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Genitourinary Pathology
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Case 4 -
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Ordinary and Florid BCH (Patterns 1 and 2) and Basal Cell Carcinoma (Pattern 3) with Focal Areas Resembling BCH
Rodolfo Montironi
Polytechnic University of the Marche Region
Ancona, Italy
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Click on each slide thumbnail image for an enlarged view
Abstract
Prostatic basal cell proliferations range from ordinary basal cell hyperplasia (BCH) to florid basal
cell hyperplasia to basal cell carcinoma. The separation between these forms of BCH, including the
variant with prominent nucleoli (formerly called atypical BCH), from basal cell carcinoma depends on
morphological and immunohistochemical criteria, and, in particular, on the degree of cell proliferation.
In florid BCH the proliferation index is intermediate between ordinary BCH and basal cell carcinoma.
Immunohistochemistry is also useful in the identification of the cell composition of the basal cell
proliferations, which includes the basal cell nature of the cells, their myo-epithelial differentiation,
and c-erbB-2 onco-protein expression . Based on the information derived from the literature and on the
appearance and follow-up of the case presented here, florid BCH might represent a lesion with an
intermediate position between ordinary BCH and basal cell carcinoma. However, criteria useful for the
identification of those cases with a true precursor nature are not available. Basal cell carcinoma is in
general seen as a low grade carcinoma. The immunohistochemical expression of c-erbB-2 onco-protein,
similar to that seen in breast cancer, might have a therapeutic importance.
Case 4 - Figure 1 - Epithelial cell nests and islands arranged in basophilic nodules having expansible growth margins.
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Case 4 - Figure 2 - Eccentric thickening of the basal cell layer.
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Case 4 - Figure 3 - Epithelial cell nests and islands. Single lumina are present.
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Case 4 - Figure 4 - Solid epithelial cell nests and cords. The peripheral palisading pattern is evident. Small globules of dense eosinophilic material surrounded by basaloid cells are seen in some nests.
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Case 4 - Figure 5 - Nest punctuated by cribriform spaces filled with tenuous basophilic mucinous secretion; squamous differentiation is seen in the lower left corner.
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Case 4 - Figure 6 - Cells with optically clear cytoplasm
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Introduction
Basal cell proliferations in the prostate gland exhibit a morphologic continuum ranging from basal
cell hyperplasia in the setting of nodular hyperplasia to malignant basal cell lesions that resemble, to
a certain degree, basal cell carcinoma of the skin and adenoid cystic carcinoma of the salivary gland
[2,
3].
A large number of terms have been used for these neoplasms and related growths.
The aim of this paper, which includes a case presentation and discussion, is to review the
morphologic spectrum and the immunohistochemical findings of the basal cell proliferations in the
prostate.
Case History
- A
71-year-old Caucasian man presented in September 1992 with a 1-year history of increasing urinary
obstructive symptoms. Diffuse enlargement of the prostate was documented by transrectal ultrasound and
digital rectal examination. Supra-pubic (simple) prostatectomy was performed.
The preoperative total serum PSA was 2.5 ng/ml. After the operation PSA decreased to below 1.0 ng/ml.
The diagnosis was benign prostatic hyperplasia associated with diffuse basal cell hyperplasia.
- The patient was clinically well until 1996
when he presented with recurrent urinary obstructive symptoms. Transurethral resection of the prostate
(TURP) was performed in June 1996, and normal voiding was achieved. The pathology report included basal
cell carcinoma of the prostate vs. urothelial carcinoma. The reporting
pathologist favored the latter diagnosis.
- In March 1997, the patient underwent a second TURP, and
permanent normal voiding was achieved. The pathology report, which included revision of the previous two
reports, was basal cell carcinoma with extension to the extraprostatic tissue.
- Local recurrence was documented in 2000. This was a
progressively growing mass (20 cm across) originating from the prostate and compressing and obstructing
the rectum. There were no urinary voiding problems. The patient was not given any therapy (i.e.,
chemotherapy or radiotherapy). A computed tomography scan performed in 2003 did not reveal secondary
deposits in lymph node and distant parenchyma. The PSA remained below 1.0 ng/ml. He died from unrelated
hearth failure in mid-2003. An autopsy was not done.
