Paucity of fibronectin in invasive lobular carcinoma of breast

Fifty-four cases of invasive carcinoma of breast were immunostained for fibronectin and laminin. They included 36 cases of invasive ductal carcinoma and 18 cases of invasive lobular carcinoma. Although there was some heterogeneity within tumours, it was found that whilst the majority of ductal carcinomas (31/36) had abundant fibronectin at cell/stroma boundaries or diffusely throughout stroma, a substantial proportion of lobular carcinomas (12/18) had very little (P less than 0.001). This difference could not be related to differences in laminin immunoreactivity, which was most commonly scanty or absent in both tumour types. It is postulated that the characteristic infiltration pattern of lobular carcinoma may be attributed in part to paucity of stromal fibronectin.     

Histologic variants of infiltrating lobular carcinoma of the breast.

Thirty-eight breasts with lobular carcinoma in situ and an additional intraductal or infiltrating cancer were studied. Twenty-six of the additional cancers were diagnosed as infiltrating lobular cancer on the basis of a single population of small uniform cells cytologically identical to those in lobular carcinoma in situ. In 20 of these cases the conventional pattern of infiltrating lobular cancer was evident with an individual cell infiltrate with foci of single filing. In the other six there was a confluent arrangement of cells in solid sheets. This pattern has not been previously reported as a pattern of infiltrating lobular cancer. Because of the identical cytologic appearance, we believe it is a variant of infiltraing lobular cancer and should be diagnosed as such.     

E-cadherin expression in pleomorphic lobular carcinoma: an aid to differentiation from ductal carcinoma

Pleomorphic lobular carcinoma is a recently described entity separated from classical lobular carcinoma by cytologic pleomorphism. It can have an aggressive clinical course with a higher frequency of recurrence. Histologic differentiation with ductal carcinoma may be difficult, but it is important for this differentiation to be made. E-cadherin is a transmembrane glycoprotein, and complete loss of E-cadherin expression has been observed in invasive lobular carcinoma and lobular carcinoma in situ. Ductal carcinoma retains at least some expression of E-cadherin. We examined the pattern of E-cadherin expression in a series of 14 cases of pleomorphic lobular carcinoma by immunohistochemistry. Twelve of the 14 cases showed no staining (86%); the remaining two cases exhibited 10% to 25% positive cells. In cases with histologic equivocal features, immunohistochemical detection of E-cadherin expression can be a useful diagnostic aid for the differentiation of pleomorphic lobular and ductal carcinoma.     

Tubular carcinoma: a variant of secretory breast carcinoma

Fifteen cases of tubular carcinoma of the breast have been studied using histochemical methods for mucosubstances, immunocytochemical methods for casein and actin and conventional electron microscopy. Mucosubstances and casein were demonstrated lying freely in the lumina of the tubules. Occasionally, mucosubstances and casein assumed the form of target-like intracytoplasmic 'inclusions' like those characteristically seen in lobular carcinoma. The neoplastic cells did not react with antisera specific against actin. Even at ultrastructural level no myoepithelial cells were observed, whilst villi were revealed along the tubular luminal surface. It appears that, in addition to distinctive biological, histological and ultrastructural features, tubular carcinoma has an almost constant histochemical pattern. This suggests a differentiation towards epithelial secretory cells engaged in intensive milk protein production which has also been shown to be a feature of lobular carcinoma. It is concluded that though lobular carcinoma and tubular carcinoma of the breast have been traditionally regarded as two distinct entities, they have certain similar functional characteristics and it is postulated that these two tumours could represent the extreme variants fo the same entity: the infiltrative lobular carcinoma being the most undifferentiated and tubular carcinoma the most highly differentiated.     

Transitional cell carcinoma of the bladder mimicking lobular carcinoma of the breast: a discohesive variant of urothelial carcinoma

AIMS: To describe a series of 10 cases of transitional cell carcinoma which show morphological features which mimic lobular carcinoma of the breast and diffuse carcinoma of the stomach. METHODS AND RESULTS: Ten cases were identified from the files at Southampton University Hospitals NHS Trust and from the authors' consultation files. Immunostains were performed and clinical information was obtained. Eight of the patients were male and two female. Ages ranged from 52 to 77 years at presentation. All of the tumours showed areas where the tumour was composed of uniform cells with a discohesive single-cell, diffusely invasive growth pattern. In areas the tumour cells were arranged in linear single-cell files and in separate areas solid sheets of discohesive cells. In all of the cases some tumour cells showed prominent intracytoplasmic vacuoles. In addition to this pattern, four cases showed typical transitional cell carcinoma or carcinoma in situ. The majority of the tumours expressed cytokeratin 20 but not oestrogen receptors. CONCLUSION: This study highlights a pattern of diffusely invasive transitional cell carcinoma not previously described and one which is important to recognize in order to avoid misdiagnosis of metastatic lobular carcinoma of the breast, especially in small biopsies.     

