Fine needle aspiration cytology of ductal breast carcinoma with neuroendocrine differentiation. Review of eight cases with histologic correlation

OBJECTIVE: To describe the fine needle aspiration cytology findings of ductal breast carcinoma with neuroendocrine differentiation and correlate them with the histologic appearance. STUDY DESIGN: We reviewed the cytologic features of eight cases of ductal carcinoma with neuroendocrine differentiation in the files of Pamela Youde Nethersole Eastern Hospital during the three-year period 1998-2000. Immunohistochemical study for neuroendocrine markers was performed, with ultrastructural correlation. RESULTS: All cases showed similar cytologic features. The smears were of moderate to high cellularity with predominantly dispersed or loosely cohesive tumor cells. The carcinoma cells were mostly of low cytologic grade. They possessed round and relatively uniform, eccentric nuclei; finely stippled chromatin; sometimes small, distinct nucleoli; and discrete cell borders. Abundant eosinophilic and focally granular cytoplasm was a common finding. In some of the cases there was accentuation of staining in the paranuclear region; it correlated with aggregates of dense core neurosecretory granules seen ultrastructurally. Mucoid substance was seen in the background in some of the aspirates. Histologic examination of the tumors showed invasive ductal carcinoma with an organoid growth pattern and sometimes mucinous component. The neuroendocrine differentiation was confirmed immunohistochemically. CONCLUSION: Although this subtype of ductal carcinoma probably carries no significant prognostic value per se, it has distinct cytologic features, rendering preoperative diagnosis possible. Recognition of this entity is important in order to avoid the misdiagnosis of neuroendocrine tumor metastatic to the breast.     

Stereotaxic fine needle aspiration cytology of clinically occult malignant and premalignant breast lesions

Stereotaxic fine needle aspiration (FNA) cytology was used to study clinically occult (nonpalpable) breast lesions in 114 consecutive patients with mammographically suspicious findings prior to excisional biopsy. The aspirate contained insufficient material for cytologic evaluation in 15 cases (13.2%), which were histologically diagnosed as benign (7 cases), atypical hyperplasia (7 cases) or carcinoma in situ (1 case). The cytologic findings indicated a benign lesion in 77 cases (67.5%), which were histologically diagnosed as benign (71 cases) or atypical ductal hyperplasia (6 cases). The cytologic sample showed atypia in eight cases (7.0%), which were histologically diagnosed as severe atypical ductal hyperplasia (three cases), carcinoma in situ (one case) or proliferative fibrocystic disease (four cases). In the eight cases (7.0%) cytologically interpreted as probably malignant, histology confirmed six invasive carcinomas, one carcinoma in situ and one fibrocystic disease. Of six cases (4.4%) cytologically reported as malignant, five were histologically diagnosed as invasive carcinoma and one as carcinoma in situ. Overall, stereotaxic FNA cytology reported as malignant or probably malignant 14 of the 15 cases with a histologic confirmation of malignancy, for a sensitivity of 93.3%. Cytology correctly identified 78 of the 83 histologically negative cases, for a specificity of 94.0%. The 16 cases histologically diagnosed as ductal hyperplasia, which carries a high risk for subsequent malignancy, were studied in detail in an effort to define histologic and cytologic criteria for this entity. Using selected histologic criteria, 11 of these cases were graded as showing mild-to-moderate atypical hyperplasia and 5 as showing severe atypical hyperplasia. Three of the latter cases were similarly identified by an analogous cytologic grading; the other two cases had insufficient cytologic samples. The total results in this series of 114 cases support the use of stereotaxic FNA cytology in the diagnosis of these nonpalpable breast lesions, examples of which are illustrated. In particular, it may help to raise the low specificity yielded by mammography alone, which would represent a significant advance for the patient in terms of the accuracy, expediency and reduced cost of diagnosing these lesions.     

Low-grade cribriform ductal carcinoma in situ of the breast. Fine needle aspiration cytology in three cases.

This paper presents the cytologic features of fine needle aspiration biopsy specimens from three cases of ductal carcinoma in situ characterized by small and uniform tumor cells growing in a predominantly cribriform pattern without comedo necrosis (low-grade cribriform ductal carcinoma in situ). On cytology, most of the tumor cells were clustered in three-dimensional ductal structures. Occasionally in the clusters the tumor cells were seen bordering central lumina, quite similar to the architecture in histology. A few single tumor cells and no myoepithelium were seen. The background was clear or slightly hemorrhagic, without necrosis. The tumor cells were uniform and had a cylindroid shape, with round or oval nuclei. Morphometrically the mean largest nuclear diameter was 1.5-1.6 times that of a red blood cell. The chromatin was finely granular, with a minute nucleolus and slight condensation along the nuclear membrane. In cut sections all three tumors showed strong immunoreactivity for neuron-specific enolase. Unless the cribriform growth pattern is recognized in the smear, the cytologic diagnosis of this entity is difficult.     

