Introduction
Sarcomatoid carcinoma (SC) is one of the rare malignancies of the prostate, which comprises of malignant epithelial and mesenchymal components [1,2]. It is also known by different names such as spindle cell carcinoma, carcinosarcoma (CS), metaplastic carcinoma and malignant mixed mesodermal tumor [2]. In the prostate, it may occur spontaneously or after treatment of an adenocarcinoma, usually of the acinar type. This transformation is supposedly associated with over expression of p53 gene [3]. Less than 100 cases have been reported so far in the English literature in the form of case reports or small case series to the best of our knowledge. [1]. Because of the paucity of cases, little is known about the optimal treatment strategy. However it is known to have an aggressive behavior with an extremely poor prognosis [3,4]. Surgical resection has been recommended for the localized diseases and non-surgical treatments (hormonal, radiation or chemotherapy) are generally associated with poor outcomes. [5] Herein we report an uncommon case of SC of prostate in a 57-year-old man.
Case History:
A 57 years old man hailing from coastal Karnataka presented to Urology outpatient department with complaints of increased frequency and urgency of micturition since the past 4 months. He also complained of altered bowel habits since 1 month. There was absence of associated fever, purulent urethral discharge, weight loss, backache, and family history of prostatic cancer. There was no history of haematuria in the past. He denied any habit of smoking or alcohol intake. Digital rectal examination revealed a stony hard prostate with grade II prostatomegaly. Inguinal lymph nodes were not palpable and physical examination was unremarkable. Serum Prostate Specific Antigen (PSA) levels were within normal limits (2.23 ng/ml). Ultrasound abdomen revealed grade II prostatomegaly with indentation of bladder base. Bilateral kidneys and ureters were normal.
In view of the history and per rectal findings, a transrectal trucut biopsy of the prostate was done. [Figure 1A] Histopathological examination revealed two linear prostatic tissue bits with tumor composed of spindle shaped cells arranged in dyscohesive sheets. The cells had eosinophilic cytoplasm, indistinct cytoplasmic borders, spindled to elongated nuclei with few showing distinct nucleoli. Moderate to severe nuclear pleomorphism and brisk mitotic activity were noted. The spindle and pleomorphic cells were seen infiltrating the collagenous stroma. Cells with epithelial differentiation such as acinar/gland formation was absent in the biopsy. Perineural invasion is noted. A diagnosis of prostatic sarcoma/spindle cell tumor was suggested with a Gleason score of 10 (5+5). However, immunohistochemistry (IHC) with cytokeratin (CK) and vimentin showed positivity in the spindle shaped tumor cells, which clinched the diagnosis of SC of the prostate.
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Figure 1: A. Gross images of the prostatic core biopsies. B .The prostatic linear core biopsy shows tumor composed of spindle shaped cells arranged in dyscohesive sheets. The cells have eosinophilic cytoplasm, spindled to elongated nuclei. Moderate to severe nuclear pleomorphism noted. C. The spindle and pleomorphic cells are seen infiltrating the collagenous stroma. D. Perineural invasion is noted. E. Immunohistochemistry with cytokeratin showing positivity in the spindle shaped tumor cells. F. Immunohistochemistry with vimentin showing positivity in the spindle shaped tumor cells. |
The patient was suggested to undergo a bone scan to evaluate for metastasis and treatment with chemo radiation was suggested. However, he declined to undergo any further intervention, was discharged against medical advice and unfortunately lost to follow up.
Discussion:
Sarcomatoid carcinoma (SC) is one of the rare malignancies of the prostate, which comprises of malignant epithelial and mesenchymal components. It is also known by different names such as spindle cell carcinoma, carcinosarcoma (CS), metaplastic carcinoma and malignant mixed mesodermal tumor. Less than 100 cases have been reported so far in the English literature in the form of case reports or small case series [1-2].
In the prostate, it may occur spontaneously or after treatment of an adenocarcinoma, usually of the acinar type. This transformation is supposedly associated with over expression of p53 gene [3].
Sarcomatoid carcinoma of the prostate is a rare biphasic malignant neoplasm composed of admixture of malignant epithelial and spindle cell component or sarcomatous differentiation of the epithelial component. [1,2,4] It is a rare malignancy of the prostate but can occur at other sites such as head and neck, kidney and lungs. [5]
Malignant prostatic tumors with biphasic morphology can be CS or SC. The term CS is applicable to tumors with malignant epithelial and mesenchymal elements. SC is used to describe tumors, which dedifferentiate from adenocarcinoma into sarcomatoid or heterologous elements like bone or cartilage. The latest World Health Organization (WHO) classification, however, advocates use of the term SC for both these lesions [2,6].
