Basaloid Carcinoma of the Prostate

1. National Cancer Centre Singapore, Radiation Oncology

2. St Georges Hospital, Pathology

3. University of Surrey, Faculty of Health and Medical Sciences

4. Royal Marsden Hospital, Radiotherapy

Conventional acinar adeno-carcinomas represent the large majority (>90%) of prostate cancers. Variants of conventional prostatic adeno-carcinomas have been described and are important to recognise because the prognosis and treatment may vary substantially. These special variants have a wide histological spectrum and originate from the four types of prostatic epithelium (i.e. secretory epithelium, neuro-endocrine cells, basal cells and transition epithelium). They can occur in a pure form or in association with conventional adeno-carcinomas.

Basal cell carcinoma of the prostate (BCP) is a neoplasm composed of prostatic basal cells. Some tumours resemble its namesake in the skin, comprising large basaloid nests with peripheral palisading and necrosis. Other patterns are similar to florid basal cell hyperplasia or the adenoid basal cell pattern of basal cell hyperplasia (the latter also referred to as adenoid cystic carcinoma). There are only a few publications outlining the diagnosis, treatment, prognosis and outcome for BCP. Traditionally surgery is used but these tumours also respond to concomitant chemo-radiotherapy.

Although most reported BCP are of indolent behaviour (1), there are reports of local recurrence and metastases (2-4). There is a lack of outcome data in BCP reports and their biological behaviour remains uncertain. Due to the limited information on the management and follow-up of BCP, no standard therapeutic approach has been established.

A review of the clinical-pathological features and management options for BCP was undertaken using PubMed, from 1996 to 2009. The keywords used for the search included ‘adenoid cystic’, ‘adenoid cystic-like’, ‘basaloid’ and ‘basal cell carcinoma’ together with ‘treatment’, ‘surgery’, ‘radiotherapy’, ‘radiation’, chemotherapy’ and ‘chemo-radiation’ or ‘chemo-radiotherapy’. Available clinical, histo-pathological, immuno-histochemical, management, outcome and follow-up data were abstracted. The management and follow-up data were reviewed to ascertain the available treatment options for BCP.

Using a BCP case successfully treated with radical chemo-radiotherapy from a regimen used in anal cancers, we propose an alternative management to traditional options of radical surgery and radical radiotherapy. We compared the outcome of our case to that of patients treated with surgery and radiotherapy.

A 78-year-old man presented with lower urinary tract symptoms, nocturia and gross haematuria in November 2002. Examination revealed an enlarged smooth prostate and normal rectum. PSA was 0.8ng/L. An intravenous urogram showed a large prostatic impression into the bladder and significant residual volume post-micturition. Cystoscopy revealed mild trabeculation of the bladder only. Magnetic resonance imaging confirmed numerous cysts within a markedly enlarged prostate (333cc) with atypical T1 and T2 signals. These cysts occupied most of the central gland, compressed the left lateral peripheral zone, extended through the prostatic capsule and invaded the obturator-internus and levator-ani muscles. There was a 2cm lymph node along the left pelvic sidewall. A bone scan was clear of bony metastases.

Histo-pathology revealed BCP with no evidence of conventional prostatic adeno-carcinoma. Malignant sheets of basaloid cells with small islands of keratinising squamous epithelium extensively infiltrated all six biopsy cores. The tumour cells showed mitosis but not necrosis. Immuno-histochemistry focally stained positive for LP34, CAM5.2 and CK 7, but negative for PSA, TTF1, CK20 and chromogranin. There were no histological features of adenoid cystic carcinoma (i.e. cribriform architecture with characteristic basement membrane duplication) and the tumour was morphologically of pure basaloid subtype

 

 

This T4N1M0 prostate basaloid carcinoma was discussed in the multidisciplinary meeting. The patient received concurrent chemo-radiotherapy to 65Gy in 35 daily fractions over 7 weeks from December 2002 to February 2003. Chemotherapy comprised of 10 mg/m2 of Mitomycin on Day 1 and 750mg/m2 of 5-Fluro-uracil given as continuous infusion on Day 1 to 4; during the 1st and 5th week of pelvic radiotherapy. He suffered acute urinary retention after his first chemotherapy cycle. This required urinary catheterisation. The urethral catheter was later changed to a supra-pubic catheter. MRI scan done ten months post treatment showed no residual tumour. The patient remained relapse free until 10 June 2005 when he passed away from a ruptured abdominal aneurysm unrelated to his cancer.