Fine needle aspiration cytology of epithelial-myoepithelial carcinoma of salivary glands. A report of three cases.

BACKGROUND: Epithelial-myoepithelial carcinoma is a rare, low grade malignant tumor of the salivary glands. Histologically, it has a biphasic cellular composition and exhibits a high degree of differentiation. The fine needle aspiration cytology of this rare tumor is rarely described in the literature. CASES: We report the fine needle aspiration cytology of three epithelial-myoepithelial carcinomas, arising in the right parotid, left parotid and minor salivary gland of the hard palate. Cytology showed a biphasic population consisting of cells of ductal epithelial and myoepithelial origin arranged in small clusters and sheets. The myoepithelial cells had small, uniform nuclei; ample, clear cytoplasm and distinct cell borders, while the ductal epithelial cells had larger, mildly pleomorphic nuclei and scanty cytoplasm. These ductal cells tended to form tubules among background sheets of clear myoepithelial cells. This feature, if present, was an important diagnostic clue. Hyaline material surrounding cell clusters and focal adenoid cystic carcinoma-like areas with orangeophilic globules were also not uncommon. CONCLUSION: While the cytologic appearance of epithelial-myoepithelial carcinoma may closely mimic that of other salivary gland tumors, such as adenoid cystic carcinoma, pleomorphic adenoma and basal cell adenoma, certain peculiar cytologic features may allow a distinction to be made on fine needle aspiration biopsy.     

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast. A case report

BACKGROUND: Invasive micropapillary carcinoma of the breast is uncommon and was characterized only recently. Awareness of this entity and its cytologic appearance is important to allow early diagnosis by fine needle aspiration cytology (FNAC). To our knowledge, only two cases of FNAC of this lesion have been reported in the English-language literature. CASE: An 80-year-old female presented with a firm, nontender mass in the upper outer quadrant of the left breast. FNAC showed ductal carcinoma, and mastectomy showed invasive micropapillary carcinoma. The patient had axillary metastases and received tamoxifen. CONCLUSION: The cytologic features of invasive micropapillary carcinoma are distinctive, with clusters of cells showing hyperchromatic, irregular and crowded nuclei and peripherally located cytoplasm with a rare central lumen. Fibrovascular cores are absent. Although FNAC experience with this lesion is limited, the characteristic cytologic features, including "inside-out" cell clusters, should raise the suspicion of this variant of ductal carcinoma. Differentiation from other papillary lesions and malignancies may be possible, but more experience is needed as the number of reported cases remains limited.     

Apoptosis in breast cancer

OBJECTIVE: To evaluate apoptotic rates on fine needle aspiration (FNA) samples of infiltrating duct carcinoma of the breast and to determine whether cytologic grading improved with consideration of the apoptotic rate in comparison with histologic grading. STUDY DESIGN: We studied 35 women who underwent mastectomy following an FNA diagnosis of infiltrating ductal carcinoma. Concordance between cytologic and histologic grades was calculated. Next, cytologic grades were considered with the apoptotic rates and compared with the histologic grades. RESULTS: An overall concordance of 82.9% was noted between the cytologic and histologic grading systems, with maximum concordance in grade 1 and minimum in grade 3 breast cancers. A highly significant difference in the apoptotic rates, as calculated on cytology, existed between the three histologic grades, indicating a significant increase in apoptosis with rising histologic grade. Applying multiple regression analysis, a significant improvement of cytologic grade with consideration of the apoptotic rate was observed. CONCLUSION: Employing histologic grade as the yardstick, cytology was less sensitive for the purpose of grading breast ductal carcinoma. However, by considering the apoptotic rates, the sensitivity of cytologic grading significantly rose in relation to histologic grade. Larger studies are required to determine whether apoptosis can be incorporated into the existing cytologic grading systems to increase their sensitivity.     

