Invasive Pleomorphic Lobular Carcinoma Research Articles

Comparison of MRI Features of Invasive Pleomorphic and Classical Lobular Carcinoma: Differentiation Is Possible?

Comparison of MRI Features of Invasive Pleomorphic and Classical Lobular Carcinoma: Differentiation Is Possible?

Atypical Breast CarcinomaA Series of Six Cases

Breast cancer comprises 10.4% of all cancer among women world and it the second most common type of cancer. Increased public awareness and screening have led to earlier diagnosis at different stages. Surgical resection can be done earlier and complete cure of the disease can be achieved. As a result survival rates for breast cancer in young women have improved significantly. Six unusual type of breast carcinoma, presented to the Surgery Outpatient Department were referred to Pathology Department for further investigations. Patient age and sex, clinical characteristics of the tumour, the duration of the lesion, the size, radiological investigation, Fine Needle Aspiration Cytology (FNAC), trucut biopsy and histopathological examination were noted. Immunohistochemical examination also done in all the cases. Out of the six cases of breast carcinoma, one was the mucinous carcinoma of breast, two invasive papillary breast carcinoma, one apocrine carcinoma, one invasive Pleomorphic Lobular Carcinoma (PLC) of breast and one was fibromatosis like metaplastic carcinoma of breast. All the patients were female except, a 71-year-old male who presented with invasive papillary carcinoma. All the female patients were presented at postmenopausal age group. After careful examination of the cytology and histopathological slides the final diagnosis was made which helped the clinician for further treatment. Rare breast cancers do not differ from other types of breast cancer in their presentation. But they vary by treatment regimens and outcomes. So, proper diagnosis with imaging, FNAC, trucut biopsy and histopathological examination is a combined tool for proper diagnosis and treatment.

Targetable alterations in invasive pleomorphic lobular carcinoma of the breast

BackgroundInvasive pleomorphic lobular carcinoma (PLC) of the breast is a subtype of invasive lobular cancer which compromises approximately 1% of all epithelial breast malignancies and is characterized by higher nuclear pleomorphism and poorer prognosis than classic invasive lobular cancer (ILC). Since PLC is more aggressive than classical ILC, we examined the underlying molecular alterations in this subtype of breast cancer to understand the possible benefit from targeted therapies.MethodsIn this study, we investigate the clinical characteristics and molecular alterations in 16 PLC from our institution. Additionally, we examined the clinical and genomic features in 31 PLC from the Cancer Genome Atlas (TCGA).ResultsOverall, our analysis of PLC found that 28% had activating ERBB2 mutations, 21% had ERBB2 amplification, and 49% activating PIK3CA mutations. Among cases from our institution, we found 19% with activating ERBB2 mutations, 25% had ERBB2 amplification, and 38% with activating PIK3CA mutations. In data from TCGA, 32% had activating ERBB2 mutations, 19% had ERBB2 amplification, and 55% had activating PIK3CA mutations. While classic ILC in TCGA had similar percentages of PIK3CA alterations compared to PLC, activating ERBB2 alterations were exceedingly rare, with no activating ERBB2 mutations and only one case with ERBB2 amplification. Interestingly, in further examining TCGA data which included FGFR1 and PTEN, 94% of PLC had alterations in ERBB2, FGFR1, or the PI3K pathway.ConclusionsOur results show a high frequency of ERBB2 and PIK3CA alterations in PLC and suggest all PLC should be tested for potential therapeutic targeting.

Unresectable bulky chest wall recurrent breast cancer controlled with CT-guided interstitial high-dose-rate brachytherapy and external beam radiotherapy with adjuvant hormonal therapy – case report

