Keywords
abnormal uterine bleeding - adolescence - Burkitt lymphoma
Palavras-chave
hemorragia uterina anômala - adolescência - linfoma de Burkitt
Introduction
Abnormal uterine bleeding (AUB) and heavy menstrual bleeding (HMA) constitute a few
of the main gynecological problems. They are more frequent in adolescence and one
of the main reasons for referral to gynecology consultation in this age group.[1]
[2]
[3]
[4]
The etiology of AUB can be structural or not. Nonstructural causes are more frequent
in adolescence, mainly ovulatory dysfunction, physiological or not, followed by coagulopathies.[2]
[3]
[4]
[5]
[6] However, any cause described can occur at this age and a multifactorial etiology
is common. Therefore, it is imperative to not exclude any cause before a thorough
work-up simply because of age, even malignancies, which are rarely present.[5]
[6]
[7]
[8]
Clinical Case
We present the case of an adolescent, 12 years old, healthy, who had the menarche
in the previous month with adequate menstrual flow for 7 days. She presented to the
emergency room for menstruation with increased flow for 9 days (between 10 and 15
patches/day), and persistent vomiting. The patient had no other symptoms, especially
those compatible with coagulopathy.
She was referred to gynecology due to progressive worsening of heavy menstrual bleeding
and severe hemodynamic repercussion (severe anemia with Hb 7.3 g/dl, 117,000 platelets
and a normal summary coagulation study). At the gynecological examination, an intact
hymen and abundant vaginal bleeding with clots were observed. A rectal examination
was performed, and it was suggestive of a mass on the posterior wall of the vagina,
which on palpation worsened the blood loss through the vagina.
Abdominal and rectal ultrasound was suggestive of a bicorporal uterus, with a noncommunicating
left hemicavity with echogenic liquid content compatible with hematometra, and a right
hemicavity with irregular endometrial thickening (24.8 mm of greater anteroposterior
dimension); and an enlarged right ovary (57 × 41mm), dense stroma, and dispersed vascularization,
without cystic formations ([Fig. 1]).
Fig. 1 Abdominal and rectal ultrasound scan showing “bicorporal uterus, with a right hemicavidity
with irregular endometrial thickening”.
Abnormal uterine bleeding due to ovulatory dysfunction was admitted, eventually exacerbated
by undiagnosed coagulopathy. The patient was started on antifibrinolytics (intravenous
tranexamic acid), estroprogestative (high dose combined oral hormonal contraception)
and transfusion support. Due to worsening of the hemorrhage, she underwent therapy
with a gonadotropin agonist. On the 3rd day of hospitalization, due to severe worsening with hemodynamic instability refractory
to medical treatment, a gynecological examination was performed under sedation. A
vagina with blood clots and a rough anterior wall, mainly in the upper third and hypertrophic
single cervix, was observed. A partial aspiration of the right uterine hemicavity
was performed, with significant hemorrhage reduction. The aspirated material was sent
for analysis and the histological diagnosis was Burkitt lymphoma. Subsequently, complementary
exams showed multiorgan impairment (hepatic, renal, breast, and ovarian). The patient
was transferred to the Portuguese Institute of Oncology where the remaining diagnostic
work-up also showed infiltration of the central nervous system. She was successfully
treated with vincristine, cyclophosphamide, rituximab, methotrexate and arabinosine
C, having been in remission for 5 years ([Fig. 2]).
Fig. 2 Computed tomography images with evidence of uterine and ovarian involvement due to
previously diagnosed Burkitt lymphoma.
Discussion
Abnormal uterine bleeding can be acute or chronic: acute requiring immediate intervention,
whether episodic or in a chronic context; chronic if present in most of the preceding
6 months.[1]
[2] It affects between 10 and 20% of women and is more prevalent in adolescence. The
evaluation of the menstrual cycle, as an additional vital sign, allows an early identification
of an abnormal pubertal progression or, as exemplified in our case, the importance
of the menstrual cycle as an initial manifestation of systemic disease.[3]
Contrary to adult age, in adolescence the main causes of AUB are nonstructural, of
which ovulatory dysfunction is the most frequent. When physiological, due to the immaturity
of the hypothalamus-pituitary-ovary-axis, despite being a diagnosis of exclusion,
it appears in more than ⅔ of the cases. When pathological, it occurs due to hyperandrogenism,
hyperprolactinemia, hypothalamic or pituitary dysfunction or thyroid pathology.[1]
[2]
[3]
[4]
Although rare in the general population (1%), coagulopathies are the second cause
of AUB in adolescence: they are present in 20% of adolescents with AUB and in 30%
of those in need of hospitalization. Heavy menstrual bleeding in menarche, even without
a history of coagulopathy, is a frequent form of presentation, and in 50% of cases
the first sign of a coagulation disorder.[5]
[6]
[7]
[8]
[9] The main associated coagulopathy is von Willebrand disease, and ∼ 13% of women with
HMA have a variant of this disease.[2]
[4] Disorders of platelet function, coagulation factors, and thrombocytopenia are also
prevalent in adolescence.[8]
[9]
In this case, HMA in the first menstruation after menarche could lead to the presumptive
diagnosis of coagulopathy. However, the absence of other symptoms of hemorrhagic dyscrasia
and the analytical evaluation performed showed a low probability for this etiology.
As described, the first approach to a patient with acute AUB is to assess signs of
hypovolemia and hemodynamic instability. Subsequently, the etiological investigation
is performed according to the acronym PALM-COEIN (classification system approved by
the Federation of Gynecology/Obstetrics): Polyps, Adenomyosis, Leiomyomas, Malignancy and hyperplasia, Coagulopathy, Ovulatory dysfunction, Endometrium, Iatrogenia and Not classifiable.[2]
[4]
Medical therapy should always be the first approach, being the only one necessary
in 90% of cases of AUB in adolescents: hormonal, with high-dose combined oral contraception
(or oral progestatives, if contraindicated for estrogens) or antifibrinolytic. The
theoretical thrombotic risk in its association has not been proven and the medications
should be combined if monotherapy fails.[4]
[10]
[11] Surgical therapy should be reserved for the failure of medical therapy or hemodynamic
instability.[2]
[8]
As recommended, in our case, in the face of AUB refractory to medical therapy with
clinical instability, uterine aspiration was performed. This was a difficult decision,
but one which allowed an early definitive histological diagnosis.
Intrauterine balloon tamponade (Foley catheter) could be an alternative, but with
the disadvantages of not allowing histological diagnosis and having a proven use only
in the postpartum period.[8]
[12]
The use of gonadotropin agonists, even when refractory to medical therapy, is questionable.
These play some role in severe chronic AUB but have limited use in acute AUB (due
to flare up and response time). In this context, its use was due to the initial suspicion
of a nonstructural cause and an attempt to avoid more invasive measures due to the
age of the patient.
Burkitt lymphoma is a fast-growing tumor rarely diagnosed in adolescence. It can be
classified as endemic, sporadic or associated with immunodeficiency. As a rule, it
has a high 5-year survival rate (between 60 and 85%) but may have an adverse prognosis
in the rare presence of genital involvement. Given its high response to chemotherapy,
timely diagnosis and treatment is essential.[13]
[14]
[15]
With the presentation of this case, we intend to alert to the approach of severe acute
AUB in adolescence and to the possible less frequent structural etiologies in this
age group. Although rare, the possibility of neoplasia must be considered in the diagnostic
work up to enhance the appropriate treatment of our patients.
