protocols for vulvar melanoma during pregnancy, and unique patient factors that could affect treatment tolerance and outcomes. These factors underscore the complexity of balancing treatment effectiveness with maternal-fetal safety, and similar success may not be achievable in other cases.

Conclusions

Vulvar melanoma during pregnancy is exceedingly uncommon. Pregnancy can exacerbate the proliferation and metastasis of cancer cells owing to physiological changes. This case report is an example of the rapid progression of vulvar melanoma in pregnancy that metastasized to the uterine corpus; however, it resulted in a viable live fetus. This paper reports a case of a successful pregnancy following 3 excision biopsy procedures and 6 rounds of chemotherapy. Successful conception within a year after the last administration of chemotherapy indicated that there was no exposure to chemotherapy medications during the period of conception. This report provides important clinical insights into managing a complex case involving a rapidly progressing malignancy while maintaining the safety and viability of the pregnancy.