PurposeBulky chest wall recurrence after mastectomy presents a therapeutic challenge because of high-dose of radiation required to control the disease, and its proximity to low-tolerance organs at risk. We report a case of successful computed tomography (CT)-guided high-dose-rate (HDR) salvage interstitial brachytherapy (ISBT) boost.Material and methodsA 70-year-old female initially presented with a tumor in right breast, and was treated with mastectomy and adjuvant chemotherapy, followed by hormonal therapy for 5 years without adjuvant radiotherapy. In 2018, 20 years after the initial treatment, she developed unresectable chest wall recurrence that measured 10.5 cm × 7.3 cm × 4.5 cm, with bone and parietal pleura invasion. Biopsy revealed invasive pleomorphic lobular carcinoma [estrogen receptor (ER)-positive, progesterone receptor (PR)-negative, HER2-negative]. There was no evidence of metastatic disease.ResultsThe patient underwent external beam radiotherapy (EBRT) plus ISBT. After EBRT of 50 Gy in 25 fractions was completed, CT-guided ISBT was performed as an outpatient treatment. HDR dose was 16 Gy delivered in 2 fractions with 2 implants. Dose was prescribed to gross tumor volume. ISBT plans were created using inverse planning simulated annealing (IPSA) algorithm. Gross tumor volume D90% plus EBRT dose was 82 Gy equivalent dose of 2 Gy (EQD2), assuming α/β of 4 for breast carcinoma. The patient continued on hormonal therapy. At the 30-month follow-up, the patient remains in remission. The tumor could not be detected by magnetic resonance imaging (MRI) or positron emission tomography (PET). There were no severe treatment-related complications.ConclusionsCT-guided HDR ISBT boost can be a useful modality in individualizing treatment strategies for breast cancer patients with unresectable bulky chest wall recurrence.

Multicentric Invasive Pleomorphic Lobular Carcinoma of Breast An Uncommon Histopathological Variant

Invasive Pleomorphic Lobular Carcinoma is a very rare histopathological variant of breast cancer. It constitutes less than 1% of invasive breast carcinoma .We present a 70 year female presented with lump in right breast of 10 months duration. The lump was insidious in onset, progressive in nature and was associated with gradual skin color changes. Patient was a known diabetic and was on regular treatment. On fine needle aspiration cytology showed positive for carcinoma cells. Right modified mastectomy was performed. On histopathology reported as Invasive Pleomorphic Lobular Carcinoma – Grade II with multicentric nodules. Right axillary lymph nodes with perinodal infiltration of tumor were noted. We are presenting this case for its uncommon type, clinical, histomorphological and immunohistochemistry pattern.

Pleomorphic lobular carcinoma of the breast with osteoclast-like giant cells: a case report and review of the literature

BackgroundBreast carcinoma with osteoclast-like giant cells (OGCs) is infrequent, being most reported cased described as ductal invasive carcinomas. Invasive pleomorphic lobular carcinoma (PLC) is a distinct morphological variant of invasive lobular carcinoma characterized by higher nuclear atypia and pleomorphism than the classical type. In the best of our knowledge, a PLC with OGCs has not been previously reported.Case presentationWe report the case of a 72-year-old woman presenting with a pleomorphic tumor of the left breast with a dense infiltration by OGCs and T lymphocytes with a 10:1 predominance of CD8+ over CD4+ cells. The diagnosis of a lymphoid or mesenchymal neoplasia was excluded after demonstrating keratin expression by the neoplastic cells. The absence of E-cadherin expression and the morphological features were consistent with the diagnosis PLC with OGCs. In addition, we demonstrated the deleterious mutation C.del866C in CDH1gene, but no mutations in any of the other 33 genes analyzed by next generation sequencing.ConclusionsBreast carcinoma with stromal osteoclast-like giant cells is a very rare tumor, for that reason, the use of the cytologic features and growth patterns in combination with immunohistochemically studies is mandatory for a correct diagnosis of lobular carcinoma. In addition, further studies are necessary to clarify the influence of OGCs in the prognosis of these patients.

Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report

BackgroundInvasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare.Case presentationWe report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast.ConclusionsTo the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.

Invasive Pleomorphic Lobular Histology is an Adverse Prognostic Factor on Survival in Patients with Breast Cancer

