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A REVIEW OF COLUMNAR CELL LESIONS IN FIBROCYSTIC CHANGE OF THE BREAST IN LAGOS
UNIVERSITY TEACHING HOSPITAL (LUTH); A 10 YEAR RETROSPECTIVE STUDY (JANUARY 2004 TO DECEMBER 2013)
BY
DR JIMOH, ABIMBOLA.M (MBBS)
A DISSERTATION TO BE SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE
AWARD OF FELLOWSHIP OF THE NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN
PATHOLOGY
2014.
2
CERTIFICATION BY SUPERVISORS
This is to certify that the study in this dissertation, A REVIEW OF COLUMNAR CELL
LESIONS IN FIBROCYSTIC CHANGES OF THE BREAST IN LAGOS UNIVERSITY
TEACHING HOSPITAL (LUTH); A 10 YEAR RETROSPECTIVE STUDY (JANUARY
2004 TO DECEMBER 2013), is the original work of Dr Jimoh Abimbola of the Department of Anatomic
and Molecular Pathology, Lagos University Teaching Hospital (LUTH), Idi-Araba, Lagos.
DR. A.O. DARAMOLA, MBBS, FMCPATH
Associate professor and consultant pathologist,
Department of Anatomic and Molecular Pathology LUTH, Idi-Araba, Lagos, Nigeria
SIGNATURE.................................................................................
Department of Anatomic and Molecular Pathology LUTH, Idi-Araba, Lagos, Nigeria
SIGNATURE.................................................................................
Professor and Consultant pathologist,
Lagos, Nigeria
CERTIFICATION BY HEAD OF DEPARTMENT
This is to certify that this research project, A REVIEW OF COLUMNAR CELL LESIONS IN FIBROCYSTIC CHANGES OF THE
BREAST IN THE LAGOS UNIVERSITY TEACHING HOSPITAL (LUTH); A 10 YEAR RETROSPECTIVE ( JANUARY 2004 TO
DECEMBER 2013), was conducted in the Department of Anatomic and Molecular Pathology, LUTH, Lagos.
Prof. F. B. Abdulkareem
Lagos University Teaching Hospital Idi-Araba, Lagos
Signature:__________________________________________
4
ACKNOWLEDGEMENT
To the Almighty God, my Father and my Friend I say thank you for everything.
My husband, Philip Iyayi, for all your support and love. My loving parents Akogun and Mrs B a b a t u n d e Jimoh,
without you I won’t be here today. I love you both.
To

To Professor Olusegun Ojo, for painstakingly and patiently teaching me the art of writing. I
appreciate all that you did for me. Thank you.











Acknowledgement
LIST OF TABLES
Table 6.1: Age Distribution of Cases of Fibrocystic Changes of the Breast
Table 6.2: Relationship between the Histopathologic Subtypes of Fibrocystic Changes of
the Breast and Age of the Patient
Table 6.3: Relationship between the Subtypes of FCC and Occurrence of CCLs Table 6.4:
Age Distribution of the Patient with FCC and CCLs
Table 6.5: Relationship Between Age Distribution of the patients and Pattern of CCLs
Found
8
LIST OF FIGURES
Figure 1: Photomicrographs of Columnar Cell Lesion with no atypia (a and b)
Figure 2: Photomicrograph of Columnar Cell Hyperplasia
Figure 3: Photomicrograph of Columnar Cell Change with atypia showing luminal
secretion and apical snouts
Figure 4: Photomicrograph of Columnar Cell Hyperplasia with atypia
Figure 5: Chart showing pattern and distribution of Columnar Cell Lesions in the study












UV - Ultraviolet
DAB - Diaminobenzidine
Objectives:
We set out to find out whether CCLs occur among Nigerian women and, if so, to estimate
their frequency of occurrence of CCLs, using fibrocystic change (FCC) as a surrogate lesion
so as offer us a peep into its real prevalence in the wider women population. We also set out
to determine the range of CCLs found using the recognized histologic criteria
Materials and methods:
11
INTRODUCTION
BACKGROUND
Columnar cell lesions have been generating the interest of pathologists in recent years as
they are a relatively new entity coming into clinical attention upon finding them in biopsy
specimen sent for the investigation of microcalcification on routine screening
mammography.
Screening mammography is not yet a widely practiced procedure in Nigeria therefore to be
able to study Columnar Cell Lesions we look at the cystic variant of Fibrocystic Changes
that appears to be the closest in morphologic features. These benign lesion come into clinical
attention as imaging abnormalities or as palpable lesions found on physical examination1
Fibrocystic Changes (FCC) of the breast fall into the non proliferative group having
morphologic patterns such as cysts lined by cuboidal epithelium often with apocrine
metaplasia, fibrosis and adenosis2. Similarly Columnar Cell Lesions (CCLs) have cysts
though lined by tall columnar epithelium with apocrine snouts making it possible for them to
have been previously lumped together however there is a need to separate them as some
studies have suggested that CCLs may have an increased risk for breast cancer progression3.
This entity has subsequently been described with a variety of names and several studies have
been carried out in this regard. Of note is the work done by Stuart.J.Schnitt who, along with
his team, have been involved in several studies4, 5,6,7,8 aimed at formulating better
standardized diagnostic criteria and classification for better projection of clinical
significance.
