Morphology Changes And Pathological Significance Of Basal Cells In Benign And Malignant Prostate Epitheliopathy

Purpose To investigate the clinico-pathological features of basal cells in prostate epitheliopathy which can help pathological diagonosis of prostate lesions and their differential diagnosis.Methods One hundred and eighty five cases of prostate carcinoma and three hundred and eighty five benign prostate hyplasia have been examined by hematoxylin-eosin stain,and 136 cases which were easily misdiagnosed between benign and malignant lesions were chosen in this research. Among these cases,twenty cases of benign lesion include nine cases of Basal cell hyperplasia(BCH) and eleven cases of Postatrophic hyperplasia(PAH); forty eight cases of boundary lesion include eight cases of atypical basal cell hyperplasia (ABCH), twelve cases of atypical adenomatous hyperplasia (AAH) and tweny eight Prostatic intraepithelial(PIN); Sixty eight cases of malignant lesion include thirty five cases of Prostatic duct adenocarcinoma (PDA) and thirty three Prostatic adenocarcinoma (PaC). And twenty cases of Normal prostate (NP) and twenty cases of Benign prostate hyplasia (BPH) were chosen as control cases. All cases were studied by hematoxylin and eosin stain and immunohistochemical stain of two-step Elivision? Plus method to detect the expression of cytokeratin of high molecular weight (34βE12), P63,α-methylacyl CoA racemase AMAC(P504S), Prostate specific antigen (PSA )and Prosate acid phosphatase(PSAP).And four cases of NP, four cases of BPH, two cases of PIN and three cases of PaC were observed by transmission electron microscope (TEM).Results(1) Pathological features of benign prostate:In twenty cases of NP, basal cells were arranged in monolayer and 34βE12 or p63 stainned as circular thin lines. In twenty cases of BPH,basal cells were arranged in double-deck or multilayer and 34βE12 or p63 stained as circular bold lines.In nine cases of BCH the basal cells were multi-layered and arranged around the prostate glands like annulation, off-center flower bud, foramen, sacculiform, lamellar, irregularity nest and so on. 34βE12 or p63 staining were in accordance with the feature of the basal cell proliferation and arrangement in these cases. PSA and PSAP staining in basal cells were negative or weaker than that in epithelial cells and in some region PSA and PSAP staining of epithelial cells were weaker than that in NP cases. P504S staining was negtive in all nine cases of BCH.In eleven cases of PAH,increased unequal gland alveolus with big dilated and small acini packed closely were observed.Positive staining of 34βE12 or p63 around the glands with negtive P504S staining of the glands were observed. In 3 cases PSA and PSAP staining of small acini were weaker than that of dilated acini. Combining with the morphology feature,basial cell marker(34βE12 and P63)and epithelial cell marker(P504S), it is easily to make definite diagnoses of PAH.2 Pathological features of prostate boundary lesionIn all the forty eight cases,there were eight cases of ABCH basically constituted by small acinis which were hyperplased nodularly. Basal cells were multi-layered and arranged around the glands like annulation or focally packed together. Antibody labeling of 34βE12 or p63 identified basal cells with positive or prominent staining, but staining of PSA and PSAP for the secretory epithelium cells were weaker than that in NP. And P504S staining was negtive in all eight cases of ABCH.AAH is a kind of of well-demarcated adenomatoid hyperplasia nodular lesion with clusters of acinis in prostate. The hyperlastic acinis are often variant in size and shape, with little stromal tissue. Clear cytoplasm and undistinguished nuclus were observed in cuboidal or columnar epithelial cells in the glands with discontinuous basal cells. The adenomatoid hyperplasia nodular lesion were usually originated from prostate duct and acinis. In this work, twelve cases of AAH acini were hyperplased nodularly in a disarranged pattern with intact structure and uncertain basal cells. Throgh immunohistochemical stain of 34βE12, P63 and P504S , almost intact basal cells were observed in five cases and partly intact basal cells in the other seven cases around all hyperplastic acini.Of the twenty cases of PIN,a total absense of basal cells in six cases with negative P504S staining; partly absense of basal cells in fourteen cases with weak or focal positive P504S staining but no obvious atypia tumor cells in four cases and intact basal cells in eight cases were observed by IHC which were uncertain in HE staining. 