Maspin expression in carcinoma ex pleomorphic adenoma

AIMS: To investigate the presence and distribution of the protein maspin in carcinoma ex pleomorphic adenoma (CXPA).METHODS: Maspin expression was studied by means of immunohistochemistry in 16 cases of CXPA, using the labelled polymer method.RESULTS: According to the extent of invasion, the tumours were subdivided into: intracapsular (five cases), minimally invasive (four cases), and invasive (seven cases). Twelve patients had carcinoma with only epithelial differentiation, whereas four had a malignant myoepithelial component. Non-luminal cells in the duct-like structures of the remnant pleomorphic adenoma were strongly positive for maspin, whereas only a few luminal cells were immunopositive. A few positive cells were seen in the frequent hypocellular and hyalinised areas. Maspin was abundantly expressed, mainly in non-luminal cells, in transitional areas of CXPA with only epithelial differentiation. In frankly carcinomatous areas there was a gradual decrease in maspin expression. Almost all cells were maspin positive in CXPA with a myoepithelial component. When present, luminal cells were in general negative for maspin.CONCLUSIONS: When only epithelial cells undergo malignant transformation, maspin expression is gradually lost. In cases with a myoepithelial component, maspin expression is high, and this might be related to the tumour suppressor activity attributed to this cell.     

Biomarker analysis in carcinoma ex pleomorphic adenoma at an early phase of carcinomatous transformation

Diagnostic criteria for intracapsular carcinoma ex pleomorphic adenoma (CXPA) are subjective and vary among authors. Biomarker analysis, which could provide more objective evaluation of these tumors, has rarely been studied in intracapsular CXPA. Immunohistochemical evaluation of c-erbB-2, p53 protein, bcl-2, and Ki-67 was performed in 8 cases of CXPA at an early phase of malignant transformation (4 intracapsular and 4 minimally invasive) and in 17 pleomorphic adenomas (PA). In all cases of CXPA, p53 and Ki-67 were demonstrated predominantly in luminal cells of benign and malignant areas, significantly more in the latter. Few benign myoepithelial cells were p53 positive. c-erbB-2 reactivity was strongly associated with atypical luminal cells. Bcl-2 expression was weak and focal in malignant areas from 2 cases. In conclusion, both p53 and c-erbB-2 proteins appear to be involved at an early stage of malignization of PA. In PA with atypical cells, evaluation of the expression of these 2 markers provides more objective criteria for the diagnosis of intracapsular CXPA.     

Carcinoma ex pleomorphic adenoma of the salivary glands: distinct clinicopathologic features and immunoprofiles between subgroups according to cellular differentiation

In carcinoma ex pleomorphic adenoma (CXPA), pleomorphic adenoma (PA) and diverse carcinoma components showing luminal (ductal) or non-luminal (myoepithelial) differentiation coexist. To elucidate the clinicopathological implications of cellular differentiation in CXPA and the potential role of p53, vascular endothelial growth factor (VEGF), c-erbB-2, c-kit, and glucose transporter 1 (Glut-1) in carcinogenesis, we analyzed 11 CXPAs with luminal differentiation (CXPAs-LD) and 6 CXPAs with non-luminal differentiation (CXPAs-NLD) and compared protein expressions in residual PAs and carcinomas by immunohistochemistry. Among the CXPAs-LD, 5 were invasive and 8 were histologically high-grade tumors. The 5-year survival rate was 72.7%. P53, c-erbB-2, VEGF, and Glut-1 were more immunoreactive in carcinoma components than in PAs (P = 0.008, 0.004, 0.002, and 0.024, respectively); c-erbB-2 overexpression was associated with high histological grade (P = 0.024). Carcinoma components frequently lacked c-kit expression (P = 0.009). CXPAs-NLD were all low-grade and invasive with a larger mean tumor size (5.2 cm) than CXPAs-LD (3.3 cm) (P = 0.040). The patients remained disease-free without significant immunohistochemical expression. The immunoprofiles and clinical course of CXPA differed according to cellular differentiation. Therefore, it is important to report the histological subtype and to assess potential biomarkers in diagnostic and therapeutic trials.     