Pleomorphic lobular carcinoma of the breast. A case report

BACKGROUND: Pleomorphic lobular carcinoma of the breast is associated with aggressive behavior. CASE: Fine needle aspiration cytology was performed on a breast lump in a 55-year-old woman. The aspirates showed highly pleomorphic, large cells in a dyscohesive pattern, with a tendency of few cells to aggregate in small groups. A diagnosis of ductal carcinoma was made on cytology. On histology, the paraffin sections showed features of pleomorphic lobular carcinoma of the breast. CONCLUSION: The cytologic features of pleomorphic lobular carcinoma overlap with those of infiltrating ductal carcinoma. It is very difficult to make a diagnosis of pleomorphic lobular carcinoma prospectively on cytology. However, if Indian file arrangement and cytoplasmic vacuolation are present, pleomorphic lobular carcinoma must at least be suggested for the differential diagnosis as it has different clinical implications.     

Robinson cytologic grading of invasive ductal breast carcinoma: correlation with histologic grading and regional lymph node metastasis

OBJECTIVE: To evaluate the importance of cytologic grading of breast carcinoma and its association with histologic grading and the existence of axillary lymph node metastasis. STUDY DESIGN: Aspirates and surgical samples from 100 patients with invasive ductal breast carcinoma not otherwise specified were studied. In 50 patients, > or = 1 metastatic nodes were identified. The cytologic grade was evaluated using the Robinson method and the histologic grade using the Elston modification of the Bloom-Richardson method. A study was undertaken to establish the association between histologic and cytologic grades and to compare the various parameters used to evaluate cytologic grade with the presence of axillary node metastasis. RESULTS: A statistically significant association was observed between cytologic and histologic grades (p < 0.0005) and between cytologic grade and presence of axillary metastasis (p < 0.0005). Similarly, cell dissociation (p < 0.0005), cell uniformity (p = 0.0010) and the appearance of nuclear margins (p < 0.0005) all displayed a positive correlation with regional metastasis. CONCLUSION: Cytologic grade may provide relevant information on the aggressiveness of invasive ductal breast carcinoma and could be a useful parameter to take into consideration when selecting neoadjuvant therapy.     

Cytologic findings of atypical adenosis of the breast. A case report

BACKGROUND: Atypical apocrine adenosis, a well-described histopathologic entity, can sometimes be misdiagnosed as carcinoma. Apocrine cells can also appear atypical in cytopathology and be mistaken for carcinoma. Occasional case reports describe false positive cases due to the presence of apocrine cells in a few cases of radial scars and atypical apocrine metaplasia and in a degenerated cyst. CASE: A 37-year-old female underwent ultrasound-guided fine needle aspiration of an ill-defined breast nodule. The aspirate showed clusters and single cells containing abundant granular to focally vacuolated cytoplasm; enlarged, pleomorphic nuclei with irregular nuclear membranes; granular chromatin; and prominent nucleoli. These cells were distinct from and larger than the surrounding ductal and myoepithelial cells. Excision showed a nodular area of atypical apocrine adenosis adjacent to previous biopsy changes, correlating with the cytologic findings. CONCLUSION: Atypical apocrine adenosis can mimic carcinoma in histopathology and cytopathology. One should be cautious when reviewing apocrine cells in cytology, given their atypical features, especially their single, dispersed nature. However, the presence of accompanying benign cellular elements supports a benign diagnosis. Surgical biopsy should be recommended based on the cytologic findings.     

Fine needle aspiration cytology of high grade mucoepidermoid carcinoma of the breast: a case report

BACKGROUND: Primary mucoepidermoid carcinoma of the breast is a very unusual tumor. It is often misdiagnosed, masquerading under different diagnoses. The cytologic assessment is especially difficult when the lesion is high grade. One reported case was initially diagnosed by fine needle aspiration cytology. CASE: A 69-year-old woman presented with a 6 x 4-cm tumor located in the upper outer quadrant of the right breast. The first cytologic diagnosis suggested ductal carcinoma with atypical squamous metaplasia; further review disclosed that the clusters of epithelial ductal cells displayed a mixed pattern of glandular, squamous and intermediate cells. There also was a scant intracellular and extracellular mucous substance, confirming the diagnosis of mucoepidermoid carcinoma. Histochemistry and immunohistochemistry, performed on the tumor and lymph node metastases, showed cellular staining for periodic acid-Schiff, and keratin, epithelial membrane antigen and carcinoembryonic antigen demonstrated the epithelial origin. The high expression of Ki-67, as well as the finding of 24 metastasized nodes in the axilla, demonstrated the tumor's aggressiveness. CONCLUSION: Fine needle aspiration cytology is a very reliable tool in achieving a fast and accurate diagnosis of primary mucoepidermoid carcinoma of the breast.     