Reports in the literature are confusing, as different investigators have listed BCP under different histological headings. Furthermore there is no consistent management for BCP as the natural history and clinical course can be very variable. The clinical-pathological data available in 61 cases of BCP reported in the literature are shown in Table 1 (2, 5, 6).

The age range of patients with BCP is wide (28–89 years) but BCP is more common in the elderly with a mean and median age of 66 and 68 years respectively. Presenting symptoms are non-specific and may include nocturia, urgency, or acute urinary retention. From Table 1, the main clinical presentation was obstructive urinary symptoms with 42 diagnosed incidentally on trans-urethral resection of prostate (TURP).  On rectal examination, the prostate is usually enlarged and partly indurated. Clinical investigations using serum PSA and preoperative imaging investigations are non-specific; serum PSA can be normal (3) or slightly elevated (2).

BCP is classified in the 2004 World Health Organization (WHO) classification of tumours of the urinary system along with adenoid cystic carcinoma. The WHO classification proposed that malignant basal cell tumours, including adenoid cystic (AC) and basaloid variants, be classified under a single term ‘BCC’. The WHO also issued specific criteria to distinguish benign from malignant basal cell proliferations. Malignant features include an infiltrative pattern, extra-prostatic extension, peri-neural invasion, necrosis and stromal desmoplasia. The primary diagnostic criterion is an infiltrative pattern of desmoplastic stroma. Most of the cases in Table 1 showed a predominantly adenoid cystic pattern, some of mixed pattern and only 6 showed an exclusive basaloid pattern.

Grossly, BCP are white and fleshy, sometimes with micro-cysts, unlike acinar carcinoma, which is usually yellow. These tumours usually show ill-defined, infiltrative edges and involve the transition and peripheral zones. Microscopically, BCP has a broad morphologic spectrum and can be similar to BCC of the skin. The prostate is infiltrated by irregular solid clumps, or trabeculae and larger cellular masses of basaloid cells. The cells have uniform small, round or oval nuclei with scant cytoplasm (7, 8). While there is peripheral pallisading, cribriforming is absent or minimal (7-9).  Occasional glandular, trabecular, and solid areas can be found. The nuclei have basal cell features with angulated nuclear contours, and may be hyper-chromatic or micro-vacuolated. In some cases, sebaceous and squamous differentiation can be seen. Extensive perineural invasion and extra-prostatic extension have been described. Mitoses are absent or only sparsely present. The stroma may show a desmoplastic or myxoid alteration (2).

The pattern of BCP cannot be classified under the Gleason scheme and is not known to correlate with outcome. Therefore Gleason grading is not recommended. According to general consensus, the specific markers for BCP are high molecular weight Keratin and Cytokeratin 14. Usually staining for PSA is negative (10). Other investigators have reported the use of Ki-67 index and Bcl-2 protein for diagnosis of malignancy.

The main differential diagnoses of BCP are benign basal cell hyperplasia and acinar adeno-carcinoma (with a cribriform pattern) [27]. Clinically, the only differentiating factor from conventional adeno-carcinoma is that the PSA is usually normal or only slightly elevated. Although basal cell hyperplasia may have an infiltrating pattern with cellular atypia making diagnosis difficult, this subtype does not extend out of the prostate or into adjacent organs. Other differential diagnoses include metastatic carcinomas and transitional cell carcinoma (TCC). TCC may exhibit a solid growth pattern with peripheral palisading and central necrosis.