Pleomorphic lobular carcinoma in pleural fluid: diagnostic pitfall for atypical mesothelial cells

Pleomorphic lobular carcinoma (PLC) is a subtype of infiltrating lobular carcinoma because of its dyscohesiveness, linear infiltration pattern, and lack of membranous E-cadherin staining. However, it differs from classic lobular carcinoma because of its high-grade cytology and more aggressive clinical behavior. In breast fine-needle aspiration biopsies, PLC can be confused with invasive ductal carcinoma, particularly the apocrine variant. In this report, we illustrate how metastatic PLC in body fluid specimens shows many of the same cytomorphologic changes that occur in reactive/atypical mesothelial cells. Fortunately, the immunohistochemical staining pattern of PLC can help to distinguish it from other possible diagnoses in the differential, such as reactive/atypical mesothelial cells and other metastatic neoplasms. However, the frequent apocrine features seen in this variant of breast carcinoma can cause nonspecific immunohistochemical positivity that may make the interpretation difficult. This is the first report illustrating the cytopathology and immunohistochemical findings of pleomorphic lobular carcinoma in body cavity fluid cytology. Our case highlights the important issues and pitfalls to be aware of when making this diagnosis.     

Lobular carcinoma of the breast: a special variant of mucin-secreting carcinoma.

There is currently much speculation over the precise nature of lobular carcinoma in-situ of the breast and its significance. Histochemical study shows that it is rich in sialomucin. This has a characteristic intracellular distribution which distinghishes lobular carcinoma in-situ from cancerization of lobules. The same histochemical features are seen in the infiltrative phase of the tumour. These findings invalidate the concept that it is a myoepithelial-cell tumour. Practical applications of the distinctive pattern of mucin secretion are discussed.     

Lymphoepithelioma-like carcinoma of the breast

Lymphoepithelioma-like carcinoma (LELC) of the breast is a rare, newly recognized subtype of breast carcinoma. Distinction from medullary carcinoma is important because of the difference in biologic behavior of these two neoplasms and LELC of the breast is regarded as an unusual form of lobular carcinoma. We present the case of a 56-year-old female with a breast mass measuring 2 cm in diameter, which was diagnosed as invasive lobular carcinoma with LELC pattern. This is the ninth case reported in the English literature and to the best of our knowledge the first one with lymph node metastasis.     

Histopathological and clonal study of combined lobular and ductal carcinoma of the breast

Lobular carcinoma in situ (LCIS) clinically constitutes a risk factor for the subsequent development of either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). In order to approach the possibility of this common precursor of both ILC and IDC, we investigated combined lobular and ductal carcinomas. Thirty‐two cases of lobular carcinoma were picked up out of 773 cases of operated breast carcinomas. The histopathological detailed re‐examination using immunostain of E‐cadherin and β‐catenin revealed a rather high frequency of combined lobular carcinomas than previous reports. Clinicopathologically, combined lobular carcinomas were younger and smaller than pure lobular carcinomas, and the cytological atypia was relatively low. These results suggested that combined lobular carcinomas could be detected in the earlier stage of breast cancer. Furthermore, the lobular and ductal components of combined carcinomas coexisted in the neighborhood and were distributed contiguously. The immunohistochemical phenotypes of both components were accorded in most combined cases. A genetic analysis using methylation‐specific PCR on the HUMARA gene demonstrated that the same allele was inactivated in both lobular and ductal components in all detectable cases of combined carcinoma. Therefore, it is reasonable to assume that both lobular and ductal components of combined carcinomas are clonal and derived from the LCIS as the common precursor lesion, which may contradict the conventional concept that the lobular and ductal carcinomas arise from distinct differentiation pathways.     