12
Schnitt and Vincent-Salomon were able to further characterize the morphologic features of
CCLs and classify them into four categories: Columnar Cell Change, Columnar Cell
Hyperplasia, Columnar Cell Change with atypia and Columnar Cell Hyperplasia with
atypia4. In 2003, the WHO introduced the term “Flat Epithelial Atypia” to describe the later
two categories. Flat epithelial atypia (FEA) is defined by the presence of a neoplastic
intraductal proliferation characterized by replacement of the native epithelial cells by a
single layer and up to 3-5 layers of mildly atypical cells.4 The Schnitt classification was
modified by Simpson PT et al in 2005 into six categories by addition of architectural atypia.9
Benign epithelial breast lesions have been re-classified and now include some new groups
such as Columnar Cell Lesions (CCLs), a heterogenous group which, in developed nations,
has been recognized for many years by pathologists and have been described under a variety
of names. In our environment however, the lesions in this group were hardly known among
pathologists until the last decade and have been lumped together with Fibrocystic Changes
of the breast as the cystically dilated glands seen in these lesions were often thought to be
microcysts of Fibrocystic Changes of the breast.
The major reason why this lesion is now coming to clinical significance is the fact that
CCLs are being picked up on routine mammographic screening of the breast carried out as
one of the cancer prevention strategies in the world over. As a result many silent but
important breast lesions are being detected. CCLs tend to be associated with
microcalcifications hence they are being detected more often now on histologic biopsy
specimen because of the increased use of mammographic screening. The study of these
13
lesions is done to have a better understanding of their biologic and prognostic significance,
in the Black women population.
A search of the available literature reveals no previous study of this nature has been
undertaken in Africa/blacks. The need for this study at this time is to determine the
frequency of Columnar Cell Lesions in black women, their age distribution and possible
implications.
Also this study hopes to draw clinical attention to Columnar Cell Lesions especially CCLs
associated with atypia because of the risk of malignancy associated with (FEA) which is
thought to represent a very early stage in the evolution of low-grade DCIS and invasive
carcinoma3
14
CHAPTER TWO
L I T E R A T U R E R E V I E W
2.1 COLUMNAR CELL LESIONS OF THE BREAST
Columnar Cell Lesions (CCLs) are defined as enlarged terminal duct lobular units (TDLU)
with dilated acini lined by tightly packed columnar epithelial cells with prominent apical
cytoplasmic snouts and intraluminal secretions10. They have been described under a variety
of names such as Blunt duct adenosis11, Columnar alteration with prominent apical snouts
and secretions (CAPSS)12, Clinging carcinoma13, Enlarged lobular units with columnar
alteration (ELUCA)14 etc. The use of these various names and terminologies have hindered
the pathologist’s understanding of their biological significance hence the evolution of the
classification and standard terminology scheme by Schnitt and Vincent- Salomon in 2003.4
The use of this scheme has facilitated the study of CCLs as a potential breast cancer risk
factor4.
The term ‘Blunt duct adenosis’ was introduced in 1945 by Foote and Stewart to describe a
condition affecting the terminal duct lobular unit (TDLU) characterized by hypertrophy
epithelial and myoepithelial layers with enlargement of lumina.15 ‘Columnar metaplasia’
was used by Bonser, Dossett and Jull in 1961to describe the same process. This term was
never taken into common usage but had the merit of recognizing that epithelial hypertrophy
was the main feature of the condition.16 Other terms used to describe this condition include
‘atypical cystic lobules’,17 ‘Columnar alteration of lobules’18, ‘Metaplasia cylindrique’19 and
Hyperplastic terminal grouping.
15
In the 1970s, Azzopardi coined the term ‘Clinging Carcinoma’ to describe a form of Ductal
Carcinoma in situ (DCIS) characterised neoplastic cells confined to the periphery of the
affected structures13. Clinging Carcinoma as described by Azzopardi bears close similarities
to Columnar Alterations with Prominent Apical Snouts and Secretions (CAPSS) reported by
Frasier et al. In 1998.12 The term CAPSS encompassed a spectrum of lesions affecting the
TDLU, observed in breast biopsies performed for the evaluation of microcalcifications.
Kasami et al. used the term ‘Enlarged Lobular Unit with Columnar Alteration’ (ELUCA) to
describe TDLU with columnar cell alteration.14 In 2003 S.J Schnitt and V. Salomon
described these lesions as a group as ‘Columnar Cell Lesions’ (CCLs) and further classified
them giving recognition to those with cytological atypia. The term ‘Flat Epithelial Atypia’
was introduced by the WHO to replace Columnar Cell Lesions with atypia in 2003 and these
are the present nomenclature till date.
Columnar Cell Lesions are usually discovered by a breast cancer screening mammogram
and in particular by the presence of microcalcifications9. About 75% of breast columnar cell
lesions will show microcalcifications and they usually have a round or pleomorphic and
heterogeneous appearance on mammography. Columnar Cell Lesions are typically
associated with calcifications of the calcium phosphate type and they become deposited
within the variably sized duct lumina of dilated terminal duct lobular units10.
