Breast
Noninvasive lobular neoplasia
LCIS pleomorphic
Author: Sucheta Srivastava, M.D.
Editorial Board Member: Emily S. Reisenbichler, M.D.
Last author update: 1 November 2017
Last staff update: 3 February 2023 (update in progress)
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Pleomorphic lobular carcinoma in situ "PLCIS"
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Clinical features | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Srivastava S. LCIS pleomorphic. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantpleolcis.html. Accessed June 2nd, 2023.
Definition / general
- Lobulocentric proliferation of cells which are significantly pleomorphic and large when compared to classic LCIS
Essential features
- Cytological features resemble high grade DCIS rather than
classic LCIS
- Marked acinar expansion
- Cellular dyshesion
- Abundant, dense eosinophilic cytoplasm
- Large nuclei (≥ 4x larger than a lymphocyte)
- Pleomorphism: 2 - 3x variation in nuclear size and shape
ICD coding
Epidemiology
- Initially described in 1996 by A.R. Frost (AJSP: Reviews & Reports 1996:27, Oncol Lett 2016;12:4863)
- Incidence of PLCIS is estimated to be between 2.7 - 4.4% of lobular neoplasia; however, the prevalence may be higher given the similarities of PLCIS to DCIS and probable misdiagnoses as such in the past (Ann Surg Oncol 2015;22:4263, Histopathology 2014;64:981)
- More common in postmenopausal women (Histopathology 2014;64:981)
- Tend to be older than classic LCIS
- Average age reported is 52 - 55 years
- In a study of 24 cases, ages were 36 - 86 years (mean, 55.1 years)(Mod Pathol 2002;15:1044)
- In another study of 47 cases, ages were 44 - 59 years (52.5 years mean) (Histopathology 2014;64:981)
Clinical features
- Can present with nipple discharge or mammographic mass (Histopathology 2014;64:981)
- Involves terminal ducts in postmenopausal atrophic breasts and terminal duct lobular complex in premenopausal breasts (Am J Pathol 1941;17:491)
- Patients with apocrine PLCIS tend to be older (mean age 60 years) than nonapocrine PLCIS (51 years, Am J Surg Pathol 2009;33:1683)
Radiology description
- PLCIS not associated with invasive carcinoma: abnormal microcalcifications are the most common radiological finding which can be an isolated finding or associated with architectural distortions / asymmetric density; rarely isolated finding of a spiculated mass or a nodule
- PLCIS associated with invasion: radiological finding could be a palpable mass with associated abnormal mammographic findings (architectural distortions) with or without suspicious calcifications
Prognostic factors
- Natural history of PLCIS not associated with invasive carcinoma remains largely unknown
- PLCIS may be frequently associated with invasive disease and has a more aggressive course
- Given the increased genomic instability reported for PLCIS there is speculation that the risk of subsequent breast cancer is higher than that conferred by classic LCIS
- PLCIS is considered to be a precursor of invasive cancer in addition to a marker of increased risk
- PLCIS is frequently multifocal and extensive and positive / close margins are common in the setting of breast conserving surgery
- Cases with isolated PLCIS are less likely / rarely recur compared to those associated with invasive carcinoma
- PLCIS has weaker ER expression than classic LCIS
Case reports
- Pleomorphic lobular carcinoma in situ of the breast composed almost entirely of signet ring cells (Pathol Int 2006;56:683)
Treatment
- Complete surgical excision is recommended due to high rate of upgrade following a diagnosis of PLCIS on core needle biopsy
- At surgical excision, diagnosis is upgraded to DCIS in 15 - 25% and to invasive carcinoma in 30 - 60% (Breast J 2017 Sep 19 [Epub ahead of print])
- Associated invasive carcinoma could be classic or pleomorphic invasive lobular carcinoma or invasive ductal carcinoma
- Supports that PLCIS is a risk lesion as well as a precursor lesion
- Current National Comprehensive Cancer Network (NCCN) guidelines [Accessed 17 November 2017] state that "clinicians may consider complete excision of PLCIS with negative margins" but also note that evidence on efficacy and outcomes associated with complete PLCIS excision are lacking
- Some pathologists report PLCIS margin status; if margins are close or positive, surgical re-excision or RT is discussed with the patient
- However, data is unclear, with variable reports of local recurrence after excision with positive PLCIS margin and no adjuvant RT or re-excision
- PLCIS shares some morphologic and genetic features with DCIS; however, due to small number of cases it is not clear if these patients have a risk of local recurrence similar to low, intermediate or high grade DCIS, which could be critical in determining the role of adjuvant RT
- Endocrine therapy has shown no benefit on local control in patients with ER+ PLCIS postexcision
Gross description
- Cut surface of breast tissue harboring PLCIS may have a faintly granular appearance when viewed with tangential light because affected lobules are sufficiently enlarged to be visible and microcalcifications are almost always present
Microscopic (histologic) description
- Pleomorphic LCIS is characterized by marked distention of the lobules filled with neoplastic cells
- Cells are medium to large with high N:C ratio, dyscohesive and evenly spaced
