Get Permission Rajkumari and Pallipady: Overdiagnosis of lobular carcinoma of breast- A review of histomorphological features and immunohistochemistry: A case series


Introduction

Invasive lobular carcinoma (ILC) accounts for 5%–15% of all invasive breast cancers (BCs) and is the second most common type of BC behind invasive ductal carcinoma (IDC) of no special type.1, 2 ILC of the breast is characterized morphologically by small, non-cohesive cells that infiltrate the stroma in a single-file pattern(Indian file pattern).3 ILC tumours display features associated with a good prognosis, being low grade, oestrogen receptor positive and is mainly associated with the complete loss of E-cadherin (E-cad) expression.4, 5

Our aim through this case series is to report our experience and discuss the diagnostic pitfall in histopathological evaluation alone.

Case Presentation

We report a case series of 10 modified radical mastectomy specimens which were diagnosed as invasive lobular breast carcinoma for a period of 1 year: January 2021 to January 2022. The mean age of our patients was 55.9 years old (35–72). All the patients included were female. The classic presentation was a breast lump found in all the cases (100%). The lesions were in the right breast in four cases (40%) and the left one in six cases (60%). The average size of the tumours was 4.5 cm (1.4-9 cm). Clinically, lesions suspicious of breast carcinoma were present in all the 10 patients (100%). All the 10 patients had undergone modified radical mastectomy and the specimens were sent to our laboratory for histopathological diagnosis. (Table 1)

Table 1

The patient characteristics and the findings

Patients

Age (in years)

Chief complaints

Laterality

Tumor size(in cms)

TNM classification

Histological diagnosis

Surgery

1

35

Breast lump

Right

5*4.2*1

pT3N0MX

ILC

MRM

2

57

Breast lump

Right

5*4*3.5

pT3N0MX

ILC

MRM

3

61

Breast lump

Right

1.4*1*0.9

pT1CN1aMX

ILC

MRM

4

67

Breast lump

Left

1.4*1*0.7

pT4bN2aMX

ILC

MRM

5

40

Breast lump

Left

5*5*4

pT3N2aMX

ILC

MRM

6

44

Breast lump

Left

6*5.5*3.5

pT4N3aMX

ILC

MRM

7

72

Breast lump

Left

4*3.6*2.4

pT3N1aMX

ILC

MRM

8

48

Breast lump

Right

9*4.5*1.6

pT3N3aMX

ILC

MRM

9

67

Breast lump

Left

3*2.9*2.7

pT2N0MX

ILC

MRM

10

68

Breast lump

Left

6*6*4.2

pT3N1aMX

ILC

MRM

The 10 cases of breast cancer were first diagnosed as invasive lobular carcinoma of the breast on histopathological evaluation alone (Table 2) with 10 cases (100%) showing Indian file pattern or linear file pattern (Figure 1, Figure 2) followed by targetoid pattern in 2 cases (20%). 6 cases (60%) were given a histological staging of T3 followed by T4 staging in 2 cases (20%). 3 cases (30%) had N1 nodal status with N2 and N3 nodal status seen in 2 cases (20%) each.(Table 3).

Final immunohistochemical analysis showed 6(60%) cases with estrogen and progesterone receptor positivity. 9(90%) out of those 10 cases were Her2/Neu negative. E-cadherin analysis was done in all the 10 cases which showed positivity in 7(70%) out of 10(100%) cases. (Figure 3)(Table 5). Review after final immunohistochemical analysis yielded 7/10 cases to be IDC.

Table 2

Histological pattern of invasive lobular carcinoma as reported

Histological Pattern

No. of cases

Indian file pattern

10

Targetoid pattern

2

Solid pattern

0

Tubulo-alveolar pattern

1

Pleomorphic pattern

1

Table 3

Histological stage at the time of diagnosis

Characteristics

No. of patients (%)

Median age at diagnosis:

55.9 Years

Laterality

Right

4(40%)

Left

6(60%)

Bilateral

0

Histology

T stage

T1

1(10%)

T2

1(10%)

T3

6(60%)

T4

2(20%)

NODAL stage

N0

3(30%)

N1

3(30%)

N2

2(20%)

N3

2(20%)