Although most reported BCP are of indolent behaviour (1), there are reports of local recurrence and metastases (2-4). Of interest is that metastases often involve liver, lung, and bowel but not bone, as is commonly observed in prostate adeno-carcinoma (2). In one series where outcome is reported, metastasis was documented in 4 of 15 patients (2), following treatment with surgical resection only. From Table 1, local recurrence occurred in 8/62 patients. Metastases developed in 10/62 patients. Median follow-up was 1 year (range 0-19 years) and 27/62 (43.5%) had >1 year follow-up.  Following treatment, there was no evidence of disease recurrence in 38/62 (61.3%). Radiotherapy or chemotherapy may be helpful, but published results are inconsistent (3, 9) (see Table 1).

The diagnosis of BCP requires histo-pathological confirmation. Elevated expression of bcl-2 and high Ki-67 index may aid diagnosis of basal cell proliferative lesions. Furthermore, histo-pathology cannot reliably predict the clinical course.

Due to the presumed indolent nature of BCP and the older age at presentation, most men did not receive definitive therapy beyond the initial diagnostic TURP. Although the biological behaviour is not fully understood, it is now clear that a small subset of BCP have the potential to invade and reoccur locally as well as metastasise. There was local-regional nodal involvement in our patient. We opted for aggressive combined chemo-radiation despite his age. He tolerated treatment well and remained disease-free until death from an unrelated cause 25 months later. Usually surgery is used when disease is confined to the prostate, but where disease extends beyond the prostate, radiotherapy can be considered. With more extensive disease and regional nodal involvement, chemo-radiation is reasonable. To our knowledge, this is the only case of BCP treated with combined chemo-radiotherapy, and treated successfully to complete remission.

Our literature review indicates that BCP is a rare tumour with clinical-pathological features distinct from classical prostate adeno-carcinoma. Whilst surgery has been mainly used, our case showed that combination chemo-radiotherapy is an alternative and/or additional treatment option for BCP.