Tenascin and fibronectin expression in carcinoma ex pleomorphic adenoma.

This study was conducted to analyze the participation of tenascin and fibronectin, components of the extracellular matrix, in different types of carcinoma ex pleomorphic adenoma (CXPA). Seventeen cases of CXPA, classified according to the presence of epithelial and myoepithelial cells and the degree of invasion-intracapsular, minimally, and frankly invasive carcinoma-were immunohistochemically labeled for tenascin and fibronectin. Normal salivary gland included in the specimens showed tenascin only around the excretory duct, and fibronectin slightly expressed all over the stroma of the gland. In reminiscent pleomorphic adenoma, tenascin and fibronectin were observed around tubular structures and in the stroma. Both tenascin and fibronectin were expressed in all the CXPA studied. In areas of in situ carcinoma of the intracapsular type, the expression of these extracellular matrix proteins was enhanced compared with areas of residual pleomorphic adenoma. In intracapsular and minimally invasive types of CXPA, some areas of the tumor border presented tenascin and no fibronectin, pattern that may represent the real invasive front. In frankly invasive CXPA type with only epithelial component, fibronectin was strongly observed in a fibrillar network pattern, and tenascin was only focal. In frankly invasive type with myoepithelial component, tenascin staining was very strong and diffuse. This study showed different patterns of expression of tenascin and fibronectin along the process of tumorigenesis and tumor progression in CXPA, a fact that might play a role in invasion properties of these tumors.     

Lymphatic vascular density and lymphangiogenesis during tumour progression of carcinoma ex pleomorphic adenoma

AIMS: To assess lymphatic vascular density (LVD) and lymph vessel endothelial proliferation in a series of carcinoma ex pleomorphic adenoma (CXPA) that represents the tumour in the different carcinogenesis phases and tumour progression. METHODS: In 8 cases of early CXPA (intracapsular and minimally invasive tumours), 8 of advanced CXPA (widely invasive tumours) and 10 of pleomorphic adenoma (PA) without malignant transformation, lymphatic vessels and proliferating cells were detected using the antibodies D2-40 and Ki-67 respectively. RESULTS: Comparing early tumours with advanced ones, LVD was not significantly different at the tumour margin. In contrast, regarding intratumoural lymphatics, PA without malignant transformation and early CXPA contained rare, if any, lymph vessels, whereas in widely invasive carcinomas they were more numerous. However, neither intratumoural nor peritumoural LVD were increased in comparison to adjacent normal salivary gland tissue. In no case did dual immunohistochemistry using D2-40 and the cell proliferation marker Ki-67 reveal the existence of proliferating lymphatics. Carcinomatous emboli were found in peritumoural as well as in intratumoural lymphatics only in advanced CXPA without myoepithelial differentiation. CONCLUSION: In CXPA, the lymphatic network is mainly composed of pre-existing lymphatics which are rare in tumours that have not infiltrated outside the confines of the original PA. In the widely invasive CXPA, intratumoural as well as peritumoural lymphatics are a conduit for carcinoma cells, but in carcinomas with myoepithelial differentiation, the neoplastic cells seem to have a lower invasion capacity.     