In fact, in terms of all mammographic findings associated with breast calcifications,
Columnar Cell Lesions rank fifth, following Fibrocystic Changes of the breast,
Fibroadenoma, Ductal Carcinoma in situ (DCIS) and Sclerosing adenosis20. Fine needle
aspiration cytology would usually reveal clusters of epithelial cells which can be columnar
16
admixed with myoepithelial cells with or without apical snouts and calcification, 21 if there is
any concern at all, it will tend to be founded upon any 'atypical' appearance to the columnar
cells. FNA alone is not considered reliable for diagnosing or categorizing CCLs10.
Columnar cell lesions are commonly seen in premenopausal and perimenopausal women
usually between the ages of 44 to 513, 10, they occur bilaterally, are multifocal in most cases
and have not been recorded in men.
In the UK, studies have shown that Columnar Cell Lesions were reported in 42% of biopsies
specified for microcalcification radiographically.22Although no study has been done in
Nigeria on Columnar Cell Lesions, several studies have been carried out on benign breast
diseases with Fibroadenoma and Fibrocystic Changes topping the list in this category23.
2.2 Fibrocystic Changes of Breast
This applies to a miscellany of changes in the female breast that include predominantly of
cyst formation, adenosis and fibrosis. In the past, these lesions were called Fibrocystic
disease however since most of these changes have little clinical significance beyond the
need to distinguish them from cancer, the term Fibrocystic Changes is preferred.2
Overall, Fibrocystic Changes of the breast are the most common breast abnormality seen in
premenopausal women. These changes tend to arise during reproductive age and most likely
a consequence of cyclic breast changes that occur normally in the menstrual cycle. Estrogen
therapy and oral contraceptives do not seem to increase the incidence of these alterations,
oral contraceptives may, in fact, decrease the risk of the developing FCC.2
17
Fibrocystic changes can be subdivided into non- proliferative and proliferative patterns. The
non-proliferative changes are the most common types of Fibrocystic lesions, characterized
by an increased fibrous stroma associated with dilation of ducts and formation of variably
sized cysts while the proliferative changes comprise of epithelial hyperplasia and sclerosing
adenosis.
Epithelial hyperplasias are recognized by the presence of more than two cell layers. The
spectrum of the epithelial hyperplasia ranges from mild and orderly to atypical hyperplasias
with features that resemble in situ carcinoma.2 Sclerosing adenosis is significant because its
clinical and morphologic features may mimic those of carcinoma. They contain marked
intralobular fibrosis and proliferation of small ductules and acini. Studies have shown that
the non-proliferative pattern of FCC is more prevalent both in Black-African and other
races23,24
2.3 The relationship of Fibrocystic changes to Breast Cancer.
Although Fibrocystic Changes are benign, some features may confer an increased risk for
the development of cancer, risks ranging from minimal to significant increased risk of
development of breast cancer. Fibrosis, cystic changes, aprocrine metaplasia and mild
hyperplasia have minimal or no risk of development of breast cancer.2
Mild to florid hyperplasia without atypia, ductal papillomatosis and sclerosing adenosis have
a slightly increased risk (1.5 – 2 fold) of developing breast cancer. While on the other hand
are atypical hyperplasias whether ductal or lobular have a significantly increased risk (5
fold) of developing cancer of the breast.2
18
2.4 Fibrocystic change and Columnar cell lesions
Columnar Cell Lesions are a group of lesions suspected by several authors to lie within the
constellation of Fibrocystic Changes of the breast.25, 26 They share some similarities with the
certain patterns of Fibrocystic Changes such as presence of cysts and epithelial hyperplasia.
Columnar Cell Lesions of the breast share a resemblance with the cystic type of Fibrocystic
Changes of the breast hence its association with CCLs and this is what make FCC of the
breast an acceptable surrogate with which CCLs can be reasonably studied. The previous
terminologies used in describing CCLs such as ‘Blunt Duct Adenosis’, ‘Enlarged Lobular
Unit with Columnar Alterations’, ‘Columnar Alterations with Prominent Apical Snouts and
Secretions’ etc create a descriptive confusion between Fibrocystic Changes and Columnar
Cell Lesions of the breast.
2.5 Classification of Columnar Cell Lesions (CCLs)
CCLs are characterized by dilated TDLUs lined by columnar cells with prominent apical
snouts that are perpendicular to the basement membrane. The dilated acini may appear
rounded with a smooth outline giving it a rigid look, may be angulated or have a branching
configuration.10 There may or may not be an increase in cell layer, luminal secretions may
be present, calcifications are common and can be granular or psammomatous.27
The need for the classification of Columnar Cell Lesion arose as a result of the use of
various terminologies which hindered the Pathologist’s understanding of their biologic
significance hence the evolution of this classification. The use of this classification scheme
is to facilitate the study of CCLs as a potential breast cancer risk factor4
19
Columnar cell change (CCC) with no atypia
Columnar cell hyperplasia (CCH) with no atypia
Columnar cell change with atypia
Columnar cell hyperplasia with atypia.
And was modified by Simpson in 2005 as follows3:
Type 1 (columnar cell change, CCC): 1-2 cell layers, columnar cells have uniform
ovoid/elongated nuclei perpendicular to the basement membrane; without/
inconspicuous nucleoli; may have apical snouts but usually not prominent.