Gross and Microscopic Pathology
Supra-pubic prostatectomy specimen (examined in 1992)
The surgical specimen weighted 60 grams and measured 6 by 5 by 4 (volume calculated on the basis of
the ellipsoid volume formula: 62 cc). The cut surface was white and nodular. Ten tissue blocks were
randomly taken and processed. Ten percent of the specimen showed the appearance of benign prostatic
hyperplasia (BPH). The remaining 90% showed diffuse alteration of the prostatic architecture and
structure by a composite nodular lesion (Figure 1.A) with three distinct patterns (Figures 1B-1P; Table
1).
Table 1. Antibodies and immunostaining results
| Antibodies | Cells in close contact with the stroma | Cells located in the center of the nests | Cells in-between |
| 34betaE12 | positive | negative | positive |
| p63 | positive | negative | positive |
| bcl-2 | positive | negative | positive |
| CK20 | negative | negative | negative |
| alpha-smooth muscle actin | positive (focal) | negative | negative |
| S-100 protein | positive (focal) | negative | negative |
| AE1/AE3 | negative | positive | negative |
| CK7 | negative | positive | negative |
| PSA | negative | positive (focal) | negative |
| Ki-67 | positive (focal) | negative | positive |
| laminin | positive | negative | negative |
| c-erbB-2 onco-protein | negative | positive | positive |
| chromogranin | negative | negative | negative |
Pattern 1: Tightly packed small acini arranged in a lobular configuration with sharp peripheral
borders. The acini, far smaller than the unaffected normal-looking ducts and acini, showed symmetrical
circumferential thickening of the basal cell layer, usually two or more cell layer thick, surrounding a
continuous layer of cuboidal-to-columnar luminal cells. The nuclei were small to medium-sized, elongate
or round, with uniform pale chromatin that was occasionally vesicular. Nucleoli were inconspicuous or
absent. The cytoplasm was difficult to identify by light microscopy and appeared as a dark, narrow rim
with inconspicuous cell margins. Occasionally the thickening was eccentric and composed of small solid
nests of polygonal cells with the nuclear appearance of those seen in the ducts with symmetric
proliferation of the basal cells (Figure 1.B). All cells stained positively for keratin 34betaE12, p63,
and bcl-2. The cells were negative for CK7, CK20, AE1/AE3, PSA, and chromogranin. Mitotic figures were
rare, and 11% of the cells were Ki-67 positive. The borders between the basal and the luminal cells were
usually sharp. The latter showed more abundant cytoplasm with a slightly basophilic appearance, easily
identifiable cell membrane, and nuclei with open chromatin and occasional small nucleoli. The luminal
cells were negative for keratin 34betaE12, p63, CK20, and bcl-2 and positive for AE1/AE3 and CK7. There
were no mitotic figures, and no Ki-67 positive nuclei were seen. Two percent of the luminal cells were
PSA positive. This occupied approximately 60% of the specimen. In the tissue sections there was a
homogeneous distribution of the lobules with these features, giving the impression that such lobules had
replaced the epithelial nodules usually seen in BPH.