Fine needle aspiration cytology of invasive cribriform carcinoma of the breast with osteoclastlike giant cells: a case report

BACKGROUND: Nonneoplastic osteoclastlike giant cells are occasionally associated with carcinoma of the breast, pancreatobiliary and gastrointestinal systems. In the breast, this uncommon stromal response is seen mainly in invasive carcinoma with low grade cytology, among which invasive cribriform carcinoma is the classic example. Details of the fine needle aspiration cytology of this phenomenon, especially in thin-layer preparations, have been described rarely. CASE: The fine needle aspiration cytology of an invasive cribriform carcinoma of the breast occurred in a 66-year-old woman. Cytology showed cohesive sheets and three-dimensional cribriform clusters of bland-looking and mitotically inactive ductal cells in a blood-stained background. Scattered multinucleated, osteoclastlike giant cells, some containing hemosiderin granules, were also seen. Myoepithelial cells and naked nuclei were not obvious. The cellular composition was more discernible in liquid-based cytologic preparations. Histologic examination of the excisional biopsy showed an invasive cribriform carcinoma associated with many osteoclastlike giant cells in a hypervascular stroma. CONCLUSION: In view of the extremely low grade cytology of the malignant ductal cells, invasive cribriform carcinoma may closely mimic benign proliferative breast diseases on fine needle aspiration biopsy. Recognition of this special relationship with osteoclastlike giant cells, which are rarely present in certain subtypes of breast cancer but not benign lesions, can help to arrive at a correct cytologic diagnosis.     

Recurrence following treatment of ductal carcinoma in situ with skin-sparing mastectomy and immediate breast reconstruction

Skin-sparing mastectomy with immediate breast reconstruction can provide an excellent cosmetic result. Despite its increasing popularity, few studies have assessed the risk of recurrence when the procedure is used for the treatment of ductal carcinoma in situ. To evaluate the oncologic safety of skin-sparing mastectomy used for the treatment of ductal carcinoma in situ, the recurrence rate was analyzed. Patients with ductal carcinoma in situ or invasive carcinoma or both who underwent skin-sparing mastectomy with immediate breast reconstruction between 1985 and 1994 and had a follow-up period of at least 6 years were included in this retrospective analysis. The recurrence rates were determined for invasive carcinoma (with or without foci of ductal carcinoma in situ) and ductal carcinoma in situ alone. A total of 221 patients were included, 177 patients with invasive carcinoma and 44 patients with ductal carcinoma in situ alone. The immediate breast reconstructions were performed with transverse rectus abdominis muscle (TRAM) flaps in 62 percent of patients, implants in 34 percent of patients, and latissimus dorsi myocutaneous flaps (with or without implants) in 4 percent of patients. The local recurrence rate was zero of 44 for patients with ductal carcinoma in situ and 5.6 percent (10 of 177) for patients with invasive carcinoma during a mean follow-up period of 9.8 years. There was a 6.8 percent (12 of 177) metastatic recurrence rate in the invasive carcinoma group. All recurrences were invasive ductal carcinoma. Of the patients with ductal carcinoma in situ alone, none developed metastatic disease. The combined metastatic and local recurrence rates for the invasive carcinoma group (n = 177) with each type of reconstruction were 13 percent (14 of 110), 12 percent (seven of 60), and 14 percent (one of seven) for TRAM flaps, implants, and latissimus dorsi flaps, respectively. The risk of recurrence following skin-sparing mastectomy and immediate breast reconstruction for ductal carcinoma in situ is low during this follow-up period. Therefore, skin-sparing mastectomy with immediate breast reconstruction seems to be a safe oncologic treatment option for ductal carcinoma in situ; however, a longer follow-up period is important to determine the long-term risk of recurrence.     

Cytologic diagnosis of male breast cancer with nipple discharge. A case report

The cytologic findings in a nipple discharge from a male patient with breast cancer are described. Malignant epithelial cells and cell clusters believed to be derived from ductal carcinoma were observed. The subsequent mastectomy specimen contained a ductal carcinoma with minute foci of stromal invasion.     

