1.Wurzburg University Hospital, Department of Obstetrics, Gynecology, Josef-Schneider-Str. 4, 97080 Wurzburg, Germany
Disease definitionA tumor is classified as primary fallopian tube tumor when it is either restricted to this anatomical structure, or when the fallopian tube is most affected whereas co-locations such as ovary and uterus show lesser involvement or a different histology (Alvarado-Cabrero et al., 2003; Folkins et al., 2009). As recent data indicate that the fallopian tube is the site-of-origin of serous pelvic carcinomas (Folkins et al., 2009; Dietl and Wischhusen, 2011; Dietl et al., 2011; Seidman et al., 2011; Vang et al., 2013), histological assessment of the respective involvement of ovaries and fallopian tubes may not be sufficient to distinguish between advanced stages of fallopian tube and ovarian carcinomas (Kosary and Trimble, 2002). Inevitably, the considerable overlap between ovarian and fallopian tube carcinomas warrants some coverage of ovarian cancer in this context. Nevertheless, as ovarian carcinomas constitute a well-accepted clinical entity (irrespective of their potential origin from the fallopian tube) they shall largely be dealt with in a separate place.
Borderline tumors of the fallopian tube occur very rarely and can show serous, mucinous or endometrioid differentiations. Histological features resemble those in borderline tumors of the ovary (Alvarado-Cabrero et al., 1997). Mucinous tumors of the fallopian tube can be associated with pseudomyxoma peritonei (McCarthy and Aga, 1988), other mucinous lesions or Peutz-Jeghers-Syndrome (Seidman, 1994). There are also reports about adenofibroma with borderline malignancy. The prognosis seems to be favorable (Zheng et al., 1996; Alvarado-Cabrero et al., 1997).
Precursor lesions: Intraepithelial carcinomaNon-invasive carcinomas of the fallopian tube were formerly known as "carcinoma in situ". This term should be abandoned as it implies restricted local tumor formation. Intraepithelial carcinoma cells can, however, form implants on the ovarian surface and the peritoneum. Recent publications highlight the fallopian tube as likely site-of-origin of primary pelvic serous carcinomas detected in the fallopian tube, the ovary or the peritoneum (Folkins et al., 2009; Dietl and Wischhusen, 2011; Dietl et al., 2011; Seidman et al., 2011; Vang et al., 2013). Serous tubal intraepithelial carcinomas (STIC) as well as endometrioid intraepithelial carcinomas (EIC) are thus considered as precursor lesions (Ambros et al., 1995; Carlson et al., 2008). This hypothesis is supported by findings from Colgan et al. who found a high frequency of pre-cancerous lesions in fallopian tubes from patients with BRCA gene mutations (Colgan, 2003). Lee and colleagues could detect mutant p53-signatures predominantly in epithelial cells at the fimbriated ends of fallopian tubes from patients with BRCA1 and 2 mutations. Moreover, the same signatures were also found in corresponding ovarian cancer tissues (Lee et al., 2007). Interestingly, Li-Fraumeni-Syndrome - which is associated with p53 mutations and generally increased risk for serous carcinomas - does not correlate with a higher incidence of PPSC, especially fallopian tube carcinomas. Thus, it seems that other mutations e.g. those affecting BRCA are required to drive PPSC development (Xian et al., 2010). Kim and colleagues could prove by histology that serous epithelial cancers develop in the fallopian tubes of Dicer-PTEN-double-knockout mice. By histology and pathological behavior these tumors showed characteristic traits of serous epithelial ovarian cancer, even though oophorectomy was not protective. Instead, tumor development could be prevented by salpingectomy (Kim et al., 2012). Furthermore, in prophylactic salpingo-oophorectomy specimen, occult carcinomas are more frequent in the fallopian tube than the ovary (Vang, 2011). While carrying the potential of invasiveness, the STIC cells grow sparing the tubal stroma. Figure 3 focusses on the STIC with its distinct cellular alterations such as polymorphic nuclei, multilayer epithelium and atypic mitoses. Figure 3d also shows an invasive fallopian tube carcinoma with an adjoining STIC. In clinical studies, a frequent coexistence of pelvic serous carcinoma and tubal intraepithelial carcinomas was found in unselected (Przybycin et al., 2010) and BRCA mutated patients (Kindelberger et al., 2007). Shortening of telomeres is another early event in PPSC development and already detectable in the STIC (Kuhn et al., 2010). As the post-reproductive fallopian tube lacks physiological functions and also causes complications such as hydrosalpinx, Dietl et al. suggested combined hysterosalpingectomy instead of simple hystercectomy or salpingectomy as a recommendable method for sterilization in clinical routine (Dietl and Wischhusen, 2011; Dietl et al., 2011).
