The reported case illustrates an unusual origin of gynaecological IMT. Gynaecological IMT has been previously described in the scientific literature since 1987 [4], being uterine corpus the primary site of the gynaecological IMT cases reported to date in the English-language literature (Table 1) [3–14]. To the best of our knowledge, this is the first report of a patient diagnosed with IMT of cervix origin treated with surgery with a follow up of two years with no recurrent disease.
The current prevalence of IMT of gynaecological origin is difficult to be established due to the low number of published cases and the changing nomenclature and definition throughout the years (plasma cell granuloma, myofibrohistiocytic proliferation, inflammatory pseudotumour) [15]. IMT is classified as a mesenchymal neoplasia of intermediate malignant potential i. The majority of cases are locally aggressive, but distant metastases at presentation and recurrences have been reported in up to 25% of patients [2, 15].
IMT’s etiology remains unknown. Association with previous trauma, infections or inflammatory processes have been suggested [16]. Advances in the understanding of this disease have been achieved within last years with the description of mutations in the gene that encodes for ALK at 2p23 in up to 50% of cases [17].
IMT has been described in several locations, being the lung the most frequent site, followed by omentum, mesentery and retroperitoneum [2]. The diagnosis of an inflammatory myofibroblastic tumour is extremely rare in the female genital tract [12, 18].The average age at diagnosis is 40 years, whereas extrauterine IMT is more commonly diagnosed in children and adolescents. Cervical IMT is, therefore, a very uncommon tumour and, consequently, it is diagnosed at the histopathology analysis of the surgical specimen or biopsy performed with the clinical suspicion of other mesenchymal neoplasia as uterine leiomyomas or leiomyosarcomas [3].
IMT clinical presentation usually consists of local symptoms secondary to the mass effect and systemic symptoms such as fever, weight loss and elevation of acute phase reactants, probably related to the elevation of IL-6 levels [2, 15]. IMT has not specific radiological features. The average size at diagnosis is around 6 cm in diameter [18], in contrast with the larger size of the lesion described in our case, presenting with a mass 10 cm associating mild ureteral dilation. The radiological presentation is variable, depending on the location and the histological components of the lesion, thus modifying the contrast uptake, attenuation or Doppler signal visible at different imaging examinations [19].
Histologically, three basic patterns have been described in IMT. The myxoid pattern is the most common. It is hypocellular and it is characterized by loosely arranged plump to spindle cells in an edematous or myxoid stroma and a mixed inflammatory infiltrate. The second pattern consists of hypercellular regions of fascicular arrangement of spindle cells with elongated plump nuclei resembling smooth muscle cells. The third pattern counts with areas of hyalinized, sparsely cellular collagen. Mitotic activity and necrosis are rarely seen. The inflammatory infiltrate is commonly lymphoplasmacytic [2–3, 20–21]. The presence of aneuploidy and loss of expression of p53 has been related to more aggressive behavior. Approximately half of the IMT have a translocation that activates ALK gene located at 2p23, this mutation is more frequently reported in tumours of gynecological origin, even as high as 80–100% depending on the series [16, 20–22].
ALK status determination is important in this entity. A phase II study investigating the activity and safety of the ALK tyrosine kinase inhibitor, crizotinib, has recently been published showing a benefit in terms of objective response in ALK-positive IMT. This study included patients with locally advanced or metastatic IMT. Crizotinib showed benefit mainly in patients carrying ALK mutations, although the subgroup of patients without ALK mutations also showed a minor benefit [23–24]. In our case, ALK analysis was negative by immunochemistry and FISH and no further molecular analysis could be performed due to lack of optimal amount of tumour cells in the tumour sample for this analysis.
The most common treatment for these tumours consists of surgical excision. In gynecological tumours, the most frequent intervention is hysterectomy, followed by resection by hysteroscopy when presenting as an intrauterine mass [7]. The relapse rate in resected pulmonary IMT is low, about 2%, while in extra-thoracic locations reaches 25%. It is recommended to perform a close follow-up at least the first years after surgery. In patients with bulky or metastatic disease (mainly lung o brain lesions) that are poor candidates for surgical treatment, therapeutic approaches have been proposed with chemotherapy and radiotherapy as well as with non-steroidal anti-inflammatories and corticosteroids [7]. IMT spontaneous remission is unlikely with only a case reported to date in English literature of this phenomena in IMT of uterine origin [25].