Invasive pleomorphic lobular carcinoma (IPLC) is defined to be an uncommon and different subtype of classical invasive lobular carcinoma (ILC). This special variant is characterized by significant cytological atypia and pleomorphism which differs from the cytological uniformity of ILC. IPLC has been shown to have some poor prognostic factors such as axillary node metastasis and higher histological grade which may lead to poor clinical courses including a short relapse time, increased risk of recurrence and a decreased survival. The aim of this study is to investigate the clinicopathological characteristics and prognosis of IPLC in comparison with ILC and also to evaluate if IPLC is a different clinical entity compared to ILC. A total number of 4418 breast cancer patients treated between 1996 and 2015 in Hacettepe University Cancer Institute, were retrospectively analyzed. Among 4418 patients, 210 were diagnosed with ILC and 23 patients diagnosed with pure IPLC. In this present study, clinicopathological characteristics, disease free survival (DFS) and overall survival (OS) of patients with ILC and IPLC were compared. This study design is one of the rare face to face comparison of pure IPLC and ILC. Patients with IPLC had an increased rate of higher histologic grade, extracapsular extension, lymphovascular invasion and lower percentage of hormone positivity than those of patients with ILC. During the follow-up time, IPLC group experienced 4 cases (17.3%) of recurrence, 5 cases (21.7%) of death and 2 cases (8.7%) of progression in 3 metastatic patients compared to that of 27 cases (12.9%) of recurrence, 29 cases (13,8%) of death and 14 cases (6.7%) of progression in 19 metastatic patients in the ILC group. Patients with IPLC had a worse DFS and OS duration than patients with ILC (P = 0.02 for OS, P = 0.04 for DFS). In conclusion, IPLC is a different and a special breast cancer subtype. This study suggests that IPLC is a distinct clinical entity with an advanced stage and more aggressive clinical course. Patients with IPLC reveal poorer prognostic factors such as higher histological grade, relative lower percentages of hormone positivity, and increased rate of recurrences resulting in poor clinical outcomes and worse survival. Nowadays, it is observed that current treatment methods for IPLC do not seem as successful as in ILC and failed to be effective. Thence, individual therapies including more aggressive surgery and adjuvant or neoadjuvant chemotherapy even in the earlier stages of breast cancer should be performed for this distinct variant.

Abstract P1-01-10: Pleomorphic lobular carcinoma in situ (PLCIS)-presentation, associated lesions and outcome

Abstract Pleomorphic lobular carcinoma in situ (PLCIS) is an uncommon lesion characterised by dyscohesive lobular cells showing high grade nuclei. It is commonly associated with comedo necrosis and luminal calcifications and hence diagnosed on mammographic screening. Data on the presentation, focality, associated lesions, optimal treatment and outcome of PLCIS is patchy. Methods Cases diagnosed as PLCIS between 2005 and 2015 were identified from the imaging and pathology databases of two UK large breast screening units. Cases diagnosed on diagnostic core biopsy/VAB or surgical excisions were included. Comprehensive data was collected on age, mode of presentation (screening vs symptomatic), imaging (mammography, ultrasound and MRI), surgical management, histological features on core biopsy and excision including type, grade and immunohistochemical profile of associated ductal carcinoma in situ (DCIS) and invasive carcinoma. Results 86 cases with the diagnosis of PLCIS (confirmed by review and e-cadherin negativity) were identified. The mean patient age at diagnosis was 61.04 years, range: 39-84 years. 32 cases were treated with wide local excision with/without axillary procedure. A total of 38 patients were screen detected & 36 cases were diagnosed in the symptomatic setting. Others presented as incidental calcifications on family history screening, incidental histological findings in breast reductions and risk reducing mastectomy. On mammography, 6 patients presented with an asymmetrical density, with or without calcifications, 25 with calcifications, 44 as a mass and 2 as stromal deformity. No mammographic abnormality was found in 9 cases. PLCIS was multifocal in 19.7% of cases, diffuse in 9.9%, focal in 69% and multi-centric in 1.4% on imaging. Histologically, PLCIS was the most advanced lesion on core biopsy without associated DCIS or invasive disease (pure PLCIS) in 23 patients. Of these, surgical excision revealed an invasive carcinoma in 7 cases (upgrade rate =30.4%). Six more patients presented as DCIS and PLCIS on core biopsy; three of whom (50%) had invasive disease on excision. Classical LCIS was associated with PLCIS in 27/86 cases (31.3%). The most common type of associated invasive carcinoma on surgical excision was invasive classical lobular carcinoma (ILC, 40 cases), followed by invasive pleomorphic lobular carcinoma (IPLC, 27 cases). Ductal no special type carcinoma, solid papillary and tubulo-lobular carcinoma were also identified. The size of PLCIS on excision ranged from 1-80mm. DCIS was associated in 26.7% of cases. The majority of invasive cancers were of grade 2 (53.5%) and 3 (19%). The tumors were ER positive (53 cases), PR positive (43 cases) and HER2 negative (52 cases). Conclusion PLCIS is an uncommon in situ carcinoma presenting via mammographic and also in the symptomatic setting. Unlike classical LCIS, PLCIS is a disease of postmenopausal women. It is multifocal in approximately one fifth of the cases. PLCIS is commonly associated with classical LCIS and both ILC and IPLC. When identified in core biopsy, the upgrade rate in this series was 30.4% which increased to 50% if the lesion co-existed with DCIS. The associated cancers are often ER positive, HER2 negative. These findings support managing those lesions surgically as per DCIS. Citation Format: Shaaban AM, Smith S, Bradley S, McMahon M, Sharma N. Pleomorphic lobular carcinoma in situ (PLCIS)-presentation, associated lesions and outcome. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-01-10.

