Histologic and Histochemical Characterization of Seminal Vesicle Intraluminal Secretions.
In recent years, there has been a tremendous increase in the number of prostate needle biopsies, resulting in increased detection of prostate cancer and a rising number of radical prostatectomies. Thus, surgical pathologists are increasingly examining seminal vesicle material for pathologic examination. Furthermore, in some centers transrectal ultrasound-guided biopsies are specifically targeted at the seminal vesicles in an attempt to detect seminal vesicle involvement by prostate cancer. In our routine surgical pathology practice, one of us (M.B.A.) has anecdotally noted the presence of intraluminal seminal vesicle secretions in prostate needle biopsies, which assumed a morphology superficially resembling the well-characterized prostatic intraluminal crystalloids. Since prostatic crystalloids have been associated with neoplasia of prostate and constitute a useful diagnostic feature for this tumor,[1-7] misinterpretation of small acinar morphology of seminal vesicle epithelium with crystalloids as prostatic carcinoma may have diagnostic implications.
The presence of crystalloid morphology in seminal vesicles prompted us to investigate the light microscopic and histochemical characteristics of seminal vesicle secretions, which to our knowledge have not otherwise been studied in the pathology literature. The biochemical constitution of seminal vesicle secretions has been well characterized; these secretions are known to contain abundant fructose, citric acid, and other nutrient substances, as well as large quantities of prostaglandin and fibrinogen. The aim of the present study was to review a series of prostate needle biopsies, radical prostatectomies with prostatic adenocarcinoma, prostates from autopsy, and cystoprostatectomies without prostate carcinoma to investigate the light microscopic and histochemical characteristics of seminal vesicle secretions. Particular attention was paid to the crystalloid morphology of these secretions in order to identify distinguishing features from prostatic intraluminal crystalloids.
MATERIALS AND METHODS
A total of 253 prostate specimens, including 163 consecutive prostate needle biopsies, 75 radical prostatectomies performed for prostate cancer, 11 random autopsy cases, and 4 cystoprostatectomies without prostate cancer were retrospectively analyzed from the surgical pathology files of Henry Ford Hospital, Detroit, Mich. One case of prostate needle biopsy in which seminal vesicle epithelium contained crystalloids was retrieved from the consultation files of one of the authors (M.B.A.).
All types of specimens studied were fixed in 10% buffered formalin and processed in a uniform manner. Three step-sectioned levels of each needle biopsy and 2 to 7 (average 3) hematoxylin-eosin-stained sections of entire seminal vesicle were analyzed in each case from radical prostatectomies, autopsy cases, and cystoprostatectomies. Only prostate needle biopsies showing diagnostic morphologic criteria of seminal vesicle/ejaculatory duct were further analyzed for the present study. The following histologic criteria were used for the identification of seminal vesicle/ejaculatory duct epithelium: nuclei of the inner columnar cells showing frequently large, pleomorphic, and hyperchromatic nuclei ("monster nuclei"), often with intranuclear holes and intranuclear inclusions. The cytoplasm contained golden yellow pigment that was large, refractile, and chunky.
All cases of seminal vesicle were analyzed for the presence of intraluminal secretions. Based on our initial screening evaluation, intraluminal secretions were noted as being inspissated, dense, platelike; fluidlike; or having a crystalloid-like morphology. In each case with seminal vesicle epithelium, the secretions were evaluated for the following characteristics: location of secretion (central seminal ductal region vs peripheral tubuloalveolar glands) and predominant morphologic type (dense platelike, fluidlike, and crystalloid morphology). Secretions exhibiting crystalloid morphology were further analyzed for shape and size of crystalloids. Crystalloids were classified as scant when fewer than 3 were identified per low-power microscopic field (x10 objective, x10 ocular), moderate in number when 3 to 10 crystalloids were seen per low-power field, and numerous when more than 10 crystalloids were identified per low-power field.
Ten cases of seminal vesicles from radical prostatectomies and autopsy cases with representative forms of the different secretions identified by routine hematoxylin-eosin-stained slides were stained for periodic acid-Schiff (PAS) with and without diastase digestion, Alcian blue at pH 2.5, and mucicarmine histochemical stains using standard techniques.