Type 2 (columnar cell hyperplasia, CCH): >2 stratified cell layers with variable
nuclear crowding and cellular micropapillations, but no complex architectural
patterns (i.e. no rigid bars, bridges or well-formed micropapillary structures);
cytology similar to type 1 but may have hobnail cells. Associated with intraluminal
calcification.
Type 3 (columnar cell hyperplasia with architectural atypia): >2 stratified cell layers
with complex architectural patterns (micropapillary, tufts, fronds, arcades, rigid
bridges or punched out spaces); type 2 cytology.
Type 4 (columnar cell hyperplasia with cytologic atypia): type 2 architecture; mild
to moderate cytologic atypia, may resemble tubular carcinoma.
Type 5 (columnar cell hyperplasia with cytologic and architectural atypia): type 3
architecture; type 4 cytology.
Type 6 (columnar cell change with cytologic atypia): 1-2 cell layers; type 4
cytology.
20
In the current WHO classification, CCLs with cytologic atypia are referred as Flat Epithelial
Atypia (FEA) in order to describe a presumably neoplastic intraductal alteration
characterized by replacement of the native epithelial cells by a single or 3-5 layers of mildly
atypical cells.3
2.6 COLUMNAR CELL CHANGE (CCC): is characterized by TDLUs with varying
degrees of dilatation and the normal epithelium is replaced by one or two layers of tall
columnar epithelial cells that have basally placed nuclei and apical cytoplasmic snouts. The
nuclei are arranged in a regular fashion perpendicular to the basement membrane, uniform
oval to elongated and have evenly dispersed chromatin without conspicuous nucleoli.10,27
The myoepithelial layer is retained or even prominent, mitotic figures are rare. The dilated
acini typically show undulating outline with irregular branching with or without associated
calcification10
Figure 1: Photomicrograph of Columnar cell change with no atypia (a) of a TDLU and
(b) showing apical snouts and flocculent secretion28
21
2.7 COLUMNAR CELL HYPERPLASIA (CCH): the acini are lined by more than
two cell layers. The nuclei are bland in appearance and are mostly perpendicularly arranged
to the basement membrane. There may be an appearance of hyperchromasia due to crowding
and overlapping. The architecturally hyperplastic columnar cells may form small mounds,
tufts or short micropapillations but they do not form bridges or true micropapillae. Apical
snouts more exaggerated than CCC are present along with luminal secretions and
calcifications which are sometimes psammomatous may be present27.
Figure 2: Photomicrograph of Columnar cell hyperplasia with no atypia showing
prominent apical snout and flocculent secretions.28
2.8 FLAT EPITHELIAL ATYPIA (FEA): a neoplastic proliferation of TDLUs
characterized by replacement of the normal epithelial cells by one to several layers of
monomorphic epithelial cells showing low grade cytologic atypia6. They have smooth
nuclear outlines lacking grooves and notches, chromatin pattern is fine and evenly dispersed
with one or two nucleoli seen. Mitotic activity is sparse or absent. Flat in this context is a
22
relative term simply denoting the absence of complex architectural patterns,7 such as well-
developed micropapillations, rigid cellular bridges, bars and arcades, or sieve-like
fenestrations, with evidence of cellular polarization within the micropapillations and bars or
around the fenestrations.
Figure 3: Photomicrograph of Columnar cell change showing atypical columnar cells
with apical snouts, flocculent secretions and calcifications.28
23
There is accumulation of cytoplasm at their poles giving rise to apical snouts. It is of note
that the cells may be cuboidal rather than columnar in shape18. They have dilated acini
which are often more regular in outline than the undulating pattern seen in non atypical
lesions i.e. internal borders of the dilated acini typically appear round and rigid and a
lymphocytic inflammatory infiltrate is commonly seen in the surrounding stroma10,27.
Figure 4: Photomicrograph of Columnar cell hyperplasia showing atypia28
24
The absence of architectural complexity and low grade cytologic atypia are two prerequisite
in making a diagnosis of FEA, by definition the architecture in FEA is flat, that is, it lacks
micropapillae, arches ,bridges ,cribriform spaces etc this is vital in separating this lesion
from ADH and low grade DCIS. Their cytological features may be alike but Atypical Ductal
Hyperplasia (ADH) and low grade DCIS have complex architecture. High grade cytological
atypia is not a feature of FEA, the presence of high grade cytological atypia even without
architectural atypia warrants a diagnosis of DCIS. Other names used to describe lesions
within the category of FEA are Atypical cystic duct29, Atypical cystic lobules30, Atypical
lobules type A31, Clinging Carcinoma13, Columnar Alteration with Prominent Apical Snouts
and Secretions with atypia5, Columnar Cell Change with atypia4, Columnar Cell Hyperplasia
with atypia4, Ductal Intraepithelial Neoplasia of the monomorphic type32, Hypersecretory
hyperplasia with atypia33 and Small ectactic ducts lined by atypical ductal cells with
apocrine snouts33.
Due to the fact that an element of subjectivity exists in such cytological assessments,
difficulties and controversies in assigning a diagnostic category to some borderline lesion
pose some practical problems but as pathologists gain more experience with these types of
lesions, hopefully a classification system based on more objective criteria will be adopted.
