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Contrary to the usual distribution of lobular carcinoma in situ in a few lobules or terminal ducts, a case of disseminated lobular carcinoma is described occupying all lobules of the whole breast. The tumor developed in the left breast of a 61-year-old woman with the clinical symptoms of an increasing diffuse induration. The proliferating cells were predominantly pleomorphic with hyperchromatic nuclei and loss of cell cohesion. In 690 slides examined the tumor cells in lobules and ducts revealed various stages of proliferation with transition to invasive small cell carcinoma in 15 different areas. This disseminated lobular carcinoma appears to be an advanced form of primary cancer multicentric in one breast and originating from the basal cells of the lobules and terminal ducts due to a general carcinogenic stimulus.
AIMS: The study addresses whether pleomorphic lobular breast carcinomas represent a distinct entity with respect to proliferation and apoptosis as well the expression of the p53, bcl-2 and Her2 protein. METHODS AND RESULTS: The study included 30 cases of pleomorphic lobular carcinoma (PLC; G2 n=15, G3 n=15). Poorly differentiated invasive ductal carcinomas (IDC; n=15) and well-differentiated infiltrating lobular carcinomas (ILC; n=15) were used as controls. Lymph node metastases were present equally in all groups. MIB-1 labelling was counted as: PLC (G2) 8.36%; PLC (G3) 11.3%; IDC 44.26%; ILC 2.19% (P=0.0001, P=0.004, P=0.001). Apoptotic index was: PLC (G2) 0.82%; PLC (G3) 1.2%; IDC 2.09%; ILC 0.6% (P=0.009, P=0.001). Over-expression of Her2 protein was detected in 53% of PLC (G3) tumours and was present only in scattered cases in the other groups. PLCs and ILCs were strongly positive for bcl-2 and for hormone receptors, while p53+ cells were rare. IDCs exhibited a heterogeneous staining pattern for bcl-2 and for hormone receptors, while p53+ cells occurred considerably more frequently. Stage could not be linked directly to proliferation or apoptosis. CONCLUSION: Our data suggest that more frequent over-expression of Her2 among PLCs (G3) as well as the generally low apoptosis can contribute to their aggressive behaviour.
Forty patients undergoing breast-conserving therapy for invasive lobular carcinoma were studied for the volume of lobular carcinoma in situ (LCIS) in the surgical specimen and its relationship to the surgical margins. The pathology of all cases was reviewed for margin status as well as the volume of LCIS in the surgical specimen. Mean follow-up time was 67 months. There were no local recurrences despite the fact that 38 per cent of patients had close or involved margins. There was one cancer-related death. Increasing tumor size and moderate or extensive involvement of the surgical specimen with LCIS were found to be independent predictors of axillary node metastases. The volume of LCIS in the surgical did not appear to have an impact on local recurrence. This paper adds to the growing body of literature suggesting that in patients undergoing breast-conserving therapy, LCIS in the surgical margin does not impact the risk of local recurrence and therefore may not require reexcision for close or involved surgical margins.
BACKGROUND: Although controversy exists, invasive lobular carcinoma (ILC) differs in its high frequency of microscopically positive margins after conservative therapy compared to invasive ductal carcinoma (IDC). If ILC could be recognized by imaging modalities, it would provide important information for surgeons. We tried to confirm whether it is possible to distinguish ILC from other invasive carcinomas by ultrasonography (US). METHODS: A total of 81 histologically confirmed cases of IDC, including 26 cases of papillotubular carcinoma, 28 cases of solid-tubular carcinoma and 27 cases of scirrhous carcinoma, as well as 24 cases of ILC were selected and retrospectively studied with regard to the features of mass lesions on US examination. RESULTS: The sensitivities of US for papillotubular carcinoma, solid-tubular carcinoma, scirrhous carcinoma and ILC were 88.5%, 100%, 92.6% and 91.7% respectively. We could divide invasive breast cancer into two groups by US findings. One group had a low frequency of malignant findings and consisted of papillotubular and solid-tubular carcinomas, and the other group had a high frequency of malignant findings and consisted of scirrhous carcinomas and ILC. However, there were no statistical differences between papillotubular carcinoma and solid-tubular carcinoma or between scirrhous carcinoma and ILC with regard to the US findings. CONCLUSIONS: Scirrhous carcinoma, the most common type of IDC, and ILC are difficult to distinguish by US. Therefore it is difficult to separate ILC from IDC by US.
