A case of prostatic carcinosarcoma with cytological and immunohistochemical findings

Prostatic carcinosarcoma (PCS) is an extremely rare malignancy and is reported to have a very poor prognosis. A 77-year-old Japanese male was diagnosed as PCS containing two components, adenocarcinoma and leiomyosarcoma by the immunohistochemical analysis. Cytology was initially useful for the diagnosis. Treatments with androgen ablative and surgical therapies could not improve the patient’s life, and he died at 12 months after the first visit.


Background
Prostate cancer which is often found after elevation of serum prostate-specific antigen (PSA) value, is one of the most common cancers in men. Morphologically, most of the prostate cancers are adenocarcinoma [1,2], although non-epithelial malignancies are known to develop in the prostate [3] with an incidence of less than 0.1% of all prostate malignancies [4]. Prostatic carcinosarcoma (PCS) which was first reported in 1967 by Hamlin and Lund [5], is an extremely rare malignancy and has very poor prognosis with a survival of approximate 7 months [6][7][8][9]. PCS is a histological mixture of adenocarcinoma and certain type(s) of sarcoma [1,2,10]. Approximate less than 100 PCS cases have been reported in the prostate [4]. Some PCSs may also be referred to as sarcomatoid carcinoma [6][7][8][9]11]. Also, only a few studies on the cytological and immunohistochemical findings of this rare malignancy were described [12,13].
We report here cytological, histopathological, and immuohistochemical findings of PCS which developed in a old Japanese man.

Case presentation
A 77-year-old Japanese male noticed macro-hematuria and visited to the Department of Urology in our hospital. On digital rectal examination, a diffusely enlarged lesion on the left lobe of the prostate was palpable. Serum PSA was slightly elevated: 4.03 ng/dL (<4 ng/dL).
MRI showed a cystic lesion with irregular margin on the left lobe of the prostate and partially invaded over the outer layer (Figure 1). A subsequent biopsy revealed Gleason 5 (3+2) adenocarcinoma (Figure 2) of the prostate. The patient was diagnosed as T3aN0M0 prostate adenocarcinoma by the contrast CT, bone scintigraphy and MRI, and wanted to receive an endocrine therapy. Two months after his first visit, the LH-RH analogue therapy was started. Although the serum PSA level decreased to normal levels at 8 months after the start of the therapy, the patient complained of urinary obstruction. MRI revealed an enlarged prostatic lesion, and trans-urethral resection of the prostate (TUR-P) was performed for the purpose of release of the urinary obstruction. A total amount of 35 g prostate was resected. Histopathological examination on the TUR-P specimen showed neoplasm consisted of a mixture of carcinomatous and sarcomatous components. The carcinomatous component ( Figure 3A high-power fields (hpf ). These findings suggested that sarcomatous component was leiomyosarcoma.
Heterogeneous components, such as osteosarcoma and osetosarcoma could not be found. Retrospective examination of the prostatic biopsy showed the presence of non-epithelial atypical cells (Figure 4) with weakly positive reaction with SMA. Thus, the patient could be diagnosed as PCS at his first visit. Although TUR-P had been performed, the tumor rapidly enlarged and obstruction of the urine occurred again. Therefore, the total pelvic exenteration (PE) with cutaneous ureterostomy and colostomy were performed. Macroscopically, the resected prostate tumor was measuring 8x4.5x4 cm (Figure 5), and the surgical margins were free from the tumor. Cytology of the cut-surface of the tumor at the PE revealed the presence of two types of tumor cells with different origin: one was an adenocarcinoma like cells with a sheet formation (Figure 6A), and the other was big sarcomatous cells with a marked nuclear    We performed cytological diagnosis of the present case, as the cytological findings were useful for the diagnosis of the PCS [12,13]. In PCSs reported, adenocarcinoma was usually high grade [6]. Interestingly, some cases were reported to be adenosquamous carcinoma, which may be associated with chondrosarcoma development [6,17]. The most common sarcomatous component was reported to be osteosarcoma (50-62%) followed by chondrosarcoma (33-45%), leiomyosarcoma (17-24%), and rhabdomyosarcoma (10-12%) [6,7]. In the present case, the sarcomatous component was leimomyosarcoma based on the immunohistochemical findings showing positive reaction with α-SMA. From the cytological findings, the epithelial component was diagnosed as adenocarcinoma, however the sarcomatous one could not be diagnosed as leiomyosarcoma because of the presence of a few sarcoma cells.
The mean age at the diagnosis of PCSs is 66 year-old, and the survival period was extremely short, being approximate   ( Figure 7C) and desmin ( Figure 7D) patient was detected as a local recurrence and died at 12 months after the first visit, although we did not detect distant metastasis.

Discussion
The origin and pathogenesis of PCSs is still unknown; some authors proposed that both carcinoma and sarcoma simultaneously developed within the prostate, while others suggested that adenocarcinoma underwent transformation into sarcoma [7,9,14,15]. The present case was suggested to be the latter case from the findings of histopathological re-examination of the biopsy. A recent report by Rodrigues, et al. [16] described deletion of a prostate-specific erythroblast transformation-specific (ETS)-related gene in both the sarcomatous and adenocarcinoma, suggesting that PCSs are derived from prostate epithelium.
Although half of PCSs have developed in patients with a history of prostatic adenocarcinoma [6,8], immunohistocehmical examinations was performed in a few cases [12,13]. In our case, we observed multi-nucleated large sarcomatous cells KN SM YY SY TT