Cytokeratin 8 immunostaining pattern and E-cadherin expression distinguish lobular from ductal breast carcinoma

Immunohistochemistry using antibodies to cytokeratin 8 can serve as a valuable diagnostic tool for the differentiation of lobular from ductal carcinomas of the breast. In contrast with ductal carcinomas, which exhibit a peripheral-predominant immunostaining pattern, adjacent tumor cells "molding" to each other, lobular carcinomas exhibit a ring-like perinuclear immunostaining pattern, creating a "bag of marbles" appearance with neighboring tumor cells. This immunostaining pattern is stable even in the tumors that otherwise do not exhibit characteristic histomorphologic features (i.e., solid or pleomorphic type of a lobular carcinoma) and tumors that mimic growth patterns characteristic of the respective other tumor type (i.e., targetoid or single-file growth pattern in a ductal carcinoma). Furthermore, we demonstrate that ductal carcinomas express E-cadherin in a similar peripheral-predominant immunostaining pattern (33/33 cases), while all 15 lobular carcinomas were negative for E-cadherin, suggesting a role for E-cadherin in the architectural organization of the cytoskeletal scaffolding within the tumor cells.     

Histiocytoid breast carcinoma: an apocrine variant of lobular carcinoma

Two cases of in situ and invasive histiocytoid breast carcinoma are described. The invasive components of both tumours showed architectural and cytological similarities to lobular carcinoma. The in situ components showed areas of classical lobular carcinoma in situ, areas of lobular carcinoma with apocrine features and areas with transitional features. It is concluded that histiocytoid carcinoma represents an apocrine variant of lobular carcinoma. Differentiation of this tumour from chronic sclerosing inflammation may be difficult in both primary and secondary lesions.     

Signet-ring cell carcinoma of the breast

Primary signet-ring cell carcinoma of the breast is a very rare tumor and is not recognized as an independent entity of the World Health Organization classification of breast tumor. Primary signet-ring cell carcinoma of the breast is usually considered as a variant of mucinous carcinoma or lobular carcinoma and usually originates from the lobular epithelium. A case of primary signet-ring cell carcinoma of the breast in a 68-year-old woman is presented. Histologically, the majority of neoplastic cells had an intracytoplasmic mucin collection. The histological presence of ductal carcinoma in situ, absence of lobular lesion and immunoreactivity for estrogen and progesterone receptors implicated the tumor cells arising from ductal epithelium. The papillary or organoid growth pattern is characteristic in this case. The patient underwent a modified radical mastectomy and was subsequently followed up for 6 months.     

Matrix metalloproteinase-11 overexpressed in lobular carcinoma cells of the breast promotes anoikis resistance

The purpose of the present study was to examine the pathobiological properties of a matrix metalloproteinase, MMP-11 (also known as stromelysin-3), in the carcinogenesis of lobular carcinoma of the breast. Immunohistochemical staining demonstrated immunoreactivity with specific antibody to MMP-11 in 16 of 30 lobular carcinoma cells, but not in the non-cancerous terminal duct lobular unit. In positive cases, both noninvasive and invasive cancer cells exhibited immunoreactivity with anti-MMP-11 antibody; however, the staining patterns in noninvasive and invasive foci were distinct. In the noninvasive foci, immunoreactivity was observed in the cytoplasm beneath the plasma membrane, whereas immunoreactivity was found in all of the cytoplasm of infiltrating lobular carcinoma cells. Enforced expression of MMP-11 in the cultured lobular carcinoma MDA-MB-330 cells did not affect cell growth or Matrigel invasion activity. By contrast, overexpression of MMP-11 significantly increased resistance to anoikis, a programmed cell death triggered by a lack of proper cell matrix interaction, as evidenced by decrease in annexin V-positive cells and apoptotic DNA ladders. The present findings indicate that MMP-11 is overexpressed in many lobular carcinoma cells and that it may play a role in lobular carcinogenesis through increasing resistance to anoikis.     

