Benign phyllodes tumor of the distal end of the ureter: an extremely rare case and literature review

Abstract

Background

A phyllodes tumor (PT) is a biphasic fibroepithelial lesion that is most commonly found in breast tissue, whereas it is uncommon in ureter tissue. Only one case has been documented so far. There are some similarities in histology and clinical characteristics between this type of tumor and PT of the female breast: the lesions can be surgically removed, but some recur locally and invade directly into the breast. This case of a primary PT of the ureter is useful for pathologists and clinicians.

Highlights

I feel such great honor to have this opportunity to submit my paper to your magazine. Although this is a case report, There is only one case report published until now regarding benign phyllodes tumor of the distal end of ureter. The mechanism of this tumor still remained unclear. Thus, We hope that our finding will help clinicians and pathologists to understand the diagnosis further, treatment and prognosis of clinical ureteral phyllodes tumors.

Background

Phyllodes tumors (PTs) are fibroepithelial tumors with biphasic differentiation of epithelial and stromal tissues that most commonly develop in female breasts. To date, fewer than 100 cases of PT in the prostate have been reported, with fewer than 15 cases in the seminal vesicles and very few cases in the vermontanum [1, 2]. To date, only one case of ureter PT has been reported in a 69-year-old man [3]. This report describes the case of a 53-year-old female with an unusual ureteral tumor that is similar in morphology to a breast polyp. To our knowledge, this is the second case of such a condition described in the ureter.

Case presentation

We present the case of a 53-year-old woman who was diagnosed with uterine leiomyoma following a past medical history of renal atrophy and hypertension. The patient did not appear to have experienced frequent urination, urgent urination, dysuria, fever, dizziness, or flatulence. On color ultrasonography of both kidneys, ureters, and bladders, the right kidney was found to have atrophy, the right kidney was found to have calculi, and the right ureter was occupied by fluid. Computed tomography (CT) of abdominal revealed the following: right ureteral malignancy, right renal atrophy, and right renal and upper ureteral calculus formation, which was suspected to be urothelial carcinoma by radiologists.(Fig. 1). Furthermore, Computed tomography(CT) revealed a shrunken and hydronephrotic right kidney, as well as dilatation and ureteral stones in the right upper ureter. There was an irregular lesion measuring 6.5 × 6.0 cm in size in the right ureteral orifice on cystoscopic examination. In the rest of the ureter, there were no other noticeable abnormalities. Following laparoscopic nephroureterectomy, partial cystectomy was performed. A two-month follow-up(including CT exminations and telephone consultation) revealed that the patient was disease free.

Fig. 1

US and Computed tomography (CT) images of a ureteral tumor. (A) On color ultrasonography of both kidneys, ureters, and bladders, the right kidney was found to have atrophy, the right kidney was found to have calculi, and the right ureter was occupied by fluid. (B) Enhanced arterial phase abdominal oblique sagittal reconstruction. (C) CT plain scan. (D) Enhanced CT arterial phase (E) Enhanced CT venous phase. the right ureter was thickened, the middle and lower ureters were unevenly enhanced after enhancement

On gross examination, the unilateral kidney had shrunk, and the ureter connected to the kidney was removed. There was an approximately 7.8 × 6.5 cm tumor in the middle and lower ureters.

Microscopic examination confirmed that leaf-like and clefting patterns could be observed in the tumorconsisting of myxoid stroma and peripheral urothelium in the middle and lower ureters, which is similar to a breast PT (Fig. 2A-C). There was no envelop around the tumor, but there was a fairly clear border around it (Fig. 2D-F).

Fig. 2

Results of the histological analysis of the resected tumor. (A-B) Hematoxylin and eosin-stained sections showing a polypoid and lobulated ureteral tumor. (C-D) The stroma appeared spindle shaped and stellate, with no apparent cytological atypia or mitoses (x400). (E-F) There was a relatively clear border around the perimeter of the lesion (×100)

The leaf-like structure was composed mainly of myxoid stroma lining the periphery with the urothelium. Observations revealed myxoid stromal cells with subepithelial condensation of stromal cells (Fig. 2).

The cells in the stroma appeared to be spindle shaped and stellate. Atypical cytology or mitoses were not observed in the stroma (Fig. 2).

As determined by immunohistochemistry, the stromal cells were negative for a panel of markers, such as Vim (Fig. 3A), SMA (Fig. 3B), CK (Fig. 3C), CK5/6 (Fig. 3D), CK7 (Fig. 3E), CK20 (Fig. 3F), CD117 (Fig. 3G), CD99 (Fig. 3H), CD34 (Fig. 3I), Bcl-2 (Fig. 3J), and EMA (Fig. 3L), with a low proliferation index determined by Ki-67 staining (Fig. 3O, approximately 2%). Diffuse immunoreactions of GATA-3 (Fig. 3K), p53 (Fig. 3M), and Her2 (Fig. 3N) were also detected in the urothelium of patients with severe dysplasia.