The Fisher exact test was performed to determine the statistical significance of the association of crystalloids in 2 groups, those with and without prostatic carcinoma.
Of 163 prostate needle biopsies reviewed, 9 had morphologically diagnostic seminal vesicle/ejaculatory duct epithelium, accounting for an incidence of 5.52% in consecutively sampled prostate biopsies. Secretions were present in 81 (82%) of 99 seminal vesicles as follows: 4 (44%) of 9 needle biopsies with seminal vesicle/ejaculatory duct epithelium, 68 (90%) of 75 radical prostatectomies, and 9 (82%) of 11 prostates without carcinoma, including 7 of 11 autopsy cases and 4 of 4 cystoprostatectomy cases. Seminal vesicle intraluminal secretions had the following morphologic features: 49 (61%) of the 81 cases with secretions showed predominantly dense, eosinophilic, platelike, inspissated secretions; 12 (15%) had predominantly fluidlike eosinophilic to slightly basophilic secretions, often filling the entire lumen; and 20 (24%) showed varying amounts of intraluminal crystalloids (Table 1). Combination of more than 1 type of secretion was frequently seen. Twelve (15%) of 81 cases had combined secretions in addition to the predominant form. There were no cases in which crystalloids were associated with predominant fluidlike secretions. Sixty-three percent of cases had secretions predominantly in peripheral tubuloalveolar glands, and 37% had secretions predominantly in the central large ductal structure.
Table 1. Morphologic Features of Seminal Vesicle Secretions
Histologic Appearance No. (%) Fluidlike secretion 12(*) (15) Dense platelike secretion 49(*) (61) Crystalloid morphology 20 (24) Total 81 ([dagger]) (100)
(*) Numbers reflect seminal vesicles in which the secretion form was the predominant one.
([dagger]) Of 99 seminal vesicles, 81 had intraluminal secretions.
The crystalloids were invariably moderate to numerous (92%), averaging 6 to 7 crystalloids within a lumen and at times forming large clusters filling the entire acinus (Figures 1 and 2). Their greatest cross-sectional dimension ranged from 4 to 80 [micro]m. The crystalloid morphology was most commonly associated with inspissated, dense, platelike secretions (71%) and appeared to be created by fracturing of the platelike secretions. Often the fractured platelike secretions and crystalloid forms were associated with refractile spherical particulate debris (Figure 2 and 3). The crystalloids varied in shape, including elliptical, ovoid, rodlike, cylindrical, and occasionally rectangular forms. A majority of the crystals exhibited curved edges and blunt angles. However, a few crystalloids with sharp angles and parallel sides (approximately 4%), similar to the characteristics of prostatic crystalloids, were also present, although usually in conjunction with other polymorphic shapes. Eighteen patients (24%) with prostate carcinoma and 6 patients (25%) without prostate carcinoma had seminal vesicle secretions with crystalloid morphology (P = 1.0000) (Table 2). Fluidlike secretions (Figure 4) reacted positively with PAS (with and without diastase) (Figure 5), Alcian blue at pH 2.5, and mucicarmine, suggesting acid mucopolysaccharide content. Eosinophilic, dense, platelike secretions and secretions with crystalloid morphology stained positively with PAS (with and without diastase) but were negative for Alcian blue at pH 2.5 (Figure 6) and mucicarmine, suggesting loss of acidity of secretions (Table 3).
[Figure 1-6 ILLUSTRATION OMITTED]
Table 2. Distribution of Cases With Crystalloid Morphology(*)
No. (%) With No. of Cases Crystalloids Benign 24 6 (25) Adenocarcinoma 75 18 (24) Total 99 24 (24)
(*) The association of crystalloid morphology in benign and malignant prostate glands is not statistically different (P = 1.000).
[TABULAR DATA 3 NOT REPRODUCIBLE IN ASCII]
Although biochemically well characterized, seminal vesicle secretions as apparent by light microscopy to our knowledge have not been previously described in detail in the histology or pathology literature. In our study, we found intraluminal seminal vesicle secretions to be very common (82%), and they exhibited variable morphologic appearances. Dense platelike secretions were the most common (61%) and appeared to represent inspissated secretions, which were visible as densely eosinophilic structures with curved or sharp angles, occasionally with fracturing. Fluidlike eosinophilic to occasionally basophilic secretions were less common, seen in 15% of cases as the predominant form of secretions, and in contrast to dense platelike secretions are histochemically acid mucopolysaccharide in nature (positive for Alcian blue [pH 2.5] and mucicarmine). Inspissated platelike secretions differ morphologically from prostatic corpora amylacea, which are round to oval with concentric lamellations,[11,12] by their more haphazard shape (rectangular, rhomboid, ovoid) and lack of lamellations.