Pattern 2. This pattern consisted of epithelial cell nests and islands arranged in nodules ranging up
to 1 cm in diameter and having expansible growth margins (Figure 1.A and 1.C). There was often a
distinct outer layer of palisading basal cells surrounding larger, polygonal epithelial cells that formed
the main bulk of the nests. The basal cell cells contained minimal cytoplasm and an oval to round nuclei
with stripped chromatin, sometimes hyper-chromatic, and an occasional small solitary nucleoli. The large
polygonal cells contained more eosinophilic cytoplasm, which was more abundant in the center of the
nests, with slightly larger nuclei and one to two distinct nucleoli. The immunohistochemical results
were similar to those seen in the pattern 1. All cells stained for keratin 34betaE12, p63 (Figure 1.I),
and bcl-2. The cells were negative for CK7, CK20 AE1/AE3 and chromogranin. Mitotic figures were rare
and only seen in the areas of polygonal cells; 18% of the cells were Ki-67 positive (Figure 1.L). Most
of the nests were solid. Central or eccentric single lumina were present in a minority of nests. Cells
lining the lumina were either cuboidal or tall, and AE1/AE3 and CK7 positive (Figure 1.K). Some of the
lumina contained both alcian-blue-positive acid mucin and PAS-positive neutral mucin; intra-cytoplasmic
mucin was not observed. PSA immunostaining was negative. This pattern occupied approximately 20% of the
specimen. Some lobules with pattern 1 contained small foci of pattern 2.
Pattern 3. This pattern consisted of poorly circumscribed nodular collections of epithelial cell nests
and cords, most solid, but some containing single lumina (Figures 1.D, 1.E, 1.F, 1.G, and 1.H). Compared
with pattern 2, the nests and cords were larger, more uniform in size, and separated by a variable amount
of fibro-myxoid stroma. Small nodules or globules of dense eosinophilic material surrounded by basal
cells were seen in some nests towards the periphery and in close proximity to the stroma (Figure 1.D).
The cell composition was similar to that present in the pattern 2. However, the peripheral palisading
pattern was more evident, and the polygonal cells had nuclei two to three times larger with considerable
irregularity and variable size. Chromatin was finely dispersed with rare, small nucleoli. The
immunohistochemical results were similar to those seen in patterns 1 and 2. All the cells stained for
keratin 34betaE12, p63, and bcl-2. The cells were negative for CK7, CK20, AE1/AE3, and chromogranin.
Mitotic figures were more frequent than in the other two patterns and always seen in relation to the
areas of polygonal cells; 35% of the cells were Ki-67 positive (Figure 1.M). The cells lining the lumina
were basal, AE1/AE3 and CK7 positive, and PSA negative. Pattern 3 occupied approximately 10% of the
specimen. In some areas, it was adjacent to and in continuity with foci with pattern 2.
Additional immunohistochemical and morphometric results:
- Cells stained with antibodies to alpha-smooth muscle actin
(Figure 1.J) and S-100 protein were seen in all three patterns. The positive cells were located in the
cell layer adjacent to the stroma, including those with a palisading feature. All other cells were
negative. The proportion of positive cells was greatest in pattern 2, lowest in pattern 3, and
intermediate in pattern 1 (alpha-smooth muscle actin: 7%, 4% and 2%, respectively; S-100 protein: 5%,
3% and 1%, respectively).
- Cells
stained with the antibody to c-erbB-2 onco-protein were present in all three patterns, mostly in the
polygonal cells in patterns 2 and 3 (close to 40%) and luminal cells of pattern 1 (more than 50%)
(Figures 1.O and 1.P). The cell layer adjacent to the stroma was usually negative.
- Morphometric analysis showed that the nuclear
and nucleolar area (expressed in sq. μm) increased from ordinary BCH (mean and SD of the nuclear
area: 27.95 and 6.77; mean and SD of the nucleolar area: 0.94 and 0.19) to florid BCH (mean and SD of
the nuclear area: 38.61 and 6.23; mean and SD of the nucleolar area: 1.55 and 0.52) to basal cell
carcinoma (mean and SD of the nuclear area: 53.52 and 10.37; mean and SD of the nucleolar area: 1.72
and 0.34); the values in the basal cells of unaffected duct and acini were lower (mean and SD of the
nuclear area: 22.19 mm and 7.29; mean and SD of the nucleolar area: 0.91 and 0.45). The differences
for the nuclear and nucleolar area (Kruskal-Wallis test) were statistically significant at the level of p
< 0.001 and p = 0.022, respectively.