Robinson cytologic grading in invasive ductal carcinoma of the breast: correlation with E-cadherin and alpha-, beta- and gamma-catenin expression and regional lymph node metastasis

OBJECTIVE: To correlate the cytologic grade of breast carcinoma with the expression of E-cadherin/catenin system molecules and the presence of metastasis in regional lymph nodes. STUDY DESIGN: Aspirate smears were examined together with histologic sections from the corresponding neoplasms taken from 100 patients with invasive ductal carcinoma. In 50 cases, > or = 1 metastatic nodes were identified. Cytologic grading of the smears was performed using the Robinson method. Immunohistochemical expression of E-cadherin and of alpha-, beta- and gamma-catenin was studied. RESULTS: A statistically significant relationship was observed between E-cadherin/catenin expression and cytologic grade (p < 0.0005). This association was particularly relevant to the cell dissociation parameter (p < 0.0005). CONCLUSION: The cytological grade established in preoperative studies may provide relevant information on the aggressiveness of invasive ductal carcinoma and its tendency to produce regional metastasis. This finding could be particularly useful in cases of breast carcinoma in which neoadjuvant therapy is the method of choice.     

Stereologic estimates of volume-weighted mean nuclear volume in aspiration smears of ductal breast carcinoma. Correlation with cytologic grade, tumor size and lymph node status

OBJECTIVE: To estimate cytologic volume-weighted mean nuclear volume and correlate it with other prognostic factors, such as tumor diameter and cytologic grading in relation to nodal infiltration. STUDY DESIGN: The relationships between nodal status and nuclear VV, tumor diameter and cytologic grading, according to the modified Black nuclear grading system, were analyzed on fine needle aspirates of 49 cases of breast cancer by univariate and multivariate logistic regression. RESULTS: Volume-weighted mean nuclear volume (nuclear VV) estimated on fine needle aspiration smears showed a significant correlation with grade of tumor differentiation. CONCLUSION: Stereologic evaluation of nuclear size by nuclear VV is an objective method for the cytologic grading of ductal carcinoma of the breast and has independent prognostic value in relation to nodal status higher than those of tumor diameter and cytologic grade.     

Ductal adenocarcinoma of the prostate: current opinion and controversies

OBJECTIVE: To evaluate the morphologic spectrum and clinical significance of ductal adenocarcinoma of the prostate (DAP). STUDY DESIGN: We reviewed diagnostic criteria, including the value of immunohistochemistry, and outlined the prognostic implications of a diagnosis of DAP. RESULTS: DAP is composed of tall columnar cells displaying nuclear pseudostratification and several architectural patterns, including cribriform, papillary, solid and invasive glandular. Typically, there is marked cytologic atypia and a high mitotic count, although in some cases cytologic atypia can be minimal, causing diagnostic difficulties, particularly in needle biopsies. DAP is found in both the periurethral region and peripheral zone of the prostate and is considered high grade in the modified Gleason grading system. Immunostaining for prostatic-specific antigen and prostate-specific acid phosphatase is present in these tumors, a high percentage of which overexpress alpha-methylacyl-coenzyme A racemase. A basal cell layer can be seen in some of these tumors, which is probably due to tumor growth into preexisting ducts. This usually represents an advanced stage of tumor progression and is not a precursor of invasive carcinoma. CONCLUSION: DAP are neoplasms of prostatic origin, and the terms endometrioid or endometrial adenocarcinoma are best avoided. The term ductal carcinoma is also inappropriate because this includes some urothelial carcinomas of ductal origin. DAP are aggressive tumors with a shortened average time to progression compared with acinar adenocarcinoma.     

Epithelial-myoepithelial carcinoma of the parotid. A case of ductal-predominant presentation with cytologic, histologic and ultrastructural correlations

BACKGROUND: The cytologic features of the usual type of epithelial-myoepithelial carcinoma (EMC) of the parotid, with myoepithelial cell predominance, is well described in the cytology literature. In contrast, the cytologic features of ductal-predominant-type EMC has not yet been reported. CASE: An 82-year-old male presented with a 2.7-cm parotid mass of two years' duration. Fine needle aspiration smears stained with Diff-Quik showed cohesive tissue fragments outlined by metachromatic fibrils scattered in abundant, smooth, bluish background material. Ultrafast Papanicolaou stain revealed sharply outlined, large ductal cells with smooth, round to oval nuclei, prominent nucleoli and abundant vacuolated cytoplasm; the cells were arranged tridimensionally in occasional follicles that contained thick secretions. Neoplastic myoepithelial cells were occasionally seen at the periphery of tissue fragments, most commonly hidden underneath the neoplastic ductal epithelium at a slightly different focal plane; the cells had small, oval, dark nuclei and inconspicuous cell borders. The nuclear area and cell size of the neoplastic ductal cells was two and three times, respectively, that of neoplastic myoepithelial cells. CONCLUSION: EMC, depending on the ratio of ductal to myoepithelial cell components, has different cytologic presentations. This case illustrates the ductal-predominant presentation of EMC.     