Fig. 3

The immunohistochemistry of a resected tumor was observed. (A) Positive Vim staining was observed in the stromal component (×100). (B) Negative staining of SMA was observed in the stromal component (×100). (C) Positive CK staining was observed in the urothelia component (×100). (D) Low positive staining of CK5/6 was observed in the urothelium component (×100). (E) Positive CK7 staining was observed in the urothelium component (×100). (F) Positive CK20 staining was observed in the urothelium component (×100). (G) Scattered positive staining for CD117 was observed in the stromal component (×100). (H) Scattered positive staining of CD99 was observed in the urothelium component (×100). (I) Partial positive staining of Bcl-2 was observed in the urothelium component (×100). (K) Positive staining of GATA-3 was observed in the urothelium component (×100). (L) Negative staining of EMA was observed in the urothelia component (×100). (M) Wild-type expression of P53 in the urothelium component (×100). (N) Positive staining of EMA was observed in the urothelia component (×100). (O) Ki-67 staining revealed a 3% proliferation index for urothelial and stromal cells (×200)

Discussion and conclusions

The first known PT was described in 1838 by Johannes Müller [4, 5]. In recognition of their benign behavioral characteristics, they were temporarily designated cystosarcoma phyllodes. Phyllodes tumors were first classified by the World Health Organization in 1982, and they are further divided into benign, borderline, and malignant types [6, 7].

It is estimated that less than 1% of all breast tumors are PTs, which are most prevalent in the breast [8]. The incidence of prostate PT is second only to that of breast cancer [9]. However, fewer than 100 cases of prostate PT have been reported [10]. In addition to the breast and prostate, primary PTs, such as the verumontanum [2] and seminal vesicles [10]. There is a very low incidence of PT in the urinary tract.

Tchrakian et al. first reported the unique PT case of a human bladder PT in 2018, in which a 54-year-old man underwent a partial cystectomy due to multiple recurrences [11]. During histopathological examination, an epithelio-stromal biphasic polypoid tumor was observed in the mucosal layer of the bladder dome. Neither heterologous components nor infiltrative growth was detected. In this case, it was classified as a benign/low-grade bladder tumor.

To the best of our knowledge, only one case of primary ureteric PT has been reported. A leaf-like pattern was observed in our patient, as was biphasic differentiation between the epithelial and stromal layers, as previously reported. We observed that the stromal cells in our patient were spindle shaped and stellate, which was in accordance with benign lesions, such as noninfiltrative borders, bland cytology, few mitotic figures, and low proliferation rates.

Bostwick DG et al. reviewed 23 prostate lobed tumors on the basis of five histological features, including cell size, cell atypia, the number of mitotic images per 10 high-power fields, the stromal-to-epithelial ratio and necrosis [12]. In the PT of the prostate, a lower level, a middle level, and a higher level are distinguished. It will be possible to observe recurrence rates and distant metastases among these three grade levels. Note that the histologic grade of prostate lobar tumors does not indicate the long-term prognosis but that the longer they are present, the more likely they are to be localized and metastasized distantly. Therefore, complete resection is necessary at first diagnosis.

There are few reports of primary lobe tumors in areas other than the breast and prostate and few reports of urinary diseases such as seminal vesicle glands. Primary lobe tumors of the ureter are extremely rare. A case of urothelial carcinoma with a terminal lobe tumor of the ureter was reported by Dang Linlin [3]. She reported that ductal carcinoma in situ occurred in conjunction with a lobe tumor. However, further research is needed regarding the adjuvant treatment of lobular tumors associated with ductal carcinoma in situ or invasive ductal carcinoma. Fortunately, our case was benign with low cell density, no atypia, no mitotic image, no sarcomatosis or invasive behavior, wild-type p53 expression and low proliferation.

In conclusion, It is extremely rare for benign phyllodes tumors to develop in the ureter with some of them showing morphologic overlap with fibroadenoma, suggesting that they may have a common origin. As phyllodes tumors, our case fit the conventional definition. Given the rare occurrence of lobe tumors in the ureter and bladder, no established standard of treatment exists and the prognosis is not clear [13]. It is believed that complete resection of the tumor reduces the risk of recurrence, but there is no specific prognosis, and further close follow-up is needed. There are also some limitations to our manuscript. In order to gather more information, we reviewed the pathological diagnosis of terminal ureteral lobular tumors in our department over the past ten years. Regrettably, only this case was found to be used as a reference by the pathologist. Morever, our follow-up time was too short to provide accurate information about this patient’s subsequent recurrence and metastasis. Further study is needed to establish the clinical significance of this manifestation.