First transurethral resection specimen (examined in 1996)
The total weight of the chips was 35 grams. Most of the material was examined histologically. Twenty
percent of the tissue was normal prostate. Ten percent was occupied by pattern 2, and seventy percent by
pattern 3. Very few chips showed nests and islands punctuated by cribriform spaces filled with basophilic
mucinous secretion; nests with squamous differentiation; cells with optically clear cytoplasm; and
isolated foci with the appearance of pattern 1, the differences being in the fact that the nuclei were as
large as in the pattern 3 described above and the degree of proliferation, i.e., Ki-67-postive cells, was
as high as 40%. In addition, the lesion showed extension out of the prostate into periprostatic adipose
tissue and perineural invasion.
Second transurethral resection specimen (examined in 1997)
Ten grams of prostatic chippings were received and processed for paraffin sections. Histologically
100% of tissue was occupied by poorly circumscribed nodular collections of cell nests of pattern 3.
Diagnosis
Ordinary and Florid BCH (Patterns 1 and 2) and Basal Cell Carcinoma (Pattern 3) with Focal Areas Resembling BCH
Discussion
Morphology
A spectrum of basal cell proliferations ranging from hyperplasia to carcinoma exists in the prostate
[12]
(Table 2). These are usually located in the transition zone.
Table 2. Basal cell proliferations of the prostate: diagnostic criteria together
with major immunohistochemical findings (see text for the full range of features)
| | Architecture | Cytology | 34betaE12 and p63 | Prostate-specific antigen | S-100 protein and alpha-smooth muscle actin |
| Normal basal cell layer | Near-continuous single cell layer | Small elongate cells, ovoid nuclei, scant cytoplasm | + | - | - |
| Ordinary BCH (including basal cell adenoma and adenomatosis) | Small cell nests, two cell layer minimum, solid or cystic | Small to medium size nuclei, inconspicuous nucleoli, cytoplasm difficult to identify | + | -/+* | +/-* |
| Florid BCH | Compact glandular proliferation with solid nests | Cells with moderately enlarged nuclei, often with a prominent nucleolus | + | -/+ | +/- |
| BCH with prominent nucleoli (or atypical BCH) | Same as ordinary BCH | Nucleoli similar to those seen in acinar adenocarcinoma | + | -/+ | +/- |
| Basal cell carcinoma (adenoid cystic carcinoma) | Islands and cords of cells with peripheral palisading or nests of cells with an adenoid cystic pattern | Basaloid cells with large nuclei with considerable irregularity and variable size | + | -/+ | - |
* See also Table 1 for cell location
Ordinary (Usual, typical or classical) basal cell hyperplasia consists
of numerous small to normal-sized, round basophilic acini with several layers of basal cells (glandular
architectural type) or solid nests either arranged in a lobular configuration or seldom "infiltrating"
the stroma (see below) (Figure 1B). The morphology corresponds to our pattern 1. None of the cases of
ordinary BCH, by definition, contains either prominent nucleoli (their mean diameter is less than 1
μm)
[2] or polymorphism; however, rare cases may show the presence of hyper-chromatic nuclei,
enlarged nuclei, and rare mitotic figures. BCH resembles prostate acini seen in the fetus, accounting
for the synonyms "fetalization" and "embryonal hyperplasia". BCH may be composed of basal cell nests
with areas of luminal differentiation resembling similar lesions of the salivary gland. This is denoted
as the adenoid basal form of BCH.
Basal cell adenoma is identical to ordinary BCH, although the
proliferating basal cell masses are usually large and circumscribed, with nodular or adenoma-like
pattern. In contrast to basal cell carcinoma, basal cell adenoma is well circumscribed, lack necrosis,
and the stroma between the basal cell nests is similar to that of the surrounding normal prostatic
stroma. Occasionally, BCH is multifocal (adenomatosis). The terms basal
cell adenoma and adenomatosis are very rarely used.