Invasive carcinomaAll tumor subtypes in the ovaries are also known in the fallopian tube, with serous carcinomas being most frequent. In a series of 105 fallopian tube carcinomas Alvarado-Cabrero et al. found the following distribution of different histologies: About 50% were serous, 25% endometrioid, 20% transitional cell or undifferentiated carcinomas and 5% were of other subtypes (Alvarado-Cabrero et al., 1999). Serous adenocarcinomas are generally invasive with 50% G3 tumors (Alvarado-Cabrero et al., 1999). Sometimes immune cell invasion disguises the tumor as salpingitis (Cheung et al., 1994).Mucinous adenocarcinomas, a very rare entity, are often associated with other mucinous carcinomas of the female genital tract or the appendix (Seidman, 1994). Endometrioid adenocarcinomas are very often non-invasive or superficially invasive and show a favorable prognosis (Navani et al., 1996). A part of those tumors displays characteristics of the wolffian adnexal tumor (Daya et al., 1992; Navani et al., 1996).Clear cell adenocarcinomas account for 2-10% of all fallopian tube carcinomas (Voet and Lifshitz, 1982; Hellstrom et al., 1994; Alvarado-Cabrero et al., 1999). Transitional cell carcinomas are rare in the genital tract. Still, the frequency between 11 and 43% of all fallopian tube carcinomas makes it an important locus-specific entity (Uehira et al., 1993; Alvarado-Cabrerog et al., 1999). Undifferentiated carcinomas lack any patterns of squamous cells or glandular cells but instead contain multinuclear giant cells (Alvarado-Cabrero et al., 1999).Lacy et al. reported immunohistochemical positivity for c-erbB-2 (HER-2/neu) overexpression in 26% and p53 positivity in 61% of all cases in a cohort of 43 patients with fallopian tube carcinoma. There was not significant correlation with survival (Lacy et al., 1995). Ovarian cancer in comparison also shows c-erbB-2 (HER-2/neu) positivity in about 29% of all cases (Lanitis et al., 2012). Others, in contrast, described a correlation between p53 immunohistochemical positivity and shorter survival (Zheng et al., 1997; Rosen et al., 2000). FIGO stages, however, did not correlate with survival in this same cohort of 63 patients (Rosen et al., 2000). Zheng et al. investigated the correlating immunohistochemistry and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) for p53 in 52 cases of fallopian tube carcinoma and 10 normal fallopian tubes and found that p53 alterations already occur at early stages suggesting a role in early tumor progression (Zheng et al., 1997). Chung and colleagues found that survival neither correlated with immunohistochemical p53 positivity nor with cMyc overexpression (which occured in 61%). However, the statistical power of this study was limited by the small cohort of 18 patients (Chung et al., 2000). Hence, it did not challenge larger studies which proposed that p53 might have an important role especially in familial BRCA-associated cases of fallopian tube carcinomas. Figure 2 shows different pathohistological aspects of a serous adenocarcinoma of the fallopian tube.
Mixed epithelial-mesenchymal tumorsThe least common site for malignant Müllerian mixed tumor (carcinosarcoma, metaplastic carcinoma) is the fallopian tube accounting for only 4% of all cases. The prognosis of these mostly postmenopausal patients is poor (Hanjani et al., 1980).In the literature, only one adenosarcoma has been described in the fallopian tube (Gollard et al., 1995).
Soft tissue tumorsLeiomyosarcomas are very rare as only 37 cases have been reported in 100 years (Jacoby et al., 1993).
Mesothelial tumorsAdenomatoid tumors mostly occur in middle-aged or elderly women (Inoue et al., 2001). In most cases, they remain asymptomatic but can also occlude the lumen. Often, they show gland-like structures with a lining of flat to cuboidal cells (Stephenson and Mills, 1986).
Germ cell tumorsUntil 2003, 50 cases of mature or immature teratoma were reported (Alvarado-Cabrero et al., 2003). For malignant mixed germ cell tumors of the fallopian tube, only one single case was published (Li et al., 1999).
Trophoblastic tumorsOnly about 4% of choriocarcinomas occur in the fallopian tube (Dekel et al., 1986). About 40% of these go along with adnexal tumors (Ober and Maier, 1981). In the fallopian tube, hydatiform moles can histologically correspond to a complete, partial or invasive mole (Alvarado-Cabrero et al., 2003). Placental site nodules as non-neoplastic proliferation of intermediate trophoblast can occur (Alvarado-Cabrero et al., 2003). Intermediate trophoblast tumors can be either benign or malignant (Kurman et al., 1976). Only one case of malignant placental site trophoblastic tumor has been reported in the fallopian tube (Su et al., 1999).
Lymphoid and haematopoietic tumorsMalignant lymphoma and leukemia mostly show an involvement of the ipsilateral ovary (Osborne and Robboy, 1983). 25% of patients with ovary lymphomas had a Burkitt-lymphoma or Burkitt-like lymphoma or a diffuse large-cell lymphoma.
Metastatic tumorsFor 89% of secondary tumors in the fallopian tube, the primary tumor was assigned to be of ovarian origin (Woodruff and Julian, 1969). Considering the ongoing paradigm shift which proposes that serous ovarian carcinomas likely originate from the fallopian tube, these figures have to be reconsidered. Many of these tumors may have originated from the fimbriated end of the fallopian tube with a secondary manifestation in the ovary.
For the treatment of relapse, platinum-sensitive tumors (relapse after more than 6 months) receive a reinduction with platinum with or without Paclitaxel, whereas patients with platinum-refractory (relapse during therapy) or platinum-resistant tumors (relapse
Roland Gregor Stein ; Joachim Diessner ; Arnd Hönig ; Jörg Wischhusen ; Johannes Dietl
Fallopian tube tumors: an overview
Atlas Genet Cytogenet Oncol Haematol. 2013-03-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5279/fallopian-tube-tumors-an-overview