Introduction
Majority of the prostatic carcinoma cases are acinar type adenocarcinoma. There are few rare histological subtypes of prostatic adenocarcinoma. One of them is foamy gland adenocarcinoma (FGC) which was first described by Epstein and Nelson in 1996.1 It is composed of cells with abundant xanthomatous cytoplasm and low N:C ratio. The features of classic acinar adenocarcinoma like large nuclei, prominent nucleoli and infiltrative pattern are not seen in most of the cases of foamy gland carcinoma. This variant can pose a diagnostic challenge as the low-grade nuclear features can resemble normal prostate glands especially in trans rectal ultrasound (TRUS) biopsies.
Case Report
A 70-year old male presented with increased frequency of micturition with dysuria in the past 1 month. Ultrasonography revealed a prostatic volume of 67 grams. Serum Prostate specific antigen (PSA) levels were 33.63 ng/ml. Per-rectal examination revealed a firm to hard prostate. A 12-core TRUS biopsy was performed. Per-rectal examination revealed a firm to hard prostate. Histopathological examination showed malignant cells forming acini and infiltrating the stroma (Figure 1). Individual cells had abundant foamy cytoplasm, pyknotic nucleus and inconspicuous nucleoli (Figure 2). Focal cells showed high grade nuclear features (Figure 3). Nine out of 12 cores sent were involved. The core involvement varied from 10–90% (overall 70% of core volume); and the Gleason Score was 4 + 4; Gleason grade group 4. Perineural involvement, lymphovascular emboli, extra prostatic extensions were not noted. Immunohistochemistry for Alpha methyl acyl coenzyme A Racemase (AMACR) was strongly positive (Figure 4).
We signed out the report as foamy cell variant of adenocarcinoma prostate. Our patient was advised radical prostatectomy but could not undergo surgery owing to his age and other co-morbidities.
Discussion
Foamy gland carcinoma (FGC) of prostate is a histological variant of adenocarcinoma prostate which is composed of cells with characteristic abundant foamy cytoplasm and low N:C ratio. The nuclear features of classic acinar adenocarcinoma and the infiltrative pattern are not seen in most of the cases of foamy gland carcinoma. Thus, warrants a careful clinicopathological correlation to not falsely categorize these cells with low grade nuclear features as normal prostate glands or as foamy macrophages seen in chronic prostatitis.
In literature the incidence of foamy gland carcinoma in TRUS biopsies is reported to be 17% to 22% while that in radical prostatectomy is between 13% to 22%.2, 3 Sevim B K et al from Turkey studied 251 TRUS-guided prostate biopsies out of which in 56 (22%) cases FGC was reported; 11 were pure FGC and 45 were mixed with conventional adenocarcinoma.2 The criteria used by them were presence of abundant foamy cytoplasm, pyknotic nuclei and infiltration. Warrick J et al reported 81 cases (17%) of FGC in 476 consecutive prostatic needle core biopsies.4 Only 2% (10 cases) showed pure foam gland carcinoma and had linear extent lesser than 10 mm. In a study by Hudson et al two case-series of non-consecutive radical prostatectomies were studied, and the incidence reported was 14.5% and 23%.5 Out of 110 prostate TRUS biopsies encountered in our institute in the past 3 years this was the first case of pure FGC. We have seen prostatic adenocarcinoma with small foci of FGC in 9 (8.2%) cases.
Some studies tried to evaluate parameters like age and S.PSA levels. Sevim B K et al has reported mean S.PSA levels of 46.5 ng/ml in FGC while mean levels in conventional adenocarcinoma were 31.2 ng/ml.2 However, the difference was not statistically significant. Hudson et al also made a similar observation.5
Initial reports of FGC were mostly low-grade malignancy as pyknotic nuclei mimicked benign prostatic glands and, in few cases, foamy macrophages; thus, posing a diagnostic difficulty in analyzing needle biopsies. Most cases had Gleason Score (GS) of 3 + 3. However, recent studies have shown high grade features in FGC and a higher GS. Zhao et al from Johns Hopkins, USA reported 55 cases of high-grade FGC (GS more than 7) with mean core involvement of 3.4 out of 12, 73% involvement and GS above 8 in 52% cases.6 In our case we reported in 9 cores GS as 4 + 4 with 70% involvement and focal presence of high-grade nuclear features.
Many studies have shown increased incidence of perineural invasion (PNI) in FGC.2 Our cases did not show any evidence of PNI or extra prostatic extension. Sevim B K et al has stated that higher incidence of PNI in FGC as compared to that in conventional adenocarcinoma has a significant contribution to the prognosis of disease.2
Warrick et al studied prostate needle biopsies over a 2-year period and performed immunohistochemistry (IHC).4 Out of 72 cases of FGC, 66 (92%) were positive (score 6 +) for AMACR and 30 (42%) were positive for ERG. Both showed uniform positivity. Tissues with weak AMACR were positive to ERG, however no AMACR negative case was ERG positive. Thus, ERG is an important marker in cases where AMACR positivity is weak. They concluded that FGC had a sensitivity to AMACR similar to that towards ERG. Our case showed a strong AMACR positivity.
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