Angiogenic switch during tumor progression of carcinoma ex-pleomorphic adenoma

We analyzed the tumor vascularization in carcinomas ex-pleomorphic adenoma (CXPA) to investigate the angiogenic switch during the malignant transformation of pleomorphic adenoma (PA) to carcinoma and during tumor progression. In eight cases of early CXPA (intracapsular and minimally invasive tumors), eight of advanced CXPA (widely invasive tumors), and ten of PA without malignant transformation, tumor vascularization was assessed in histological samples by measuring total microvascular area (TVA) and microvessel density (MVD) using CD34 and CD105 antibodies. MVD for CD105 increased significantly during tumor progression, whereas this was not the case for CD34 MVD. Comparing widely invasive CXPA with and without myoepithelial differentiation, CXPA with myoepithelial differentiation showed a significantly lower number of CD105 positive vessels but revealed higher TVA values. In these tumors, the neoplastic cells usually formed larger hypovascularized aggregates that were often surrounded by large-sized vessels. In conclusion, the antibody CD105 reveals an angiogenic switch during the progression from adenoma to carcinoma in salivary glands. The degree of angiogenesis and the total vascular area have distinctive patterns in CXPA with and without myoepithelial differentiation. Low angiogenesis associated with high TVA value is more characteristic of CXPA with myoepithelial differentiation.     

Cyclin D1 and p16 expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid gland

AIMS: To compare cyclin D1 and p16(ink4) (p16) expression in normal tissue, pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland. METHODS AND RESULTS: Immunohistochemistry was used to examine cyclin D1 and p16 expression in 43 parotid tumours (29 PAs and 14 CXPAs). Cyclin D1 and p16 were both significantly more likely to be expressed in the neoplastic than in the normal epithelial and stromal components of PA and CXPA (P < 0.001 and P < 0.005, respectively). Cyclin D1 was more likely to be expressed in the malignant components of CXPA than in the benign components of PA (50% versus 31% and 31%, respectively), but the trend was not statistically significant. There was no evidence of this association for p16 (corresponding positivity rates 69% versus 81% and 52%). CONCLUSIONS: Our findings provide preliminary evidence of roles for cyclin D1 and p16 in the development of PA and for cyclin D1 in the progression of PA to CXPA.     

Carcinoma ex pleomorphic adenoma: A diagnostic challenge on cytology

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a malignant neoplasm arising from primary or recurrent benign pleomorphic adenoma. It is rare with an annual incidence rate of 0.17 tumors per million. Histopathology remains the gold standard for the diagnosis of Ca ex PA, with only a handful of cases reported on cytology. In our case a 66‐year‐old male presented with the right parotid mass for 5 years rapidly increasing for the last 3 months. Fine needle aspiration cytology (FNAC) smears showed malignant tumor cells in clusters along with benign myoepithelial cells in chondromyxoid background. Histopathologically, highly pleomorphic malignant epithelial cells in sheets along with foci of comedonecrosis and areas corresponding to benign pleomorphic adenoma were observed on careful scrutiny. Immunohistochemistry revealed positivity for cytokeratin (CK 7) and gross cystic disease fluid protein 15 (GCDFP‐15) while CK5/6 and high molecular weight CK (34 βE12) were negative in the malignant tumor cells. So, the final impression was Ca ex PA with salivary duct carcinoma as malignant component. We hereby report this case to highlight the significance of FNAC in the diagnosis of Ca ex PA which can be easily missed on cytopathology. However, it is important to corroborate the cytological findings with clinical suspicion of malignancy as well as radiology. Diagn. Cytopathol. 2017;45:651–654. © 2017 Wiley Periodicals, Inc.     

Neural EGFL like 2 expressed in myoepithelial cells and suppressed breast cancer cell migration

Breast tissue has a branching structure that contains double-layered cells, consisting primarily of luminal epithelial cells inside and myoepithelial cells outside. Ductal carcinoma in situ (DCIS) still has myoepithelial cells surrounding the cancer cells. However, myoepithelial cells disappear in invasive ductal carcinoma. In this study, we detected expression of neural EGFL like (NELL) 2 and one of its receptors, roundabout guidance receptor (ROBO) 3, in myoepithelial and luminal epithelial cells (respectively) in normal breast tissue. NELL2 also was expressed in myoepithelial cells surrounding the non-cancerous intraductal proliferative lesions and DCIS. However, the expression level and proportion of NELL2-positive cells in DCIS were lower than those in normal and non-cancerous intraductal proliferative lesions. ROBO3 expression was decreased in invasive ductal carcinoma compared to that in normal and non-cancerous intraductal proliferative lesions. An evaluation of NELL2's function in breast cancer cell lines demonstrated that full-length NELL2 suppressed cell adhesion and migration in vitro. In contrast, the N-terminal domain of NELL2 increased cell adhesion in the early phase and migration in vitro in some breast cancer cells. These results suggested that full-length NELL2 protein, when expressed in myoepithelial cells, might serve as an inhibitor of breast cancer cell migration.     