The most interesting aspect of these secretions (from the surgical pathologists' perspective) is the crystalloid morphology of secretions. Seen in 24% of seminal vesicles, these crystalloid forms are most often associated with dense platelike secretions and appear to be created as a result of fracturing of inspissated secretions. Similar histochemical reactions in the dense platelike secretions and crystalloid morphology confirm our morphologic observation, and we speculate that the loss of acidity of secretions (compared to fluidlike secretions, which are acidic) provides a trigger for inspissation and subsequent crystallization.
The crystalloid structures on occasion closely resembled or were remarkably similar to prostate crystalloids. Distinction of seminal vesicle crystalloids from prostatic crystalloids has diagnostic implications. In 1977, Holmes reported the association of prostatic crystalloids with adenocarcinoma, particularly well-differentiated and moderately differentiated tumors. Subsequent researchers confirmed this association, and the finding of intraluminal crystalloids within prostatic acini constitutes a useful but not absolute diagnostic clue for prostatic carcinoma.[4-6] Intraprostatic crystalloids may be noted in benign glands adjacent to carcinoma or may be present in benign acini in prostatic biopsies negative for carcinoma.[1,2,4,12] Follow-up of patients with the latter finding has shown no subsequent increase in detection of prostate cancer in repeat biopsies.[2,12] Prostatic intraluminal crystalloids are orangeophilic to eosinophilic and refractile in hematoxylin-eosin-stained sections.[2,3,5,11] Their shape may vary considerably, forming rods, rhombi, and needlelike, prismatic, hexagonal, and platelike configurations ranging from 7 to 80 [micro]m.[3,5,11] The crystalloids are characteristically present singly or occasionally in small clusters (average 1-2 per lumen) and typically have sharp angles and parallel sides.[3,5,11] They are seldom associated with corpora amylacea. Seminal vesicle intraluminal crystalloids show several differing features: they are invariably multiple (92%), averaging 6 to 7 crystalloids per lumen; are frequently curved or have blunt angles and edges; and are associated with fracturing within dense inspissated secretions (71%). The contrasting features between intraluminal seminal vesicle and prostatic crystalloids are summarized in Table 4. Crystalloid morphology resembling that in prostatic acini has also been observed in association with benign and malignant tumors of the salivary gland and ovary and with breast carcinoma.
[TABULAR DATA 4 NOT REPRODUCIBLE IN ASCII]
In our study, we found no relationship between seminal vesicle crystalloids and associated malignancy in the prostate gland. Similar to the incidence of 5% sampling of seminal vesicle-type epithelium in prostate needle biopsies reported by Coyne et al, we found an incidence of 5.2% in our analysis of consecutive prostate biopsies. It is well known that seminal vesicle/ejaculatory duct epithelium constitutes an important histoanatomic structure that may be potentially confused with prostatic small acinar carcinoma.[9,10] Both prostatic and seminal vesicle epithelia frequently contain pigment, although it is more consistently coarse, refractile, present throughout the epithelium, and golden yellow in the latter and usually fine, focal, inconspicuous, predominantly basal in location, and yellow, yellow-brown, or blue in the former. Awareness of crystalloid morphology in seminal vesicle epithelium and the features distinguishing this morphology from prostatic intraluminal crystalloids may be important because seminal vesicle epithelium with a small acinar morphology, accompanying cytologic atypia, and crystalloid morphology may raise the question of adenocarcinoma.
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Accepted for July 26, 2000.
From the Departments of Pathology, St John Hospital, Detroit, Mich (Drs Shah and Giraldo); Henry Ford Hospital, Detroit, Mich (Dr Lee); and Emor University Hospital, Atlanta, Ga (Dr Amin).
Reprints: Mahul B. amin, Md, Department of Pathology, emory University Hospital, 1364 Clifton Rd NE, Atlanta, GA 30322.