The pathogenesis of this tumor is still not clear. Some suggest the mechanism of epithelial mesenchymal transition while others suggest origin from a pluripotent stem cell, which differentiates into both epithelial & mesenchymal components. [2,4] It may develop de novo or may be diagnosed after treatment for an initial adenocarcinoma of the prostate.
The average age at presentation is 70 years; our patient was 57 years at the time of presentation. Patients usually present with symptoms of bladder outlet obstruction, which include frequency, urgency and nocturia. The less frequent, however, significant symptoms are hematuria, weight loss, lower abdominal and lower back pain from metastasis [4,6]. Our patient manifested with symptoms typical of bladder outlet obstruction, however, his serum PSA was normal. The PSA value is rarely elevated in SCs as these tumor cells have undergone dedifferentiation into sarcoma, thereby losing the production of PSA. [6,7,8,10] The normal PSA level in the sarcomatoid variant results in diagnostic delays and results in presentation at late stages. [6]
The presence of a hard, fixed prostate on digital rectal examination prompted us to evaluate with core needle biopsy, which was suggestive of spindle cell tumor. Further, IHC showed strong membrane positivity for CK in the spindle cell component, confirming the diagnosis of SC. Histological diagnosis of SC needs demonstration of both epithelial and mesenchymal components. Epithelial component can comprise of squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma or transitional cell carcinoma, [6] whereas the mesenchymal component can be osteosarcoma, chondrosarcoma [5,7] or rhabdomyosarcoma [8]. The sarcomatoid component may range from 5-99% of the total specimen and it is composed of undifferentiated spindled to pleomorphic cells arranged in the form of fascicles and sheets. [7] IHC usually shows an epithelial component staining positive for EMA and/or CK and PSA while the sarcomatoid component stains positive for vimentin & focally positive for CK.[3,7] Our case showed diffuse membranous staining of the spindle cell component by CK, suggesting its development from a single multipotent cell line. Mesenchymal marker vimentin was used which showed diffuse positivity in the tumor cells. High index of suspicion is required to diagnose a case of SC in case of complete absence of epithelial/glandular differentiation. It is important to suspect a SC on morphology rather than naming it a prostatic sarcoma and doing a panel of soft tissue IHC markers, which has been highlighted in our case. In about half of the cases of SC, the initial diagnosis is usual acinar adenocarcinoma, which has been treated by hormonal and/or radiation therapy. Transformation from acinar adenocarcinoma to SC can take as much as 5 months to 16 years (mean=7 years). However, in our case, the patient was diagnosed as SC in the first presentation. He did not have any previous complaints of lower urinary tract obstruction. These tumors are known to infiltrate the adjacent structures as well as have distant metastasis in quite a short period of time. Differential diagnosis includes some benign lesions (postoperative spindle cell nodule, inflammatory myofibroblastic tumor) or primary prostatic sarcoma, such as malignant phyllodes tumor, leiomyosarcoma, and malignant solitary fibrous tumor. [6]
There is no standard treatment plan for SC because of its rarity. A study on 70 cases of SC prostate done in John Hopkins University, the largest so far revealed that localized lesions have a definite therapy leading to favorable prognosis. [9] The resectable lesions are removed surgically by prostatectomy and followed by radiation. The prognosis for SC is poor, about 55.5% of cases do not respond effectively to chemotherapy [4]. Many of them show distant metastasis and have an aggressive course. The mortality rate is nearly 90% at the end of 2 years [1,6]. Our patient also showed altered bowel habits suggestive of extension to rectum. He, however, declined further treatment.
To conclude, SC is a highly aggressive variant of prostatic carcinoma that has diagnostic and therapeutic challenges. Our case highlights the significance of per rectal examination compounded with biopsy, histopathology and IHC in the diagnosis of this subtype, since the tumor marker levels were not elevated. Lack of PSA elevation leads to delay in diagnosis of the localized stages of this malignancy. There is no successful treatment for the late stages of these truculent cancers; however, the general principle is curative surgical resection with adjuvant chemotherapy, and/or radiotherapy.
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