Carcinoma ex pleomorphic adenoma

Carcinoma ex pleomorphic adenoma is an epithelial malignant neoplasm arising from a primary or recurrent pleomorphic adenoma and is a diagnostic challenge for cytopathologists. Diagnosis requires that elements from the benign pleomorphic adenoma and the malignant component need to be seen. We report a case of carcinoma ex pleomorphic adenoma in a patient presenting with left facial nerve palsy and a painless left parotid lump. Ultrasound imaging revealed a suspicious parotid mass and FNA cytology showed background benign myoepithelial and ductal cells, chondro-myxoid stroma, and overtly malignant epithelial and myoepithelial cells; features consistent with carcinoma ex pleomorphic adenoma. A radical parotidectomy was performed and histology confirmed the diagnosis of invasive salivary duct carcinoma ex pleomorphic adenoma. Early diagnosis of carcinoma ex pleomorphic adenoma is important and cytology plays a key role; however, findings should be correlated with radiology and clinical history and the potential limitations of cytology should be appreciated.     

Cytological features of carcinoma ex pleomorphic adenoma of the salivary glands: A diagnostic challenge

Carcinoma ex pleomorphic adenoma (CXPA) of the salivary glands is a relatively rare carcinoma. The detection rate of the carcinoma component in the cytological specimens is not high and may be challenging in cytological examination. The purpose of the present study was to analyze the cytological specimens of CXPA with emphasis on the detection of the carcinoma component. We reviewed the cytological characteristics of patients histopathologically diagnosed with CXPA who underwent preoperative cytological examination. Of the 10 patients enrolled in the study, 8 had tumors located in the parotid gland, and 2 in the submandibular gland. A review of the cytological specimens revealed the presence of the carcinoma component in all 10 cases and the pleomorphic adenoma (PA) component in 6 cases, although initial cytodiagnosis detected the carcinoma component in 8 cases. The cytological feature of this component was the presence of variable‐sized clusters of polygonal cells with relatively rich cytoplasm and large round to oval nuclei in a necrotic background. Interestingly, carcinoma cells mixed with the PA component were also present. On histopathological analysis, 7 cases were intracapsular, and the remaining 3 cases were widely invasive CXPA. Further, 9 cases had salivary duct carcinoma as carcinoma component. In conclusion, these findings show that careful detection of the carcinoma cells, particularly within the PA component, is crucial for early detection of CXPA, and the presence of necrosis might help with the detection of the carcinoma component.     

Cyclin A expression and its diagnostic value in pleomorphic adenoma and carcinoma expleomorphic adenoma of the parotid gland

AIMS: To investigate cyclin A expression in pleomorphic adenoma (PA) and carcinoma expleomorphic adenoma (CXPA) of the parotid gland with a view to assessing its potential value as a diagnostic marker for CXPA. METHODS AND RESULTS: Cyclin A expression in PA and CXPA was studied using semiquantitative immunohistochemistry. The epithelial component of the tumours expressed cyclin A in a statistically significantly (P < 0.005) higher number of CXPA cases (86%) compared with the PA cases (39%). Cyclin A was not expressed in normal salivary tissues of PA and CXPA. CONCLUSIONS: High cyclin A expression is a useful marker for the pathological diagnosis of CXPA.     