E-cadherin immunohistochemical analysis of histiocytoid carcinoma of the breast

Histiocytoid carcinoma is a rare type of invasive breast carcinoma. It has been considered to be a variant of lobular carcinoma, a variant of apocrine ductal carcinoma, and an apocrine variant of lobular carcinoma and to resemble lipid-rich carcinoma. In attempts to elucidate its histogenesis, investigators have used mucin and oil red O histochemical analysis and GCDFP-15 immunostaining. E-cadherin is a relatively recent addition to the armamentarium of immunohistochemical markers used for cell differentiation and is a member of a family of transmembrane glycoproteins that has been shown to have a strong correlation with the histologic phenotypes of breast carcinoma. Most ductal carcinomas show diffuse membrane expression of E-cadherin, and lobular carcinomas are characterized by complete lack of membrane staining of E-cadherin. The object of this study was to use E-cadherin immunohistochemical analysis to help clarify the histogenesis of histiocytoid carcinoma. Fourteen cases containing the diagnosis of histiocytoid carcinoma of the breast were identified at M. D. Anderson Cancer Center (Houston, TX) from 1988 to 2001. All cases were rereviewed, histologic features were evaluated, and immunohistochemical staining with E-cadherin and GCDFP-15 was performed. Clinical information was extracted from the patients' medical records. Eleven cases met published histologic criteria for histiocytoid carcinoma. The remaining three cases were apocrine carcinoma. The pattern of tumor infiltration was solid, without secondary lumen formation in all cases of histiocytoid carcinoma. Lobular carcinoma in situ was identified in eight cases, but was absent in three. There was no E-cadherin immunohistochemical staining in eight of the 11 cases of histiocytoid carcinoma (72.7%). GCDFP-15 was immunoreactive in all 10 cases of histiocytoid carcinoma where it was performed. Follow-up data was available for nine of the 11 cases of histiocytoid carcinoma: six patients were alive with disease at 1.5 to 48 months, one patient had died of disease at 60 months, and two patients had no evidence of disease at 32 and 45 months. We conclude that histiocytoid carcinoma has an immunophenotypical profile consistent with both ductal and lobular differentiation. Moreover, the lack of consistent morphologic features, a specific clinical profile, and a distinct immunohistochemical pattern lead us to hypothesize that histiocytoid carcinoma is not a special type of breast cancer.     

Morpho-functional differentiation in lobular carcinoma of the breast

Lobular carcinoma of the breast has been studied using histochemical methods for mucosubstances; immunocytochemical methods for casein and actin; the ruthenium red electronycytochemical method for acid glycoproteins and an immunoelectroncytochemical method for casein. Mucosubstances and casein showed a similar cytoplasmic localization, but casein production was much more intense and also showed a more diffuse cytoplasmic localization. Occasionally casein assumed the form of target-like 'inclusions' as seen characteristically with the mucosubstances. The neoplastic cells were not stained by antisera against actin. Ultrastructurally, some cells showed an intracytoplasmic lumen with microvilli and/or an irregular outline at one extremity which was covered by microvilli. An electron-dense 'fuzz' and casein coated the microvilli of cells exposed respectively to ruthenium red and an anticasein serum followed by peroxidase--anti-peroxidase complexes. It is concluded that lobular carcinoma shows evidence of epithelial rather than myoepithelial differentiation with the emphasis on epithelial secretory cells engaged in intensive milk protein production. All 10 tumours tested for oestrogen receptors were positive in contradistinction to ductal carcinoma with a lower incidence of positivity. It appears that, in addition to distinctive histological and histochemical features, lobular carcinoma has an almost constant endocrine pattern in respect of its oestrogen receptor content.     

Lobular neoplasia in breast core needle biopsy specimens is not associated with an increased risk of ductal carcinoma in situ or invasive carcinoma

Recent reports suggest that the finding of lobular neoplasia (atypical lobular hyperplasia [ALH] or bular carcinoma in situ [LCIS]) in breast core needle biopsy specimens may be associated with an increased risk of both ductal carcinoma in situ (DCIS) or invasive carcinoma at excision. We reviewed our breast core biopsy material to see if we could confirm this finding. from 4,297 biopsies, 71 cases of lobular neoplasia lone and 35 cases of lobular neoplasia associated with typical ductal hyperplasia were identified. Biopsy follow-up revealed DCIS or invasive carcinoma in none of 6 cases of ALH, none of 9 cases of LCIS, and DCIS in 1 of 11 cases with both atypical ductal hyperplasia and LCIS. Our results suggest that patients with lobular eoplasia in breast core biopsy specimens are not at increased risk of either DCIS or invasive carcinoma at excision, and patients with this finding and no other linical or pathologic indications for biopsy can be llowed up rather than routinely undergo excision.     

Lobular carcinoma in situ diagnosed by core needle biopsy: when should it be excised?