2.9 THE IMMUNOHISTOCHEMISTRY OF COLUMNAR CELL LESIONS
CCLs typically show positivity for CK8, 18 and 19 in keeping with their luminal epithelial
cell nature and show negativity for basal cytokeratin such as CK 5 and 6 therefore they are
not useful in differentiating CCLs with atypia and those without. CCLs show diffuse and
strong positivity for estrogen (ER) and progesterone (PR) and androgen receptor (AR). Bcl2
25
and cyclin D1 positivity, low proliferation indices with Ki-67 and reduced CD117
expression. CCLs are typically negative for HER2 and p5330, 35, 36. It is worth noting that
patients with ER negative CCLs were at increased risk of malignancy compared with those
whose lesion were ER positive, but as yet there are no confirmatory studies14
2.10 THE CLINICAL APPLICATION OF THE IMMUNOHISTOCHEMISTRY
OF CCLs
The Immunohistochemistry of CCLs is useful in differentiating them from some similar
lesions that share a form of morphological similarity or the other. ER-PR staining of usual
ductal hyperplasia appears heterogeneous and limited to about 10-15% of cells38 and express
basal markers such as CK5/6.
Studies have shown proliferative labelling index Ki67 of 0.3% in Columnar Cell Lesions
versus 13.7% in DCIS.
2.11 THE MOLECULAR BIOLOGY OF COLUMNAR CELL LESIONS
Loss of heterozygosity has been demonstrated in the majority of FEA with loci on 11q, 16q
and 3p being most commonly involved, these genetic alterations are similar to those
occurring in co-existent with DCIS or invasive carcinoma. Also there are recurrent losses on
16q, 17p, 17q, 10q, 9q and gains on 15q, 16p and 19p27.
The presence of identical genomic aberrations in CCLs matched with ADH and Low grade
DCIS provide strong circumstantial evidence to suggest that CCLs are part of a group of
inter-related lesions, the so called ‘low grade breast neoplasia family’ and they constitute the
first morphologically identifiable precursor of low grade breast cancer.32
26
Furthermore, molecular analysis have demonstrated that the majority of Columnar cell
lesions are clonal and neoplastic rather than hyperplastic.23 Interestingly the degree of
genetic changes found in Columnar cell lesions appears to mirror the degree of architectural
and cytological atypia found in different types of CCLS.9
Despite the overlapping morphology, phenotype and genetic aberrations found in Columnar
cell lesions and the fact that CCLs comprise a spectrum of lesions, from a clinical
standpoint, most authorities argue that the most important differentiation is between
Columnar cell lesions with atypia (FEA) and those without.
2.12 THE HISTOPATHOLOGICAL EVALUATION OF CCLs
CCLs are characterized by enlarged/dilated TDLUs lined by columnar cells with prominent
apical snouts that are perpendicular to the basement membrane. The dilated acini may
appear rounded with a smooth outline giving it a rigid look, may be angulated or have a
branching configuration.10 There may or may not be an increase in cell layer, luminal
secretions and calcifications are common.
A number of benign lesions are differentials of CCLs such as microcyst of Fibrocystic
Changes (FCC), Apocrine Cysts, Pseudolactational Change, Cystic Hypersecretory
Hyperplasia, Usual Epithelial Hyperplasia and differentiating FEA from Atypical Ductal
Hyperplasia and low grade DCIS10.
In the cystic variant of Fibrocystic Changes the cells lining the glands are flat or low
cuboidal cells in contrast to columnar cells10. In Apocrine cysts of the breast, though the
glands are lined by columnar cells, the cytoplasm is more granular also the nuclei are round
27
and open with a single prominent nucleolus unlike CCLs whose nuclei are ovoid. Also
hobnail cells, exaggerated apical snouts and flocculent intraluminal secretions are seen in
CCLs these features are absent in apocrine lesions. Unlike CCLs, apocrine cells
characteristically lack the expression of Bcl2 and ER. As for Pseudolactational change the
epithelial cells are cuboidal not columnar and the foamy appearance of the cytoplasm
producing lipid should point the pathologist in the right direction. With Cystic
hypersecretory hyperplasia the dilated ducts are lined by flat epithelium with a characteristic
abundance of luminal homogenous colloid-like material, there are no apical snouts and
apocrine metaplasia. In Usual hyperplasia (non atypical) the cells are ovoid with small
grooves or notches and slightly granular chromatin and small nucleoli. The cells of Usual
hyperplasia may show overlapping and a more disorderly arrangement compared to the
orderly arrangement of CCLs. To avoid over-diagnosis, some staining with cytokeratin 5
and 6 are helpful as they stain positively in usual hyperplasia.
CCLs with atypia (FEA) do not form complex architectural structure, if architectural atypia
is present as well as cytological atypia then a diagnosis of ADH or low grade DCIS is
appropriate.