Metastasis

MX

10

Table 4

Immunohistochemical diagnosis

Case

ER Status

PR Status

Her2/Neu

E-Cadherin

Final Diagnosis

1

+

+

-

+

IDC

2

+

+

-

-

ILC

3

+

+

-

-

ILC

4

+

+

-

-

ILC

5

+

+

-

+

IDC

6

-

-

-

+

IDC

7

+

+

-

+

IDC

8

-

-

-

+

IDC

9

-

-

+

+

IDC

10

-

-

+

+

IDC

Table 5

Distribution of IHC findings

IHC Markers

No. of patients (%)

Estrogen receptor

Positive

6(60%)

Negative

4(40%)

Progesterone receptor

Positive

6(60%)

Negative

4(40%)

Her2/neu

Positive

1(10%)

Negative

9(90%)

E-Cadherin

Positive

7(70%)

Negative

3(30%)

Figure 1

H and E section (10x-low power)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/8e48ca19-7b31-427f-bead-fcce843bffa0/image/6c47d9da-5206-409f-ad8f-13af72a0f3ae-uimage.png

Figure 2

H and E section (40x-high power)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/8e48ca19-7b31-427f-bead-fcce843bffa0/image/60585364-ea37-4927-a465-6122e4221172-uimage.png

Figure 3

E-cadherin IHC: Positive in tumor cells

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/8e48ca19-7b31-427f-bead-fcce843bffa0/image/97d47c59-303e-4e8f-9248-34587cd8d6ea-uimage.png

Discussion

In the first study of lobular carcinoma of breast done by Foote and Stewart in 1941, they described lobular carcinoma where the tumor shows linear infiltration in surrounding stroma in rows or Indian file pattern or targetoid appearance around the ducts as seen in our study (Figure 1). But the assignment of a growth pattern to either ductal or lobular or mixed type(NST/ILC) remains to some extent subjective as found in a study done by Matthias Christgen et al. ILC and its variants i.e Solid, alveolar, tubulo-lobular and the pleomorphic variants add difficulty in distinguishing the IDC of no special type, with the cord like or the trabecular patterns. Hence, High grade invasive breast carcinoma-NST should be kept in mind as differential diagnosis of invasive lobular carcinoma and its variants.6 As in a study done by R Singhai et al., diagnostic difficulties had occurred in some cases, because IDC showed a dispersed growth pattern, which included infiltration around the benign ducts in a targetoid manner, which is similar to that in ILC. The loss of E-Cadherin can be reliably checked, for distinguishing the ILC variants from IDC.7 A negative E-cadherin stain acts as a sensitive and specific biomarker to confirm the diagnosis of invasive lobular carcinoma.8

Authors’ Contribution

Data collection, review of the literature and drafted the manuscript. All authors have read and approved the final manuscript.

Source of Funding

No funding was received.

Conflict of Interests

The authors declare no conflict of interests.

References

1 

A Gogia V Raina SV Deo NK Shukla S Mathur BK Mohanti Clinico-pathological characteristics and treatment outcome in invasive lobular carcinoma of the breast: An Indian experienceIndian J Cancer201855434447

2 

M Cristofanilli A Gonzalez-Angulo N Sneige SW Kau K Broglio RL Theriault Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomesJ Clin Oncol2005231418

3 

D Pandiar T Smitha Single file" pattern in histopathologyJ Oral Maxillofac Pathol20202422045

4 

E Rakha I Ellis Lobular breast carcinoma and its variantsSemin Diagn Pathol2010274961

6 

SV Jagtap A Beniwal PG Chougule HP Shah SS Jagtap Invasive Lobular Carcinoma of Breast Histopathological Subtypes: Clinicopathological StudyJ Int Med Res20164963000605211017039

7 

K Pai P Baliga BL Shrestha E-cadherin expression: a diagnostic utility for differentiating breast carcinomas with ductal and lobular morphologiesJ Clin Diagn Res2013758404

8 

M Christgen D Steinemann E Kühnle F Länger O Gluz N Harbeck Lobular breast cancer: Clinical, molecular and morphological characteristicsPathol Res Pract2016212758397



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Article History

Received : 29-11-2022

Accepted : 30-01-2023


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Article DOI

https://doi.org/10.18231/j.ijpo.2023.011


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