Four morphologic findings of BCH have been reviewed in a recent paper [11]: intra-cytoplasmic
globules (these stain for alpha-fetoprotein and alpha-1 antitrypsin), calcifications, squamous features,
and cribriform (Table 3). Recognition of intra-cytoplasmic globules can help to identify a lesion as
that of BCH. This feature, reported also by Yang et al [14], has not been seen in other prostatic
lesions. Intra-luminal calcifications can also aid in the recognition of BCH, given their rarity in
other prostatic conditions. Knowledge that squamous and cribriform findings of BCH exist and awareness
of their light microscopic and immunohistochemical features can help to distinguish these lesions from
preneoplastic and neoplastic diseases of the prostate.
Table 3. Basal cell proliferations of the prostate: unusual morphologic findings
(BCH stands for basal cell hyperplasia)
- Intra-cytoplasmic globules
- Calcifications
- Squamous features
- Cribriform features
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BCH may have a florid appearance (i.e., florid basal cell hyperplasia).
Our pattern 2 is identical to this and corresponds to the description given by Van de Voorde et al [13]:
compact glandular proliferation with solid nests; the cytology in some areas looks disturbing because the
cells have a moderately enlarged nucleus, often with a prominent nucleolus; a few mitotic figures are
present; the intervening stroma is scant and cellular; the lesions is not well circumscribed and are
intermingled with the surrounding glands, giving the impression of "infiltration" (this is also called
diffuse type) (Figure 1.C). Yang et al gave an additional criterion for the identification of florid
BCH: extensive proliferation of basal cells involving more than 100 small crowded acini (per section)
forming a nodule [14].
BCH may have prominent nucleoli (i.e., basal cell hyperplasia with prominent
nucleoli), but is otherwise identical to ordinary BCH. The nucleoli are round to oval and lightly
eosinophilic, similar to those seen in acinar adenocarcinoma of the prostate (their mean diameter is 1.96
μm)
[2]. There is chronic inflammation in most cases, suggesting that nucleolomegaly is a
reflection of reactive atypia [2]. These cases are also referred to as atypical
basal cell hyperplasia
[2,
3].
BCH with prominent nucleoli may be mistaken for high-grade prostatic intraepithelial neoplasia (PIN).
Although occasionally the distinction between these two entities may be difficult, usually they are
distinct. The nuclei in BCH tend to be round whereas, at times, the cells form small solid basal cell
nests. In contrast, the cells in PIN tend to be more pseudo-stratified and columnar and do not occlude
the glandular lumina. Within areas of BCH, atypical looking basal cells can be seen underling the
overlying benign appearing secretory cells. PIN has full thickness cytological atypia with the nuclei
oriented perpendicular to the basement membrane. The use of antibody against either 34betaE12 or p63 can
help in difficult cases. In BCH immunohistochemistry shows multilayered staining of the basal cells,
whereas an interrupted immuno-reactive basal cell layer is seen in PIN. Yang et al [15] showed that
immunostaining for alpha-methylacyl-coenzyme racemase (i.e., P504S) is negative in florid BCH and
positive in high grade PIN and adenocarcinoma. Immunostaining for glutathione-s-transferase pi (GST-pi)
is positive in florid BCH and negative in adenocarcinoma. The same group of authors performed
ultra-structural analysis to further document the basal cell features of florid BCH.
BCH, mainly with a glandular architecture or when florid, may be confused with adenocarcinoma (Table
4). BCH can be distinguished from adenocarcinoma by its very basal cell appearance. The glands appear
basophilic at low power due to multilayering of basal cells which have scant cytoplasm. In contrast,
gland-forming adenocarcinoma of the prostate almost always has more abundant cytoplasm resulting in a
more eosinophilic appearance to the glands. If by light microscopy there is difficulty in distinguishing
BCH from prostatic adenocarcinoma, utilization of immunohistochemistry with basal cell specific
antibodies (34betaE12 or p63) can differentiate between these two
lesions [5].