Uroplakin II Expression in Breast Carcinomas Showing Apocrine Differentiation: Putting Some Emphasis on Invasive Pleomorphic Lobular Carcinoma as a Potential Mimic of Urothelial Carcinoma at Metastatic Sites.

Uroplakin II antibody is exclusively specific for urothelial carcinoma. Nonurothelial carcinoma has not been reported to be immunoreactive for uroplakin II. In the present study, we hypothesized that breast carcinoma showing apocrine differentiation, such as invasive pleomorphic lobular carcinoma (IPLC) and apocrine carcinoma (AC), stains positive for uroplakin II. We identified 6 cases of IPLC between 2000 and 2014 by searching a computerized pathological database. We randomly selected 10 cases of each classic invasive lobular carcinoma (cILC) and AC and five cases of apocrine metaplasia (AM) that coexisted in a surgically resected breast carcinoma specimen. Immunohistochemistry was performed for uroplakin II, GATA3, CK7, CK20, and other representative markers positive for urothelial carcinoma. All cases of IPLC, AC, and AM, except those of cILC, showed immunoreactivity for uroplakin II. Poorly differentiated urothelial carcinoma sometimes shows similar morphology to IPLC with the following immunophenotype: CK7+, CK20−, GATA3+, and uroplakin II+. In the present study, this immunophenotype was observed in all the cases of IPLC and AC. Therefore, when studying metastatic, poorly differentiated carcinoma showing the aforementioned immunophenotype, we should consider the possibility of it being IPLC in addition to metastatic urothelial carcinoma.

Abstract P6-06-04: p53 and p16 as Modifiers of HERV-K in Invasive Pleomorphic Lobular Carcinoma and Classic Lobular Carcinoma of Breast

Abstract Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-06-04.

Cytohistological and immunohistochemical features of a mammary invasive pleomorphic lobular carcinoma in a dog

Departamento de Patologia, Faculdade de Medicina de Botucatu Universidade Estadual Paulista (UNESP), Distrito de Rubiao Jr., s/n Botucatu, Sao Paulo 18618-970

Invasive Pleomorphic Lobular Carcinoma of the Breast: Clinicopathologic Characteristics and Prognosis Compared with Invasive Ductal Carcinoma

PurposeInvasive pleomorphic lobular carcinoma (IPLC) is a very rare and distinct morphological variant of invasive lobular carcinoma (ILC), characterized by nuclear atypia and pleomorphism contrasted with the cytologic uniformity of ILC. This study evaluated clinicopathologic characteristics and prognosis of IPLC compared with invasive ductal carcinoma (IDC).MethodsWe retrospectively reviewed the medical records of 35 patients with IPLC and 6,184 patients with IDC, not otherwise specified. We compared the clinicopathologic characteristics, relapse-free survival (RFS) and disease specific survival (DSS) of patients who were surgically treated between January 1997 and December 2010.ResultsPatients with IPLC presented at an older age with larger tumor size, worse histologic grade, higher rates of N3 stage, more multifocal/multicentric tumors, and more nipple-areolar complex involvement than those of patients with IDC. During the follow-up period, the IPLC group experienced five cases (14.3%) of disease recurrence and three cases (8.6%) of disease specific mortality compared with 637 cases (10.4%) of recurrence and 333 cases (5.4%) of disease specific mortality in the IDC group. Univariate analysis using the Kaplan-Meier method revealed that the IPLC group showed a significantly poorer prognosis than that of the IDC group (RFS, p=0.008; DSS, p<0.001). However, after adjusting for clinicopathologic factors, a multivariate analysis showed no statistical differences in RFS (p=0.396) and DSS (p=0.168) between the IPLC and the IDC groups.ConclusionOur data suggest that patients with IPLC present with poor prognostic factors such as large tumor size, poor histologic grade and advanced stage at diagnosis. These aggressive clinicopathologic characteristics may result in poor clinical outcomes. Although our study could not link IPLC histology to poor prognosis, considering the aggressive characteristics of IPLC, early detection and considerate treatment, including proper surgical and adjuvant intervention, could be helpful for disease progression and survival.