It has been noted that CCLs sometimes coexist with other well defined lesions such as
lobular carcinoma, ADH, low grade DCIS and invasive carcinoma especially lobular
hyperplasia and lobular carcinoma in-situ but it is uncommon for various types of columnar
cell lesions to coexist in the same area. The “Rosen’s triad has been proposed for lesions
consisting of CCLs, Lobular carcinoma in situ and Tubular carcinoma.38,39
28
2.13 THE PROGNOSIS AND CLINICAL SIGNIFICANCE OF CCLs
CCLs of the breast encompass morphological spectrum which may coexist within a wide
range of lesions that may include in situ and invasive carcinoma.39 However the overall
biological significance of these lesions are not known.40
Eusebi et al discovered 25 cases (0.26%) of what was called low grade clinging carcinoma
of the flat type, but which appears morphologically equivalent to FEA, during an average
follow-up interval of 19 years, none of the 25 women with low grade clinging carcinoma of
the flat type developed invasive carcinoma and only one had a recurrence, which was
described as consisting of low grade clinging carcinoma of the flat type41, there are other
studies that also suggest that the risk of developing subsequent breast carcinoma in patients
with FEA is considerably low.8,42,43 At a more fundamental level, there is evidence that, in
general, there is progressive allelic damage in FEA through to DCIS.9,40 However because
of the scarcity of clinical follow up studies addressing the relationship of CCLs and
malignancy, long term follow-up studies are essential before definitive conclusions are
reached.
Finally the management for patients with CCLs is controversial. In a breast biopsy CCLs
with no atypia requires no further investigation or excisional biopsy however when FEA is
present a follow-up excisional biopsy is recommended because studies have shown that up
to 30% of formal excisional biopsies will demonstrate more significant pathology i.e. ADH,
DCIS, or invasive carcinoma and a thorough search must been carried out on the specimen.
The patient should be managed according to the most advanced lesion present. If FEA is the
most advanced lesion then it is probable that no further treatment is required but close
29
clinical monitoring is the current prevailing management10. It is worth mentioning at this
point that a constellation of Fine needle aspiration cytology (FNAC), core needle biopsy and
excisional biopsy are the standard approach in the investigation of CCLs43. However more
studies to better define the long term clinical and biologic significance of FEA are required.
There are specific groups of breast lesions that are difficult to diagnose using FNAC alone.
These include the non-palpable borderline lesions such as the florid epithelial hyperplasia,
columnar cell lesions including flat epithelial hyperplasia and ADH and low grade DCIS.
Although in general they have distinct cytological features, in actual daily practice, a
confident classification and differentiation of these entities is still unachievable. One needs
to put into proper clinical perspective that most of these lesions are non palpable and it is
difficult to ensure direct sampling at FNAC. Even with imaging guidance it may not be
possible to sample these lesions adequately by cytological means.44
Columnar Cell Lesions in breast core biopsies are typically sampled for histological
assessment of mammographic microcalcifications. These specimens should be examined at
multiple levels (at least three), if CCC or CCH only is found without atypia, the lesion
should be regarded as within the constellation of fibrocystic change and categorised as B2,
benign.45
Columnar Cell Lesions with atypia should be regarded as FEA and classified as B3, of
uncertain malignant potential.45 As for all such screen-detected lesions, multidisciplinary
discussion should be undertaken to correlate radiological, clinical and histopathological
findings.
30
The average age of occurrence of Columnar Cell Lesions is 45+ 2, most of these lesions
occurred in middle age though these findings are based on studies carried out on Caucasian
women. Since no study of this nature has been carried out on the black women race, no age
range is associated with these lesions. The predilection for any race or geographic
distribution has not been documented so far, this study hopes to shed light on issues as these.
31
RATIONALE FOR THE STUDY
Columnar Cell Lesions though have come to knowledge since the 1940s, is still evolving.
Several pathologists have carried out studies to determine the nature and clinical
significance of these lesions. However there is still a lot of grey areas and controversy in
the evaluation of its clinical significance.
Most of these studies have been carried out on the Caucasian female breast and,
geographically, in the western world. From an extensive review of literature done, no study
of this nature has been carried out on the African or African-American women population
or even in Africa.
Obviously, the study of Columnar cell lesions is in its early days and, in my own opinion, a
better understanding of this entity cannot be made until more studies are carried out among
all races and in more locales as to the nature and long term clinical significance of
Columnar cell lesions.
This study was carried out to establish whether Columnar Cell Lesions occur at all in
women of African descent, and if so, to determine their patterns of occurrence and
frequency. This study will hopefully ignite the desire in other researchers to evaluate the
lesion in terms of their long term clinical significance in black women and explore the
differences in the behaviour of the lesion in black and white women, if any.
32
At the present time, very little is known about the occurrence of CCLs in much of Africa
and Nigeria. In Nigeria, Screening mammography is not in widespread and consistent use.
This fact constitutes a serious impediment to the study of CCLs in this country.
However Columnar cell lesions of the breast share a resemblance with the cystic type of
Fibrocystic changes of the breast hence its association with CCLs and this makes FCC of
the breast an acceptable surrogate with which CCLs can be reasonably studied.
33
The aim and objectives of the study are as follows:
4.1 AIM
To investigate the occurrence and nature of CCLs in FCC in LUTH patients.