BACKGROUND: Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor-product relation. The possible genomic relation between synchronous LCIS and ILC was analyzed using the technique of array-based comparative genomic hybridization (CGH). METHODS: Twenty-four samples from the University of California-San Francisco pathology archives that contained synchronous LCIS and ILC were identified. Array CGH was performed using random primer-amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within synchronous LCIS and ILC were compared. RESULTS: A substantial proportion of the genome was altered in samples of both LCIS and ILC. The most frequent alterations were gain of 1q and loss of 16q, both of which usually occurred as whole-arm changes. Smaller regions of gain and loss were seen on other chromosome arms. Fourteen samples of LCIS were related more to their paired samples of ILC than to any other ILC, as demonstrated by a weighted similarity score. CONCLUSIONS: LCIS and ILC are neoplastic lesions that demonstrate a range of genomic alterations. In the current study, the genetic relation between synchronous LCIS and ILC suggested clonality in a majority of the paired specimens. These data were consistent with a progression pathway from LCIS to ILC. The authors conclude that LCIS, which is known to be a marker for an environment that is permissive of neoplasia, may itself represent a precursor to invasive carcinoma.
The histological characterization of mammary cancer (MC) is of leading importance for prognosis and choice of therapeutic methods (directed hormonal and chemotherapy). In this respect of interest is the morphological picture of a special form of MC, lobular cancer which is characterized by the most malignant course, marked infiltrative and less manifest destructive growth, multicentricity and multiplicity, as well as bilateral foci of lesions. It probably originates from the myoepithelium. In the national literature, no information on lobular MC is available. Little information is available on the precursor of lobular MC, lobular carcinoma in situ. This problem is insufficiently and inaccurately dealth with in the International classification of mammary gland tumors (WHO). A review of literature on lobular MC, as well as photomicrographs of its structure and that of its precursor are presented.
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.
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PURPOSE: Preoperative chemotherapy in patients with primary breast cancer treated with anthracyclines and taxanes results in high response rates, allowing breast conserving surgery (BCS) in patients primarily not suitable for this procedure. Pathological responses are important prognostic parameters for progression free and overall survival. We questioned the impact of histologic type invasive ductal carcinoma (IDC) versus invasive lobular carcinoma (ILC) on response to primary chemotherapy. PATIENTS AND METHODS: 161 patients with breast cancer received preoperative chemotherapy consisted of epidoxorubicin 75 mg/m(2) and docetaxel 75 mg/m(2) administered in combination with granulocyte-colony stimulating factor (G-CSF) on days 3-10 (ED + G). Pathological complete response (pCR), biological markers and type of surgery as well as progression free and overall survival were compared between IDC and ILC. RESULTS: Out of 161 patients, 124 patients presented with IDC and 37 with ILC. Patients with ILC were less likely to have a pCR (3% vs. 20%, P < 0.009) and breast conserving surgeries (51% vs. 79%, P < 0.001). Patients with ILC tended to have oestrogen receptor positive tumors (86% vs. 52%, P < 0.0001), HER 2 negative tumors (69% vs. 84%), and lower nuclear grade (nuclear grade 3, 16% vs. 46%, P < 0.001). Patients with ILC tended to have longer time to progression (TTP) (42 months vs. 26 months) and overall survival (69 months vs. 65 months). CONCLUSIONS: Our results indicate that patients with ILC achieved a lower pCR rate and ineligibility for BCS to preoperative chemotherapy, but this did not result in a survival disadvantage. Because of these results new strategies to achieve a pCR are warranted.
PURPOSE OF REVIEW: The incidence of lobular carcinoma in situ and invasive lobular carcinoma of the breast is increasing. Recent data suggest that lobular carcinoma in situ is an indolent precursor for breast cancer, rather than a pure risk factor. This could imply free surgical margins become important. The risk of contralateral carcinoma and of multifocality of invasive lobular carcinoma is higher than for invasive ductal carcinoma. Therefore, the need for mastectomy, or even for preventative contralateral mastectomy is questioned. Conventional mammography or ultrasonography cannot always give useful preoperative information about the extent of lobular cancers. The value of dynamic contrast-enhanced magnetic resonance imaging needs to be established for these patients. RECENT FINDINGS: The risk of invasive carcinoma after lobular carcinoma in situ is increased. Invasive carcinoma is usually located at the index point of lobular carcinoma in situ and is of lobular histology. Dynamic contrast-enhanced magnetic resonance imaging can be useful in the detection and preoperative staging of invasive lobular carcinoma. The risk of local recurrence is high in patients with invasive lobular carcinoma. Mastectomy and breast reconstruction could be an option in selected patients. The response to preoperative chemotherapy is worse for invasive lobular carcinoma compared with invasive ductal carcinoma, with a greater need for rescue mastectomy. SUMMARY: Lobular carcinoma in situ and invasive lobular carcinoma are different entities from ductal carcinoma in situ and invasive lobular carcinoma. Their biological profile should be studied further in order to make the fine tuning of treatment possible.