Pleomorphic variant of lobular carcinoma breast: A rare case report with review of the literature

Pleomorphic carcinoma is a poorly described entity whose phenotype is not well recognized as within the morphological spectrum of breast carcinoma. The purpose of this report is to describe the clinicopathological features of this tumour with review of the literature. We report a case of invasive pleomorphic lobular carcinoma with coexisting classic lobular carcinoma in situ.

Clinicopathologic and biomarker analysis of invasive pleomorphic lobular carcinoma as compared with invasive classic lobular carcinoma: an experience in our institution and review of the literature

Pleomorphic lobular carcinoma (PLC) is a distinct morphological variant of invasive lobular carcinoma (ILC). Although PLC retains the distinctive loosely cohesive and single-file growth pattern of ILC, it has specific distinguishable characteristics, including enlarged nuclei with greater nuclear irregularity, increased hyperchromasia, prominent nucleoli, increased mitotic activity, and abundant eosinophilic cytoplasm. We compared the clinicopathologic features and biomarker expression of PLC and ILC. Fifty-eight cases of classic ILC (5.3%) and 7 cases of PLC (0.6%) were identified from our file between January 2002 and December 2010. Histopathologic data and tumor biomarkers were recorded. Clinical follow-up information (3-93 months; median, 29 months) for distant metastasis and survival was also gathered. Fisher exact test was used, and results were considered statistically significant if P value is less than .05. Our results showed that compared with classic ILC, PLC was more frequently grade III (P < .01), estrogen receptor negative (P < .001), and has Ki-67 greater than 10% (P < .002). In conclusion, PLC is more frequently higher grade and may exhibit an adverse biomarker profile (negative estrogen receptor and high Ki-67) as compared with classic ILC. However, no significant differences were found between PLC and classic ILC for axillary lymph node/distant metastases and survival.

Multifocal matrix-producing mammary carcinoma mimicking lobular carcinoma on core biopsy – A case with long survival reported

We report the clinico-pathologic features of a patient with extensive multifocal matrix-producing mammary carcinoma which mimicked invasive pleomorphic lobular carcinoma on biopsy. Neoplastic cells both in areas with and without matrix were positive for EMA and vimentin. Cytokeratin antibodies were negative, and there was no immunoreactivity for ER, PR, HER2, CD10, GCDF15, p63, or E-cadherin. The proliferative activity was low (<5%) in areas both with and without matrix production. Despite significant tumor volume and high-grade histologic features, an 8-year follow-up has been uneventful.

Pleomorphic ductal carcinoma of the breast: predictors of decreased overall survival.

The World Health Organization classification of tumors of the breast includes a rare variant of invasive ductal carcinoma termed pleomorphic carcinoma. This variant has marked nuclear pleomorphism (>6-fold variation in nuclear size by definition, but often>10-fold) and characteristically contains multinucleated tumor giant cells. Approximately one-third of the cases in the initial series contained a focal spindle cell metaplastic component. The tumors are reported to have an aggressive behavior, but because some contain a spindle cell metaplastic component, it is unclear whether the metaplastic component or other clinicopathologic features account for the poor clinical outcome. We identified 37 cases of pleomorphic carcinoma of the breast and evaluated the association between clinical outcome and multiple clinicopathologic features. Patients with invasive pleomorphic lobular carcinoma and those without at least a tissue biopsy before chemotherapy were excluded. Patients ranged in age from 23 to 78 years (median, 49 y). Tumor size was >5 cm in 12 cases and <5 cm in 22. A focal spindle cell component (<25% of the tumor) was present in 14 tumors (38%). Clinical follow-up was available for 36 patients (median, 17 mo). In multivariate analysis, when the 2 stage-IV patients were excluded, the presence of a spindle cell component and tumor size >5 cm were each independently associated with decreased overall survival. The actuarial 5-year overall survival for patients with and without a metaplastic spindle cell component was 38%+/-15% and 89%+/-7%, respectively. Poor clinical outcome, therefore, is associated with the subset of pleomorphic carcinomas with a spindle cell metaplastic component. As the morphologic features of pleomorphic carcinoma can be seen in primary tumors from other sites, it is important to recognize this tumor as a rare variant of invasive breast carcinoma.