4.2 OBJECTIVES
1. To estimate the frequency of occurrence of CCLs in FCC to probably offer us a peep
into its real prevalence in the wider women population
2. To determine the range of CCLs found in those positive cases using the conventional
histologic criteria
3. To tabulate the relative proportions of these entities identified in 2 above
4. To evaluate these data in light of the current thinking on CCLs worldwide
5. Explore the implication of the findings in 2 and 3 above for the incidence of breast
cancer in Nigeria, if any.
34
5.1 THE STUDY DESIGN /INCLUSION CRITERIA
The study involved the analysis of tissue blocks and slides of the breast which received a
final histological diagnosis of Fibrocystic Changes of the breast at the Department of
Anatomic and Molecular Pathology of the Lagos University Teaching Hospital, between
January 2004 and December 2013.
The studies of Columnar Cell Lesions have been traditionally carried out among patients
who had undergone screening mammography. However, since this procedure is not in
widespread use in Nigeria, a surrogate lesion, FCC was used.
The decision to select only FCC of the breast stemmed from the fact that Columnar Cell
Lesions have features that can be seen in the cystic variant of Fibrocystic Changes of the
breast hence the justification for them to have been previously lumped together.
5.2 THE STUDY POPULATION
Selection Criteria: All consecutive cases of FCC of the breast within January 2004 and
December 2014 were selected.
The materials that were used for this study were duplicate copies of histopathological
reports that were issued within this period, tissue blocks and corresponding archival slides.
40 cases were excluded from this study because their tissue blocks and corresponding slides
were missing.
5.3 THE METHODOLOGY
Bio data and hospital information such as patient’s age, hospital numbers laboratory
numbers and clinical details were extracted from the departmental register. Blocks and
corresponding archival routine haematoxylin and eosin (H&E) stained slides of all the cases
diagnosed within the ten year study period as fibrocystic changes of the breast within the
period in question were retrieved. The archival slides were reviewed and re-classified based
on the current WHO classification5 as: Columnar cell change, Columnar cell hyperplasia
and Flat epithelial atypia. Only those that met the criteria for CCLs were so re-classified.
The diagnostic criteria are as follows:
1. Presence of 1-2 layers columnar epithelial cells lining the glands with no atypia were
called columnar cell change28.
2. The presence of greater than 2 layers of columnar epithelial cells lining the glands
with no atypia were called columnar cell hyperplasia28.
3. The presence of even a layer of columnar epithelial cell with atypia lining the glands
but no architectural atypia was called flat epithelial cells28.
5.4 IMMUNOHISTOCHEMICAL ANALYSIS
Immunohistochemical studies for ER antibodies were carried out on fresh sections that were
prepared from tissue blocks of the cases of CCLs. The decision to stain the cases with ER
immunostain arose from previously documented studies35,45 which showed that Columnar
cell lesions demonstrated diffuse and strong positivity for the Estrogen Receptor.
36
5.5 DATA ANALYSIS
The data generated included the range and types of Columnar Cell Lesions, age distribution
and the range of Fibrocystic Changes. These non-parametric data were analysed manually
using tables and simple arithmetical analysis such as percentages and proportions.
5.6 ETHICAL CONSIDERATION
Approval for the study was obtained from the Research & Ethical committee of Lagos
University Teaching Hospital (LUTH). The permission of the Head of the Department of
Anatomic and Molecular Pathology was also sought for the use of the laboratory and other
archival materials where required.
RESULTS
6.1 A total of 559 consecutive cases of Fibrocystic Changes of the breast were obtained
during the study period and analysed for the purpose of this study.
The frequency of Fibrocystic Changes of the breast, the components of FCC and pattern of
CCLs were correlated.
Table 6.1: Showing the Age Distribution of the Cases of Fibrocystic Changes of the
Breast
11-19 Years 55 10%
20-29 Years 179 32%
30-39 Years 156 28%
40-49 Years 121 21.5%
50-59 Years 30 5.3%
60-69 Years 18 3.2%
Total 559 100%
Mean Age=36±12, Min Age=16, Max Age=63, Std Dev=12.104
Table 6.1 shows the age range of cases analysed was 16 years to 63 years, mean age was
36years (SD = 12.1). One hundred and seventy nine cases of Fibrocystic Changes of the
breast occurred in the 3rd decade making up 32% of all the cases. One hundred and fifty six
cases (28%) occurred in the 4th decade while 121 cases (21.5%) occurred in the 5th decade
while 55 (10%) cases occurred in the 2nd decade. There were 30 cases (5.3%) in the 6th
decade and 18 cases (3.2%) seen in the 7th decade.
38
Table 6.2: Showing the Relationship Between the Histopathologic subtypes of
Fibrocystic Change and Age of the patients.
AGE
CYST
FORMATION
STROMAL
FIBROSIS
ADENOSIS
EPIPHELIAL
PROLIFERATION
11-19 44 7.8% 42 7.5% 13 2.3% 5 0.9%
20-29 163 29.2% 160 28.6% 53 9.5% 18 3.2%
30-39 149 26.6% 149 26.6% 87 15.5% 10 1.8%
40-49 120 21.5% 121 21.6% 63 11.3% 7 1.3%
50-59 25 4.5% 30 5.4% 5 0.9% 4 0.72%
60-69 18 3.2% 18 3.2% 10 1.8% 2 0.36%
TOTAL 519 92.8% 520 93% 231 41.3% 46 8.2%
Table 6.2 show the different components of Fibrocystic Changes of the breast comprising of
Cyst formation, fibrosis, Adenosis and Epithelial proliferation. Stromal fibrosis and cyst
formation occurred in 520 and 519 cases respectively of all 559 cases while adenosis and
epithelial proliferation occurred in 231 and 46 cases respectively. The largest number of
cases occurred in the 3rd decade for each component and the least occurred in the 7th decade.