The aims of this study were twofold: (1) to evaluate the ability of pathologists to recognize infiltration of bone marrow core biopsy specimens by breast carcinoma, particularly lobular carcinoma, using routine hematoxylin-eosin (HE) sections; and (2) if indicated, to determine the reasons for difficulties in diagnosis. Thirty-six bone cores obtained before bone marrow harvest were involved by breast carcinoma and were confirmed by pancytokeratin immunostains. Thirty of the 36 were ductal carcinomas and six were lobular carcinomas. Fourteen negative bone core biopsy specimens (from patients with breast cancer or lymphoma) were included as controls. These 50 bone cores were reviewed by three surgical pathologists. Lobular carcinoma was correctly identified in only 39% of positive specimens as compared with 88% for ductal carcinoma. After instruction, sensitivity for the detection of lobular carcinoma improved to 61% but at the expense of an unacceptably high rate of false-positive diagnoses (18%). None of the three pathologists was able to achieve both high sensitivity and high specificity in recognizing lobular carcinoma in the bone marrow. Lobular carcinoma was difficult to detect because of tumor cell size similar to hematopoietic cells, infiltration as single cells, presence of bland cytological features, and paucity of tissue reaction to the tumor. Although the number of cases of bone marrow involved by lobular carcinoma is small, these findings suggest that pancytokeratin stains should be performed routinely in the evaluation of bone core biopsy specimens from patients with lobular carcinoma, and probably from patients with ductal carcinoma whose HE-stained bone core biopsy specimens are considered negative for tumor.
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Histologic examination using serial sections of a mastectomy specimen from an ILC patient with LCIS and unusual lobular proliferation showed the following: 1) Cancer cells and their infiltration patterns varied and were not typical of ILC, so that this case was categorized as ILC partially possessing some histologic features of IDC. 2) Unusual lesions of proliferation, which were initially regarded as ALH, consisted of both pure ALH and ILC invading the ALH and normal lobules. For the correct diagnosis of ALH in biopsy specimens, therefore, we must bear in mind the (possible) concomitant presence of ILC. 3) The histologic criteria for ALH and ILC must be defined more clearly.
BACKGROUND: Incidence rates of ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) have been rising, but little is known about which patients will develop invasive breast cancer or what types of tumors these patients may develop. METHODS: By using Surveillance, Epidemiology and End Results (SEER) data, the authors evaluated how types of invasive breast cancers diagnosed among 37,692 DCIS and 4490 LCIS patients differed and how clinical characteristics influenced subsequent breast cancer risk. RESULTS: Among DCIS patients, incidence rates of ipsilateral and contralateral invasive breast cancer were 5.4/1000 person-years and 4.5/1000 person-years, respectively; and among LCIS patients, incidence rates were 7.3/1000 person-years and 5.2/1000 person-years, respectively. LCIS patients were 5.3-fold more likely than DCIS patients to develop invasive lobular carcinomas. Women whose DCIS had comedo histologic features or was poorly differentiated had 1.4-fold and 2.0-fold elevations in ipsilateral invasive breast cancer risk. Furthermore, among DCIS patients, 20-49 year-olds and black women and Hispanic white women had 1.6, 2.7, and 2.3-fold elevated risks of Stage III/IV breast cancer compared with 50-59 year-olds and non-Hispanic whites, respectively. CONCLUSIONS: Screening young DCIS patients more frequently and improving the follow-up care of blacks and Hispanic whites with DCIS may reduce their risk of advanced-stage breast cancer. In addition, LCIS may be a precursor rather than just an ambiguous risk factor for invasive breast cancer, and, therefore, localized treatment for LCIS may be warranted. Given that incidence rates of DCIS and LCIS have been rising, investigations of these tumors should be continued to better understand their etiology and appropriate clinical management.
Differential diagnosis of excessive lobular calcifications of the breast can be difficult, especially if they are polymorphous in character. In those cases good cooperation between radiologist, surgeon and pathologist is of importance. We present a case in which we could find three types of noninvasive carcinomas combined with polymorphous lobular calcifications.
Invasive pleomorphic lobular carcinoma (PLC) is a distinctive aggressive subtype of invasive lobular carcinomas (ILC). We report one case of PLC with in situ PLC and ductal carcinoma in situ with apocrine features.