- Cytoplasm is moderate to abundant, dense eosinophilic or granular
- Intracytoplasmic vacuoles are present with or without mucin; may be large enough to produce signet ring cell forms
- Nuclei are ≥ 4x the size of a lymphocyte, eccentrically placed, often exhibit moderate to marked nuclear pleomorphism (> 2 - 3x variation in nuclear size) and distinct prominent nucleoli
- Chromatin is coarse and mitotic figures can be seen
- Binucleated and multinucleated cells are frequently seen (Am J Clin Pathol 2015;144:722)
- Frequently associated with central, comedo type necrosis and calcifications
- Clear cell change can be present similar to classic LCIS
- Myoid form of PLCIS is characterized by cells with dark eosinophilic to basophilic cytoplasm and deeply basophilic eccentric nuclei resembling myoblasts
- This appearance is seen typically in postmenopausal women, involves atrophic lobules and terminal ducts
- It is probably due to cytoplasmic condensation and loss of cohesion and shrinkage of cells
- Apocrine differentiation is seen sometimes, referred as apocrine PLCIS
- This change is characterized by abundant eosinophilic cytoplasm, cytoplasmic granules and prominent nucleoli
- Apocrine PLCIS appears to be a biologically distinct subtype which is GCDFP and AR positive
- It is mostly (~80%) negative for ER and PR, has HER2 gene amplification in 1/3 of cases and has elevated Ki67 (> 10%) (Am J Surg Pathol 2009;33:1683)
Microscopic (histologic) images
Contributed by Sucheta Srivastava, M.D. and Case #168
Characteristic microscopic features of PLCIS showing large, dyscohesive cells with abundant pink cytoplasm and intracytoplasmic vacuoles
PLCIS with prominent comedo necrosis and microcalcifications
ER staining (4x)
PR
E-cadherin staining (10x)
HER2
In situ and invasive disease
In situ and invasive disease
E-cadherin: in situ and invasive disease
Cytology description
- Cells have abundant cytoplasm compared with classic LCIS
- Nuclei are larger, more pleomorphic and frequently have nucleoli
- Nuclei may be bi- or multinucleated, lobulated, indented or eccentrically placed
- Cells can resemble those of DCIS and E-cadherin is helpful to make that distinction
- Intracytoplasmic mucin or signet ring cells can be present which can help to distinguish from DCIS
Positive stains
- Cytoplasmic p120 catenin (Arch Pathol Lab Med 2017 Jun 2 [Epub ahead of print], Int J Clin Exp Pathol 2014;7:2551)
- Nuclear ER, nuclear PR (95 - 100% in PLCIS; only positive in 15 - 20% cases in apocrine PLCIS)
- AR and GCDFP-15 (predominantly in apocrine PLCIS)
- Ki67 > 10%
- p53 ~25%
- HER2, mostly in apocrine PLCIS
Negative stains
- E-cadherin
- Most cases are negative for HER2 overexpression
Molecular / cytogenetics description
- Genetic signature of 1q gain and 16q loss combined with the lack of E-cadherin expression observed in PLCIS supports the lobular lineage for PLCIS along the multistep cancer progression pathway
- It is unclear whether PLCIS arises from classic LCIS and represents a genetically more advanced lesion or if PLCIS originates from a yet unidentified precursor lesion
- In one case with synchronous classic LCIS and apocrine PLCIS, both lesions shared 1q gain and 16q loss with additional chromosomal changes present in the apocrine PLCIS; this suggests evolution from the same precursor or through the same genetic pathway (Am J Surg Pathol 2009;33:1683)
- Some genetic abnormalities seen are HER2 amplification, cyclin D1 amplification, gain of 20q and loss of 17p and 13q
- At least some PLCIS are nonobligate precursors of invasive PLC analogous to high grade DCIS and invasive ductal carcinoma
- PLCIS and invasive PLC may develop through a molecular genetic pathway similar to classic lobular carcinoma, as these lesions harbor the hallmark molecular genetic features of lobular carcinoma (loss of 16q and gain of 1q) associated with lack of E-cadherin and β-catenin expression
- These lesions show additional molecular genetic changes more analogous to high grade DCIS including gains of c-myc (8q24) and HER2 (17q12), gains on 8p, 8q and 13q and losses on 1p, 8p, 12p, 14q, 18q, 19p and 19q
- PLCIS is characterized by amplification of HER2 and c-myc (8q24) oncogenes, which may account for (a) its higher grade and proliferation rate, (b) its more frequent progression to invasive carcinoma
- PLCIS may evolve through a molecular genetic pathway similar to that of classic LCIS but in addition also undergo additional genetic events (e.g. c-myc and HER2 amplification)
- PLCIS and invasive PLC are frequently associated with foci of classic lobular carcinoma and areas showing a morphological continuum between PLCIS and classic LCIS have also been described (J Pathol 2005;207:1)
Differential diagnosis
- High grade ductal carcinoma in situ: no intracytoplasmic vacuoles, mucin or signet ring cells; E-cadherin positive
- Apocrine intraductal carcinoma: predilection for lobular involvement; E-cadherin positive
Additional references
Board review style question #1
What is NOT a feature of PLCIS?
- Apocrine metaplasia
- Nuclei 4x the size of a lymphocyte
- Intracytoplasmic vacuoles
- Multinucleation
- Signet ring cells
Board review style answer #1
Board review style question #2
Which of the following is NOT true for PLCIS?
- Precursor for invasive carcinoma
- Positive E cadherin
- Positive ER and AR
- Abundant, dense eosinophilic cytoplasm
- Signet ring cells
Board review style answer #2