The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast

BACKGROUND: Histological differentiation of mammary papillary lesions can be difficult. The evaluation of myoepithelial cells can be helpful, with benign papilloma showing a continuous myoepithelial cell layer, which becomes attenuated or absent in malignant papillary lesions. METHODS: A large series of 100 papillomas (28 papillomas with florid epithelial hyperplasia) and 68 papillary carcinomas (9 invasive, 44 in situ, and 15 ductal carcinomas in situ (DCIS) involving papillomas) of the breast were stained for myoepithelial cells by immunohistochemistry using antibodies to smooth-muscle actin (SMA), p63, CD10 and cytokeratin (CK) 14. RESULTS: In the papillomas, using these four antibodies, myoepithelial cells were positive in 88%, 99%, 91% and 95% of cases, respectively, with SMA showing marked stromal component cell staining and CD10 showing epithelial and stromal staining. CK14 also showed epithelial staining in 71% of papillomas and 96% of papillomas with florid epithelial hyperplasia. In the papillary carcinomas, 36 (53%) cases showed staining of myoepithelial cells that were scattered, discontinuous and diminished in number and the remaining 32 (47%) cases did not show myoepithelial cells. Invasive papillary carcinoma has the lowest proportion (33%) with myoepithelial cells, and DCIS involving papillomas had the highest proportion (87%). CONCLUSIONS: p63 had the highest sensitivity and did not cross-react with stromal cells and only rarely with epithelial cells. CK14 has the added ability to distinguish between florid epithelial hyperplasia involving papilloma and DCIS involving papillomas. CK14 and p63 may be used as an adjunct in assessing difficult papillary lesions of the breast.     

乳腺良恶性病变中CD10表达及意义

目的 探讨CD10免疫标记乳腺肌上皮细胞的可行性。方法 收集50例乳腺良恶性病变的石蜡包埋标本(腺瘤、纤维腺瘤、叶状肿瘤、纤维囊性病、导管内乳头状瘤、乳头腺瘤、导管内癌、小叶内癌、浸润性导管癌、浸润性小叶癌)，采用免疫组化(S-P法)检测CD10在上述病变中的表达。结果 在乳腺良性病变中，CD10阳性的肌上皮细胞连续地环绕在普通型增生的小导管的周围。但在囊性扩张或不典型上皮增生的导管周围，CD10阳性细胞不连续，甚至不见阳性细胞。导管原位癌的癌细胞巢外周的阳性细胞由完整到不完整，甚至完全缺失。在浸润性癌中癌巢周围不见阳性细胞，在早期浸润性癌中可见残存的阳性细胞。除少许癌细胞和肌纤维母细胞表达CD10外，其余癌细胞、肌纤维母细胞、血管平滑肌细胞和上皮细胞均不表达CD10。结论 CD10标记肌上皮细胞具有较高的敏感性和特异性，可以作为肌上皮细胞的有效标记物。     

Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast

AIMS: This study was performed to determine the diagnostic value of keratin 5/6 (CK 5/6) immunophenotyping on routinely processed breast tissues. METHODS AND RESULTS: Six hundred and ninety-nine breast lesions, including normal tissues as well as benign and malignant lesions in 321 formalin-fixed, paraffin-embedded samples from 158 different patients were investigated immunohistochemically, following wet autoclave pre-treatment for antigen retrieval. In normal breast tissues, both myoepithelial and luminal epithelial cells expressed CK 5/6 in varying amounts. While myoepithelial immunoreactivity was most pronounced in the duct system, luminal epithelial immunoreactivity was strongest in the terminal duct lobular units. In ductal hyperplasias (DH), luminal epithelial cells predominantly revealed CK 5/6 immunoreaction. In contrast, neoplastic epithelial cells in atypical ductal and lobular hyperplasias (ADH and ALH) lacked such an expression, whereas in ductal in-situ carcinomas (DCIS) and in infiltrating ductal carcinomas 3.7% and 7.7%, of the cases respectively, showed positive immunostaining for CK 5/6. CONCLUSIONS: Immunophenotyping of keratin 5/6 expression can be helpful in the diagnosis of atypical hyperplasias and in-situ carcinomas of the breast. It is particularly valuable in the differential diagnosis between benign and atypical proliferative lesions.     