Table 4. Basal cell hyperplasia (ordinary, florid and with nucleoli): differential
diagnoses. Morphologic criteria together with major immunohistochemical findings (see text for the full
range of features)
| | Architecture | Cytology | 34betaE12 and p63 | Prostate-specific antigen | S-100 protein and alpha-smooth muscle actin |
| BCH (Ordinary, florid and with nucleoli) | Cell nests, two cell layer minimum, solid or cystic | Small to medium size nuclei, nucleoli may be prominent in some forms | + | -/+ | - to +/- |
| High-grade PIN | Ducts and acini with various architectural patterns, ranging from flat to cribriform | Cells with enlarged nuclei, with a prominent nucleolus, similar to those in adenocarcinoma | +/-
(basal cells) | + | - |
| Adenocarcinoma | Acini of various sizes, either separated or fused, with different architectural patterns, such as flat or mono-layered or cribriform | Cells with enlarged nuclei, with prominent nucleoli | - | + | - |
| Sclerosing adenosis | Acinar structures, predominantly small, lined by bi-layered epithelium | Small to medium size nuclei, inconspicuous nucleoli | +
(basal cells) | + | + |
| Benign seminal vesicle/ejaculatory duct epithelium | Ducts lined by a bi-layered epithelium | Prominent nuclear atypia and pleomorphism | + | - | - |
| Squamous metaplasia | Ducts and acini lined by multilayered epithelium similar to epidermis | Cells with small to medium size nuclei, inconspicuous nucleoli; keratinization often prominent | + | - | - |
| Transitional cell metaplasia | Ducts and acini lined by multilayered epithelium similar to urothelium | Small to medium size nuclei, inconspicuous nucleoli; luminal cells larger than those in the intermediate and basal layers | + | - to +/-
(scattered luminal cells) | - |
Basal cell carcinoma (basal cell carcinoma/adenoid cystic carcinoma) is
characterized by proliferation of cells arranged in various architectural patterns. Two morphological
variants of basal cell carcinomas can be recognized in the prostate. Islands and cords of epithelial
cells with peripheral palisading characterize the first type, morphologically similar to basal cell
carcinoma of the skin. The second type, also called adenoid cystic carcinoma, is composed of nests of
infiltrating tumor cells with an adenoid cystic pattern, morphologically similar to the adenoid cystic
carcinoma of the salivary glands. The case presented here, with its pattern 3, belongs to the first
variant, even though few areas with the second are observed (Figures 1.D and 1.E). Focal squamous
differentiation and clear cell appearance are seen (Figures 1.E and 1.F)
The diagnostic criteria for malignancy in basal cell carcinoma include: (a) extensive infiltration
between normal prostate glands, (b) extension out of the prostate, (c) perineural invasion, or (d)
necrosis (Table 5)
[2,
3,
6].
The most obvious criterion of malignancy observed in the current case was
the extension out of the prostate (Figure 1.G). Perineural invasion was also seen (Figure 1.H). Our
case showed the presence of focal areas of basal cell carcinoma mimicking the classical BCH.
Table 5. Basal cell carcinoma: diagnostic criteria for
malignancy
- Extensive infiltration between normal prostate glands
- Extension out of the prostate
- Perineural invasion
- Necrosis
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The differential diagnosis of basal cell carcinoma includes poorly differentiated (mostly Gleason's
grade 5) adenocarcinoma (basal cell carcinoma may occur, rarely, in combination with conventional
adenocarcinoma) and urothelial carcinoma (Table 6). Poorly differentiated adenocarcinoma may growth in
solid nests and, similarly to basal cell carcinoma, is not reactive for PSA. Lack of immuno-reactivity
for p63 and 34betaE12, however, is helpful in recognizing conventional adenocarcinoma, though it has been
reported that this tumor may occasionally express p63. Similarly to basal cell carcinoma, urothelial
carcinoma may exhibit a solid growth pattern with peripheral palisading and central necrosis and may
express high level of p63. However, urothelial carcinoma expresses CK20 and CK7. Basal cell carcinoma
is positive for CK7 and negative for CK20 [8].