Diagnosing invasive cystic hypersecretory duct carcinoma of the breast with fine needle aspiration cytology. A case report

BACKGROUND: Cystic hypersecretory duct carcinoma (CHC) of the breast, first described in 1984, is a rare variant of duct carcinoma. Histologically it is characterized by the formation of dilated ducts and cysts containing an eosinophilic secretory product resembling thyroid colloid. The lining epithelium of the cysts atypically proliferates to form intraductal carcinoma. Only four cases of invasive cystic hypersecretory carcinoma have been reported. CASE: We present a case of invasive CHC with tumor emboli in many lymphatic spaces and axillary nodal metastases. The lesion was also evaluated by fine needle aspiration. Direct smears with Papanicolaou stain were highly cellular and had abundant, intensely staining, orange-to-gray-green thyroid colloid-like material. Epithelial cells, showing a variety of cellular patterns, were indistinguishable from usual ductal carcinoma cells. These cytologic findings may be characteristic enough to suggest cystic hypersecretory carcinoma. CONCLUSION: The cytologic features of CHC are distinctive and correlate with histology. This was the first presentation of colloidlike secretory material in cytologic material with Papanicolaou stain in such a case. Invasive CHC tends to have aggressive behavior. Cystic hypersecretory hyperplasia coexisted in this case.     

The validation of cervical cytology. Sensitivity, specificity and predictive values

Statistics and methods for the validation of the results of cytologic screening for cervical cancer and its precursors were examined. Many of the methods commonly used, including the calculation of sensitivity and specificity on raw data, contain flaws that undermine their conclusions. Using a large computerized database of 748,871 cytologic screenings of 277,842 women over a ten-year period, the value of screening was examined. Only subsequent histologic examinations within one year were accepted to validate positive initial cytologic diagnoses; only two subsequent cytologic screenings within the next three years were accepted to validate negative initial cytologic diagnoses that had not been followed by a histologic examination. Cases not meeting these criteria were excluded from the initial analysis. From these data, the predictive value of a negative cytologic examination was determined to be 99.8%; the predictive value of a positive cytologic examination was 73.4% for an initial diagnosis of mild-to-moderate dysplasia, 90.6% for a diagnosis of severe dysplasia/carcinoma in situ, 94.5% for a diagnosis of carcinoma in situ or microinvasive carcinoma and 95.5% for an initial diagnosis of invasive carcinoma. Cases with an initial "questionable" cytologic diagnosis had a positive predictive value of only 64.0%. Extrapolation from the validated cases to the entire screened population showed an overall sensitivity of 80% and a specificity of 99.4% for cytologic screening for cervical cancer. The sensitivity was slightly lower for mild and moderate dysplasia (78.1%) and slightly higher for carcinoma in situ and severe dysplasia (81.4%) and invasive carcinoma (82.3%).     

Differentiation of tumours of ductal and lobular origin: I. Proteomics of invasive ductal and lobular breast carcinomas

The vast majority of invasive breast tumors are ductal and lobular breast carcinomas. Despite the many similarities, some clinical follow-up data and the patterns of metastases suggest that these histological subtypes of breast cancer are biologically distinct. Few papers, however, describe immunohistochemical markers useful for differentiation of these carcinomas. Many investigations suggest that E cadherin protein expression is lost in lobular but not in ductal carcinoma. The absence of E-CD, as a partial loss of epithelial differentiation, may account for the extended spread of lobular carcinoma in situ and the peculiar diffuse invasion mode of invasive lobular carcinoma. Some investigations report the significance of E-CD associated proteins alpha-, beta-, gamma-catenin expression, as well as the usefulness of cytokeratins 5, 6, 8, 7 and thrombospondin in differentiating histological types of breast invasive carcinomas. Several reports have suggested the possibility that invasive ductal and lobular cancers differ with respect to expression of antigens involved in proliferation and cell cycle regulation. It has been shown that vascular endothelial growth factor expression, also the expression of maspin, a tumour suppressor gene product, is higher in ductal, than in lobular carcinoma. Expression of NKX3.1, a member of the NK-class of homeodomain, is highly restricted and is found primarily in lobular carcinoma. Some histological and immunohistochemical characteristics of pleomorphic lobular carcinoma are also discussed.