Diagnostic utility of p75 neurotrophin receptor (p75NTR) as a marker of breast myoepithelial cells.

We evaluated the low affinity neurotrophin receptor (p75NTR) as a marker of breast myoepithelial cells. Immunohistochemical staining for p75NTR was performed on paraffin sections of 122 malignant breast lesions, 28 benign lesions and the adjacent normal breast tissue. The staining pattern was compared to those of myosin heavy chain and p63. p75NTR immunostain was consistently positive and compatible with p63 and myosin immunoreactivity in the myoepithelial cells of the normal mammary gland, benign breast lesions (six usual ductal hyperplasias, six specimens with sclerosing adenosis, eight intraductal papillomas, six fibroadenomas), and carcinoma in situ (18 ductal carcinomas in situ, two noninvasive papillary carcinomas, two lobular carcinomas in situ). The luminal cells were negative for p75NTR, but rare positive cells were noticed in the solid areas of some of the usual ductal hyperplasias. Four of 64 invasive ductal carcinomas (6%) and all metaplastic carcinomas (n = 3, 100%) showed a variable degree of p75(NTR) positivity. No p75NTR expression was found in the malignant cells in all in situ carcinomas, invasive lobular carcinomas (n = 11), tubular carcinomas (n = 10), invasive papillary carcinomas (n = 6), mucinous carcinomas (n = 4), and medullary carcinomas (n = 2). No myosin immunoreactivity was seen in the luminal/tumor cells, but p63 pattern of staining in the luminal/tumor cells was quite similar to that of p75NTR. Although significant p75NTR immunoreactivity was noticed in the vessels, nerves, and stromal component of fibroadenomas, no difficulties in the evaluation of the immunostain of myoepithelial cells were encountered. Our study shows that p75NTR is a useful marker for breast myoepithelial cells and can be used to rule out invasive disease as well as to evaluate difficult for diagnosis sclerosing lesions. Our data suggest a role of neurotrophins in the development of fibroepithelial breast tumors and some of the breast carcinomas.     

The clinical use of a P63/cytokeratin7/18/cytokeratin5/14 antibody cocktail in diagnostic breast pathology

An antibody cocktail directed against p63, cytokeratin (CK)5/14, and CK7/18 is reported to be useful in distinguishing noninvasive from invasive breast lesions and for the characterization of intraductal epithelial proliferations. However, limited studies evaluate its use in clinical practice. A retrospective review of breast material at a university medical center identified cases that were immunostained with the above antibody cocktail. Additional p63 immunostaining alone was performed to further determine the utility of the antibody cocktail in the evaluation of invasion. Of 50 breast cases identified, the antibody cocktail was used to confirm or exclude invasion in 44 (88%). Twenty-two (50%) of these had easily identifiable p63/CK5/14-positive myoepithelial cells, whereas the remainder lacked such staining, confirming the diagnosis of invasive carcinoma. In 27 cases with available diagnostic material for additional p63 immunostaining, the cocktail better highlighted myoepithelial cells by staining nuclei and cytoplasm. Easier identification of invasion was also facilitated by CK7/18 expression in invasive foci, especially those composed of single cells. Ten cases were immunostained to help determine the nature of an intraductal proliferation. The cocktail demonstrated a mosaic staining pattern of both CK7/18- and CK5/14-positive epithelial cells in 3 (30%) cases consistent with usual hyperplasia; homogenous CK7/18 expression in the remaining cases supported the diagnosis of atypical ductal hyperplasia or carcinoma in situ. In summary, the p63/CK7/18/CK5/14 cocktail stain appears to be a useful tool in diagnostic breast pathology, in the evaluation of possible invasion, particularly in the setting of minute foci of invasion as well as in epithelial proliferations.     