Table 6. Basal cell carcinoma: differential diagnoses. Morphologic criteria
together with major immunohistochemical findings (see text for the full range of features)
| | Architecture | Cytology | 34betaE12 and p63 | Prostate-specific antigen | S-100 protein and alpha-smooth muscle actin |
| Basal cell carcinoma (adenoid cystic carcinoma) | Proliferation of cells arranged in various architectural patterns, showing morphologic criteria for malignancy (see Table 5) | Basaloid cells with large nuclei with considerable irregularity and variable size | + | -/+ | - |
| Poorly differentiated adenocarcinoma (mostly Gleason grade 5) | Tumor proliferation without glandular differentiation and composed of solid sheets, cords or single cells; necrosis can be present | Cells with enlarged nuclei and prominent nucleoli | - | + | - |
| Transitional cell (urothelial) carcinoma | Irregular solid nests and cords with a striking propensity for growth within ducts and acini | High nuclear grade with substantial nucleomegaly, nuclear pleomorphism, and nuclear hyperchromasia. Prominent nucleoli often present. | + | - | - |
| Neuroendocrine carcinoma | Sheets of cells, with ribbons, nesting, palisading along fibrous bands, and rosette-like structures | Polygonal, round, or spindled tumor cells with scanty cytoplasm, hyperchromatic nuclei identical to pulmonary small cell carcinoma | - | - | - |
| Basaloid carcinoma of the rectum | Solid tumor nests exhibiting peripheral palisading, sometimes with foci of mucin secretion and area of squamous differentiation | Similar to cutaneous basal cell carcinoma | + | - | - |
Immunohistochemistry
The results of the immunohistochemical investigations published by different groups and the analysis
of our case have pointed out the following four features (Table 7).
Table 7. Basal cell proliferations of the prostate: immunohistochemistry
- Nature of the cells involved in the basal cell proliferations
- Cell composition: myo-epithelial cells, proliferating cells, and luminal cells
- Markers usually seen in neoplasias of other sites and organs: laminin and c-erbB-2 onco-protein
- Chromogranin positive cells (neuroendocrine differentiation)
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The first is related to the nature of the cells involved in the basal cell proliferations.
Immunohistochemistry clearly indicates that they have the same immuno-phenotype of the basal cells
present in normal ducts and acini. The cells are positively and strongly stained with 34betaE12 and p63
(Figure 1.I). These are the two consolidated markers for the basal cells in the prostate, as seen also
in our case, and their absence is in favor of prostate adenocarcinoma [5].
The second concerns cell composition. Our investigation points out that there might be at least three
types of cells: (a) cells with a palisading aspect in close contact with the stroma, (b) cells in the
center of the nests where lumina are seldom seen, and (c) cells in-between these two types. McEntee et
al were the first to document the heterogeneous cell composition in prostatic BCH and neoplasia in their
comparative pathology study in human and non-human primates [9].
The cells in contact with the stroma show focal positivity for S-100 and alpha-smooth muscle actin
(Figure 1.J). The expression of these two markers indicates that myo-epithelial differentiation appears
in the basal cell proliferations, as usually takes places in sclerosing adenosis, whereas it is absent in
normal prostate. This type of differentiation was mentioned both in benign and malignant basal cell
lesions in at least two previous publications
[13,
14].
The exact location of the myo-epithelial cells
was documented by Yang et al [15]. Grignon et al observed the presence of S-100 positivity in absence of
reactivity with muscle-specific actin [4]. They concluded that S-100 positivity alone does not
necessarily indicate myo-epithelial cell differentiation.
The cells that are located in the center of the nests and those lining the small lumina stain
positively with AE1/AE3 (Figure 1.K), whereas the cells in the other two locations are negative. The
same cells are 34betaE12 and p63 negative [3] and only rarely express a faint positivity for PSA. The
basal cells in the normal ducts and acini do not stain with AE1/AE3, whereas all the cells present in
ducts and acini with atrophic features are intensely stained. Such findings indicate that the cells
present in the basal cell proliferations show some degree of differentiation towards the secretory cell
phenotype.