Core needle biopsy is the preferred technique for evaluating breast masses and abnormal mammographic findings. The frequency of detection of noninvasive lobular lesions by core needle biopsy is increasing. Historically, the diagnosis of lobular carcinoma in situ has been considered a risk factor for the development of invasive carcinoma, and treatment has consisted of careful clinical follow-up with or without chemopreventive therapeutic agents such as tamoxifen citrate. We retrospectively reviewed core needle biopsy material with the primary diagnoses of lobular carcinoma in situ, atypical lobular hyperplasia, and lobular neoplasia in conjunction with clinical and radiographic findings to make recommendations as to when excision may be merited. We searched our database for core needle biopsy cases with lobular carcinoma in situ, atypical lobular hyperplasia, and lobular neoplasia as the primary diagnosis. Microcalcifications had been sampled with a stereotactically guided, 11 G Mammotome biopsy device, and masses had been sampled with an ultrasound guided, 18 G core needle. Glass slides were reviewed and histological parameters assessed. Mammographic findings were reviewed, and clinical information was obtained from the medical record. When available, excisional biopsy material was reviewed. The 2337 breast core needle biopsies performed from January 1995 to December 2001 included 35 (1.5%) with classic lobular carcinoma in situ (14), lobular neoplasia (4), and atypical lobular hyperplasia (17) as the primary diagnosis. Twelve of these 35 cases (34%) had histological evidence of microcalcifications directly associated with the lobular carcinoma in situ, lobular neoplasia, atypical lobular hyperplasia. Radiologic review revealed 21 calcifications, 6 ultrasonographic masses, and 8 mammographic masses and/or architectural distortions. Excisional biopsy had been performed in 17 cases (49%). In six cases diagnosed as in situ on core needle biopsy, excisional biopsy revealed invasive carcinoma. All of these patients had radiographically detectable masses. Eleven cases had excisional biopsies that showed histology similar to that of the core needle biopsies. The most important predictor of invasive carcinoma on excision was a synchronous mass lesion. Lobular carcinoma in situ involving adenosis and lobular carcinoma in situ with pagetoid spread on core needle biopsies did not show a histologically more aggressive lesion on excision and, therefore, may not require additional surgery. Histologically identified calcifications were associated with lobular lesions 34% of the time; however, their presence inside an in situ lobular lesion did not portend worse pathology on re-excision and should not be a criterion for excision. Based on these findings, we recommend excisional biopsy of lobular carcinoma in situ, atypical lobular hyperplasia or lobular neoplasia only when it is associated with a synchronous mass lesion.     

Invasive lobular carcinoma of the breast. An analysis of 29 cases

Twenty-nine cases of invasive lobular carcinoma were analyzed, based on three aspects of the histology: 1) cellular features such as a monotonous proliferation of uniform small cells, 2) a single file or targetoid arrangement, and 3) loss of cell cohesion or dissociation of tumor cells. Twenty-four tumors which fulfilled these three criteria were appraised as cases of conventional lobular carcinoma, in a classic sense, while five others were a variant of this tumor. Individual tumor cells of lobular carcinoma were estimated to be well differentiated, both morphologically and functionally, revealing well developed intracytoplasmic organelles and a high percentage of alpha-lactalbumin content in the cytoplasm. Nevertheless, the tumor itself was characterized by a lack of any particular structural differentiation in the arrangement of cells. Based on the observation of the histologic features, invasive lobular carcinoma was subclassified into three groups, in situ predominant, intermediate, and diffuse infiltrating and with a definite correlation to the age of the patient and to the prognosis. Validity of this classification indicates that lobular carcinoma progresses gradually, even in the invasive phase, and can be categorized as a slowly growing subset of mammary carcinoma.     

Lobular carcinoma in situ in sclerosing adenosis

The initial presentation of breast malignancy as noninvasive carcinoma in an area of sclerosing adenosis is unusual. Especially, lobular carcinoma in situ in sclerosing adenosis sometimes can be a potential source of confusion with invasive lobular carcinoma. We report a case of lobular carcinoma in situ presenting in adenosis exhibiting patterns akin to invasive lobular carcinoma, thus leading to potential misdiagnosis. Overall architecture of the lesion as seen at lower power and immunohistochemistry can be useful to distinguish between sclerosing adenosis with lobular carcinoma in situ and infiltrating lobular carcinoma.