Expression of maspin is up-regulated during the progression of mammary ductal carcinoma

AIMS: The tumour suppressor gene maspin is reported to inhibit the motility, invasiveness and metastasis of breast cancer cells. Maspin is expressed in normal mammary myoepithelial cells but is down-regulated during the progression of ductal carcinoma. However, we recently reported that maspin expression was frequently observed in invasive ductal carcinoma (IDC) with an aggressive phenotype, and it was a strong indicator of a poor prognosis. To our knowledge, to date, there has been no report investigating maspin expression in a large series of ductal carcinoma in situ (DCIS). METHODS AND RESULTS: To clarify whether there is down-regulation during the progression of ductal carcinoma, we immunohistochemically investigated the expression of maspin in 145 DCIS, 92 invasive ductal carcinomas with a predominant intraductal component as well as 94 usual ductal hyperplasias and 27 atypical ductal hyperplasias. The expression of maspin in carcinoma cells was observed in 9.6% (14 of 145) of DCIS and 18.5% (17 of 92) of IDC with a predominant intraductal components. It significantly correlated with larger tumour size (P = 0.013; P = 0.042), higher histological grade (P = 0.015; P = 0.0003) and the presence of comedo-necrosis (P = 0.000005; P = 0.0074) in DCIS and IDC with a predominant intraductal components, respectively. In epithelial cells, the expression of maspin was observed in only one case of usual ductal hyperplasia, and all cases of atypical ductal hyperplasia were negative. CONCLUSIONS: These results and our previous investigation in which 27.4% of IDC were positive for maspin suggest that the expression of maspin in epithelial cells could be up-regulated during the progression of ductal carcinoma, and that it could be correlated with the acquisition of an aggressive phenotype.     

Assessment of invasion in breast lesions using antibodies to basement membrane components and myoepithelial cells.

This paper describes immunostaining of consecutive sections from 15 cases of fibrocystic change of the breast (including 2 examples of intraductal papilloma), 4 ductal carcinomas-in-situ and 17 invasive carcinomas (4 tubular, 1 papillary, 2 lobular and 10 infiltrating ductal, NOS) with antisera to components of the basement membrane (BM), type IV collagen and laminin, and with the muscle antibodies actin and muscle-specific actin. A simple digestion technique was developed to improve the clarity of BM staining with these antibodies. The BM stains facilitated identification of small invasive foci through breaks in the BM in 2 of the cases which had been reported as pure intraductal carcinoma. Tubular carcinomas were surrounded by abnormal, fragmented, and focally discontinuous BM, a feature which could be used to distinguish this well-differentiated breast carcinoma sub-type from sclerosing adenosis, in which individual acini were invariably surrounded by a continuous BM. BM staining emphasized the fibrovascular core of intraductal papillomas, whereas the BM layer was absent in intraductal, cytologically malignant, papillary projections. Similarly, myoepithelial cells, stained with antisera to muscle actins, were identified in a continuous layer surrounding benign epithelial proliferations. These immunohistochemical staining techniques may thus assist the diagnostic histopathologist in differentiating between benign epithelial proliferations of the breast and well-differentiated invasive breast carcinoma, and in identifying foci of microinvasive carcinoma.     

Das pleomorphe Adenom

In the majority of cases the diagnosis of pleomorphic adenoma (PA) is straightforward. In “monomorphic” types of PA problems may result: Epithelial-rich PA need to be distinguished from basal cell adenoma or canalicular adenoma. PA dominated by mesenchymal, spindle-shaped differentiation need to be distinguished from myoepithelioma or soft tissue tumours like schwannoma. Focal biphasic-tubular differentiation with CK7/18-positive ductal cells is good evidence for a tumour within the wide spectrum of PA. Focal peripheral pseudoinfiltration can represent physiological growth pattern of PA; this may render a difficult distinction from low-malignant carcinomas like adenoid-cystic or epithelial-myoepithelial carcinoma, harbouring also tubular structures. The different progression steps of carcinoma ex pleomorphic adenoma (CEPA), starting with intraductal carcinoma, are highly relevant with respect to prognosis and therapy. Early stages including CEPA with minor extracapsular invasion show favourable prognosis, while cases with extensive extracapsular invasion carry a dismal prognosis.