Mitoses and Ki-67 positivity ((Figures 1.L and 1.M) are mainly seen in the nuclei that in the nests
occupy an intermediate spatial position between the peripherally and centrally located cells. This
indicates that the cells in such location belong to a kind of proliferative compartment, whereas the
cells in contact with the stroma and those in the center represent the differentiative/differentiated
compartment [13].
The third interesting feature is that the basal cell proliferations express two markers usually seen
in neoplasias of other sites and organs. The first is the demonstration of laminin both in the stroma
surrounding the cell nests and in small eosinophilic globules surrounded by the cells (Figure 1.N). This
feature is usually seen in tumors of the salivary glands. The other is represented by the expression of
c-erbB-2 onco-protein, similar to that seen in breast cancer (Figures 1.O and 1.P).
The forth is represented by the presence of a small proportion of cells with neuroendocrine
differentiation, as documented by chromogranin immunostaining [14]. This was not seen in our case.
Differential diagnosis between basal cell hyperplasia and basal cell
carcinoma
In contrast with BCH, basal cell carcinoma appears infiltrative rather than lobulated, with invasion
around nerves, or into soft tissues, and with necrosis. Proliferation (assessed by Ki-67 immunostaining)
is also helpful in distinguishing basal cell carcinoma from the other basal cell proliferations. The
proliferation index in basal cell carcinoma is greater than in the ordinary BCH, the values in florid BCH
and BCH with prominent nucleoli being intermediate between ordinary BCH and basal cell carcinoma [14].
Proliferation in areas of basal cell carcinoma with the pattern mimicking BCH is as high as in the
classical nested type of basal cell carcinoma [13].
Morphology and immunohistochemistry suggest that florid BCH has an intermediate position between
ordinary BCH and basal cell carcinoma. The exact position of BCH with nucleoli is not entirely clear.
There is a lack of clinical information in the very few studies with the follow-up of the patients.
However, it shows morphologic features of both ordinary and florid BCH.
Relationship between basal cell hyperplasia and basal cell carcinoma
The clinical presentation and history of the case included in this investigation gives support to the
view expressed by Reed [10] according to which BCH is a preneoplastic lesion. In particular, florid BCH
could derive from ordinary BCH and could be the direct precursor of basal cell carcinoma. This view is
also supported by the observation made by some authors on the occurrence of extensive BCH in the prostate
with basal cell carcinoma
[1,
2,
3,
4,
8]
Natural history of basal cell carcinoma
The English literature on this entity consists of only a few publications [16]
(For an extensive list
of previously published cases see References 6 and 8). Patients are generally elderly, presenting with
urinary obstruction, TURP being the most common tissue source of diagnosis. The youngest reported case
was 28 years old [1]. The outcome for patients diagnosed with basal cell carcinoma of the prostate is
uncertain, since most cases have been reported with a short follow-up. Overall, basal cell carcinoma of
the prostate is viewed as a low grade carcinoma [6].
A recent paper by Iczkowski et al [7] described the
clinico-pathological features in 19 cases and, based on their experience, they concluded that basal cell
carcinoma of the prostate (in their paper this tumor is referred to as adenoid cystic/basal cell
carcinoma) was a potentially aggressive neoplasm requiring ablative therapy. Such conclusion was based
on the fact that metastasis was documented in 21% of their cases, while two died of cancer and 3 were
alive with cancer.
Conclusions
- Prostatic basal cell proliferations range from ordinary
BCH to florid BCH and basal cell carcinoma.
- The separation between these three forms of BCH,
including the variant with prominent nucleoli, depends on morphological and immunohistochemical criteria.
- Immunohistochemistry is useful to identify the cell
composition of the basal cell proliferations, which includes the basal cell nature of the cells and
myo-epithelial differentiation.
Acknowledgements
This publication has been supported by grants from the Polytechnic University of the Marche Region (Ancona ) (MS) and the Italian Ministry of University and Scientific
Research (RM, 2003). The content of this paper is solely the responsibility of the authors and does not
necessarily represent the official views of the Polytechnic University of the Marche Region (Ancona ) ( Italy ).
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