No.	Age	Predominant Pattern	Specimen	Necrosis	RP findings	Treatment	Prognosis	FU years
1	69	AC-P, Basaloid	TUR	No	–	–	NED	3
2	66	AC-P	TUR	No	–	RT	NED	1
3	60	AC-P	TUR	No	–	–	Unknown	No FU
4	76	AC-P	TUR	NA	–	–	NED	<1
5(3)	60	AC-P/Basaloid	TUR	No	–	RP	NED	6
6(3)	68	AC-P	TUR	No	–	RT	NED	<1
7	NA	Basaloid	NBx	NA	–	–	Unknown	No FU
8(9)	38	AC-P	NBx	No	–	RP, RT	Unknown	No FU
9(2)	28	Basaloid	TUR	No	–	RT, Chemo	NED	2
10(6)	44	AC-P	NBx	No	–	RP, RT	LR	7
11	43	AC-P/Basaloid	NBx	NA	–	RP, RT	Unknown	No FU
12(7)	65	Basaloid	Nbx	–	–	RP	Lung, bone mets	1
13(1)	69	AC-P	TUR	–	–	–	NED	2
14(1)	49	AC-P	NBx	–	–	Extenteration	Lung, para-vertebral mets. DOD	3
15(1)	NA	AC-P	TUR	–	–	–	Liver mets	No FU
16(1)	81	Basaloid	NBx	–	–	RP	Lung corpus cavernosum mets	No FU
17(1)	68	AC-P	TUR	–	–	–	Alive with tumour	6
18(1)	43	AC-P. squamous	TUR	–	–	RP	NED	5
19(1)	46	AC-P	NBx	–	–	Extenteration	Liver colon, DOD	2
20(1)	70	AC-P	NBx	–	–	–	Alive with tumour	2
21(1)	83	AC-P	TUR	–	–	RT	NED	2
22(1)	53	AC-P	TUR	–	–	–	NED	1
23(1)	60	Basaloid, squamous	TUR	–	–	–	Unknown	No FU
24(1)	77	AC-P	TUR	–	–	–	NED	<1
25(1)	87	Basaloid, squamous	TUR	–	–	–	NED	<1
26(1)	82	Basaloid, squamous	TUR	–	–	–	NED	<1
27(1)	55	AC-P	NBx	–	–	RP, RT	Alive with tumour	11
28(1)	74	Basaloid	TUR	–	–	–	Unknown	No FU
29(1)	63	Basaloid	TUR	–	–	RP	NED	5
30(1)	64	AC-P	NBx	–	–	RP	NED	2
31(1)	81	Basaloid	TUR	–	–	–	NED	<1
32(4)	63	Big solid nests	TUR	Yes	–	RT and Chemo	Penile mets, LR	1
33(4)	51	Big solid nests	NBx + TUR	Yes	–	RT	Bone, liver, lung mets	1
34(4)	86	Big solid nests	TUR	Yes	–	–	Lung, LR	2
35(4)	69	Big solid nests	RP	Yes	EPE; MAR+	RP, RT and Chemo	Lung and liver, LR	<1
36(4)	56	Big solid nests	TUR + RP	Yes	EPE; SV+	RP	NED	1
37(4)	53	Big solid nests	TUR + RP	No	EPE; MAR+	RP	NED	1
38(4)	83	Big solid nests	TUR	No	–	–	NA	No FU
39(4)	73	Big solid nests	NBx	No	–	–	NED	9
40(4)	87	Small solid nests	TUR	No	–	–	NED	10
41(4)	65	Small solid nests	NBx	No	–	–	NED	9
42(4)	66	Small solid nests	TUR	No	–	–	NED	6
43(4)	51	Small solid nests	TUR	No	–	–	NED	<1
44(4)	77	Small solid nests	TUR	No	–	–	Unknown	No FU
45(4)	62	Small solid nests	TUR	No	–	–	NED	1
46(4)	76	Small solid nests	TUR	No	–	–	NED	1
47(4)	65	Small solid nests	NBx	No	–	–	NED	<1
48(4)	89	Small solid nests	TUR	No	–	–	Unknown	No FU
49(4)	82	Small solid nests	NBx	No	–	–	NED	2
50(4)	73	Small solid nests	TUR	No	–	–	NED	<1
51(4)	66	AC-P	TUR + RP	No	No Tumour	Pre-RP RT + RP	NED	19
52(4)	74	AC-P	TUR	No	–	–	NED	6
53(4)	76	AC-P	TUR	No	–	–	NED	1
54(4)	70	AC-P	Nbx	No	OC	RP	NED	5
55(4)	66	AC-P	TUR	No	EPE	RP	NED	4
56(4)	78	BCH	TUR	No	–	–	Unknown	No FU
57(4)	76	BCH	TUR	No	–	–	NED	<1
58(4)	69	BCH	TUR	No	–	–	Unknown	No FU
59(4)	42	BCH	TUR	No	EPE	RP	NED	8
60(4)	71	BCH with nodules	Enuc + TURs	No	–	–	NED	11
61(5)	68	Big solid nests	RP	Yes	EPE	RP and Chemo	Lung, liver mets. LR, DOD	<1
62	78	Small solid nests	NBx	No	–	RT and Chemo	NED	3

Note: AC-P indicates adenoid-cystic pattern; BCH, basal cell hyperplasia pattern; Chemo, chemotherapy; Enuc, enucleation; FU, follow-up; Loc, local recurrence; EPE, extra-prostatic extension; LR, local recurrence; MAR, margins; Mets, metastases; NA, not assessable; Nbx, needle biopsy; NED, no evidence of disease; OC, organ confined; RP, radical prostatectomy; RT, radiation; squamous, squamous metaplasia; SV, seminal vesicles; TUR, trans-urethal resection; DOD, died of disease.

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