3 Pathological features of malignant epithelial prostate lesionThirty five cases of sixty eight cases were diagnosed as PDA. Nearly intact basal cells in thirteen cases; small amounts of incomplete basal cells in 3 cases;and totally absence of base cells in nineteen cases were observed by immunohistochemical staining which were were uncertain in HE staining. Twenty seven cases with P504S postive ,34βE12 negative and P63 negative staining in the edge of small invasive carcinoma and/or small acinous carcinoma around the prostatic duct adenocarcinoma were also observed.Thirty three cases of PaC cells were of clear,foamy cystoplasm, and basal cells were uncertain by light microscope.No intact basal cells were observed in malignant acini by IHC staining. In two cases few basal cells were observed around individual malignant acini. In twenty nine cases with positive P504S staining and five cases with negtive P504S staining while positive or prominent PSA and PSAP staining of in malignant acini of all thirty three cases were observed.4 Observation by electron microscopeThe ultramicrostructure of 12 cases of prostate lesions were studied.In three cases of NP, small basal cells arranged parallelly to basal lamina and secretory epithelium with desmosome and hemidesmosome, but few cell organs, and no myofilament were observed. In four cases of BPH, basal cell was similar to that in NP with complete basal lamina and increased cell layers distributed non-uniformly. Degenerative fibroblasts, fibrocytes, smooth muscle cells, collagen fiber and inflammatory cells were observed in interstitial tissue of BPH. In two cases of PIN intact or partly absent basal cells with multi-layer, and large nucleus or increased nucleoli, blurring of cell bounds were observed. In 3 cases of PaC which were poorly differentiated , the ultramicrostructure pattern of malignant cells were similar, and aboudant cytoplasm, secretory vacuole, pinosome, mitochondria , endoplasmic reticulum ,large and irregular nucleus and distinct nucleoli were observed .Conclusions1 Basal cells play an important role in differential diagnosis between benign and malignant prostate lesions.Light microscopy has its limitation in identifying basal cells accurately and may cause misdiagnosis.According to the this research, basal cells in eighty five percent cases need to be identified by ICH staining. For this reason, ICH staining of basal cells are very necessary in diagnosis of prostate lesions,such as carcinoma. 2 In benign prostatic proliferative lesions,basal cell layers are intact on the whole., although it is easily to make definite diagnoses of NP and BPH by light microscopy of hematoxylin-eosin staining, basal cell labelling technique is still of benefit to make correct diagnosis ot them . BC and PAH are rare benign proliferative lesion easily misdiognosed as adenocarcinoma by light microscopy of hematoxylin-eosin staining, hence basal cell marker of 34βE12 and p63 combining with malignant epithelial marker of P504S labelling are useful in diagnosis and differential diagnosis of these diseases .3 In prostate boundary lesions, basal cells arrangement are in different patterns such as intact, partly absent or discontinous cell layers, and the uncertainty make it difficult to make diagnosis and differential diagnosis between prostate boundary lesions. ABCH and AAH are rare prosate lesions with low morbidity and tend to be misdiagnosed as prostate carcinoma. The functionof 34βE12 and p63 staining in differential diagnosis between ABCH and AAH is yet uncertain. And the function of P504S staining in differential diagnosis between benign and malignant lesion is also in dispute. Our research demonstrate that basal cell marker(34βE12 and P63)combining with epithelial cell marker(P504S)as well as morphology observation are of great importance in differential diagnosis of prostate boundary lesion and other prosate tumor-like lesions such as ABCH and AAH. In addition, Although basal cells were intact in most PIN, there remained a high incidence of partly absense of basal cells in some cases ,which revealed that the intact of basal cells was not the most significant index on diagnosis of prostate intraepithelial neoplasia ,and too much relying on this index may lead to misdiagnosis and missed diagnosis.4 In malignant epithelial prostate lesion,it is generally accepted that basal cell are absent on the whole. In our study ,some special type of carcinoma, such as PDA, although obvious absence of basal cells was usually observed, basal cells still existed in the tumor tissues of some cases with a relative high rate. Basal cells exist mainly in PDA tumors around large or complete ducts of carcinoma nest which indicated that the absence of basal cells is not the most significant index to the pathological diagnosis of prostate duct adenocarcinoma, and doctors should not rely too much on the pattern of basal cells arrangement, histological structure, cell morphology and IHC staining should be taken into consideration in diagnosis of prostate duct adenocarcinoma lest misdiagnosis and missed Diagnosis happend. 5 The common ultramicrostructure of NP and BPH is that they all have complete basal lamina and regularly arranged, benign morphous and no myofilament basal cells. intact or partly absent basal cells with multi-layer and complete basal lamina are the mutual ultramicrostructure of prostate boundary lesions . Obviously allotype ,large and irregular nucleus and distinct nucleoli is the common ultramicrostructure of poorly differentiated PaC. Although ultramicrostructure is very useful in observe the basal cell, it is disadvantage for differential diagnosis of prostatosis in clinic pathological diagnosis because of selection cutting.