Pleomorphic lobular carcinoma of the breast: a non-evident diagnosis: case report and reviewof the literature

We report a case of a 27-years-old woman with a lesion at the right breast, incidentally noted. The patient underwent tumour resection followed by a right mastectomy type “Patey”. Microscopic analysis of the tumour had recognised an invasive pleomorphic lobular carcinoma. Invasive pleomorphic lobular carcinoma (PLC) is a distinctive aggressive subtype of invasive lobular carcinomas (ILC). It has the typical infiltrating pattern of classical ILC of diffuse single cell spread but the nuclei aremore pleomorphic. Histological differential diagnosis with ductal carcinoma may be difficult, but it is important for this difference to be done. E-cadherine is a trans-membrane glycoprotein, typically expressed in ductal carcinoma, and loss of E-cadherine expression characterises invasive and in situ lobular carcinoma.

In situ and invasive lobular neoplasia of the breast

Lobular neoplasia of the breast represents a group of related malignancies with clinical implications ranging from risk lesions [atypical lobular hyperplasia and lobular carcinoma in situ (LCIS)] through to aggressive invasive lesions, notably invasive pleomorphic lobular carcinoma. The diversity in lobular carcinoma is evident at the morphological level, at the molecular marker level and in cytogenetic profiles. Research in these areas is already changing the face of the disease group, for example suggesting that some lobular and ductal carcinomas are closely related and even that one of the lobular group, the tubulo-lobular carcinomas, should, in fact, be regarded as a ductal cancer. More research is required to understand the long-term pathogenic implications of a diagnosis of in situ lobular neoplasia, particularly pleomorphic LCIS, and to understand the genetics behind the well-recognized high risk of bilateral disease. For invasive carcinoma, molecular studies will allow refinement of therapy and the possibility of novel targeted therapies, for example directed against fibroblast growth factor receptor 1.

Clinical, Histopathologic, and Biologic Features of Pleomorphic Lobular (Ductal-Lobular) Carcinoma In Situ of the Breast: A Report of 24 Cases

We reviewed 10 cases of pleomorphic lobular (ductal lobular) carcinoma in situ (PL/DLCIS) of the breast and compared them with 14 cases of pleomorphic lobular carcinoma in situ (PLCIS) found in association with invasive pleomorphic lobular carcinoma. The histologic features; immunohistochemical staining for estrogen receptors (ERs), p53, Ki67, E-cadherin, and gross cystic disease fluid protein-15 (GCDFP-15); and results of fluorescence in situ hybridization for HER-2/neu gene amplification were evaluated in all 24 cases. Histologically, PL/DLCIS cells were similar to those of PLCIS with invasion in that they were discohesive and medium to large in size with moderate to marked nuclear pleomorphism, small to prominent nucleoli, and moderate to abundant eosinophilic or vacuolated cytoplasm. In both groups, central necrosis was present in a small number of cases, and classic LCIS coexisted with the in situ lesion in less than half of the cases; in situ carcinomas were positive for ERs in 23 (100%) of 23 cases, p53 in 6 (25%) of 24 cases, and GCDFP-15 in 14 (74%) of 19 cases. The percentage of Ki67-positive tumor nuclei indicated moderate to high (more than 20%) proliferative activity in 8 (47%) of 17 cases. Immunostaining for E-cadherin was negative in all 24 cases. HER-2/neu gene amplification was observed in 1 (4%) of 23 cases. In cases with associated invasion, PLCIS had cytologic features and immunostaining patterns similar to those of the invasive pleomorphic component. Seven of the 10 patients who had PL/DLCIS without invasion underwent lumpectomy or simple mastectomy. Six of these patients had no evidence of disease in follow-up periods ranging from 4 to 32 months; the seventh patient developed recurrent disease 12 months after undergoing lumpectomy. We conclude that the cytologic features and biomarker expression profile of PL/DLCIS are similar to those of PLCIS with invasion but somewhat different from those of classic LCIS and ductal carcinoma in situ. Long-term follow-up studies are needed to further define the natural history of PL/DLCIS and its optimal management.