39
Table 6.3: Showing the Relationship between the Subtypes of FCC and Occurrence of
CCLs
11-19 44 3 42 0 13 1 5 0
20-29 163 4 160 0 53 1 18 1
30-39 149 4 149 0 87 1 10 2
40-49 120 6 121 1 63 0 7 1
50-59 25 3 30 1 5 0 4 1
60-69 18 0 18 0 10 0 2 0
TOTAL 519 20 520 2 231 3 46 5
Table 6.3 depicts the relationship between the variants of FCC and the occurrence of CCLs
in the various age groups. The largest numbers of the variants of FCC occurred in the 3rd
decade however this does not correlate with the largest number of CCLs which occurred in
the 5th decade. Most of the CCLs occurred in the cystic subtypes of FCC with a total of 20
cases through all the age groups, epithelial proliferation variant had 5 cases in total, 2 cases
in the fibrotic variant and 3 cases in the adenotic variant.
40
Figure 5: Chart showing the patterns of Columnar Cell Lesions in the study
Figure 5 show the histopathological pattern in the 30 cases obtained. The most common
histopathological pattern is pure Columnar Cell change with no atypia CCC (66.7%) in 20 of
the 30, Columnar Cell Hyperplasia CCH in 5 cases (16.7%) and CCC and CCH coexisting
in 5 cases (16.7%). No case of Flat Epithelial Atypia (FEA) was found.
41
Table 6.4: Age distribution of the Patients with FCC and CCLs
Age Range FCC CCLs
11-19 55 9.8% 4 13.3%
20-29 179 32% 6 20%
30-39 156 28% 7 23.3%
40-49 121 21.6% 8 26.7%
50-59 30 5.4% 5 16.7%
60-69 18 3.2% 0 0%
TOTAL 559 100% 30 100%
Table 6.4 shows the occurrence of Columnar Cell lesions in Fibrocystic Changes of the
breast in each age group. Eight cases of CCLs occurred in 121 cases of FCC in the 5th
decade, 7 cases of CCLs in 156 cases of FCC in the 4th decade and 6 cases of CCLs in 179
cases of FCC in the 3rd decade. There were 5 cases of CCLs in 30 cases of FCC in the 6th
decade, 4 cases of CCLs in 55 cases of FCC in the 2nd decade and no cases of CCLs in 18
cases of FCC in the 7th decade.
42
Table 6.5: Relationship between Age Distribution of the Patients and Pattern of CCLs
found
PATTERN
20-29 Years 5 1 0
30-39 Years 6 0 1
40-49 Years 6 1 1
50-59 Years 1 3 1
60-69 Years 0 0 0
Total 20 5 5
66.7% 16.7% 16.7%
Table 6.5 show the range of patterns of Columnar Cell Lesion that occurring in different age
groups. Six cases of Columnar Cell Change occurred in the 4th and 5th decade while 5 cases
occurred in the 3rd decade. Two cases of CCC were seen in the 2nd decade while only one
case was seen in the 6th decade.
The table shows cases of mixed CCC and CCH pattern, 3 cases of such occurred in the 6th
decade while 1 cases occurred both in the 3rd and 5th decade. The 2nd, 4th and 7th decade had
no cases of CCLs.
Columnar Cell Hyperplasia was seen in 2 cases within the 2nd decade while 1 case was seen
in the 4th, 5th and 6th decade. No cases of CCH were seen in the 3rd and 7th decade.
43
Table 6.6: Showing the Frequency of Each Types of CCLs found
Age Frequency CCC CCC & CCH CCH
11-19 4 2 0 2
20-29 6 5 1 0
30-39 7 6 0 1
40-49 8 6 1 1
50-59 5 1 3 1
60-69 0 0 0 0
TOTAL 30 20 5 5
Table 6.6 shows the frequency of the range of CCLs within the different age groups. Of the
8 cases of CCLs seen in the 5th decade 6 were CCC, 1 mixed CCC and CCH and 1 CCH,
there were 7 cases in the 4th decade of which 6 were CCC, 0 cases for the mixed pattern and
1 case of CCH.
Six cases of CCLs occurred in the 3rd decade, of these, 5 were CCC, 1 mixed pattern and
none was seen for the CCH pattern. In the 6th decade there were 5 cases, 1 case of CCC, 3
mixed pattern and 1 case of CCH and in the 2nd decade there were a total of 4 cases of CCLs
seen, 2 cases were CCC and CCH each. There was no case of CCLs in the 7th decade.
44
Figure 6: Photomicrograph of Columnar Cell Change with no atypia (H&E x 100)
45
Figure 7: Photomicrograph of Columnar Cell Change with no atypia (H&E x 100)
46
Figure 8: Photomicrograph of Columnar Cell Change with micro-calcifications (H&E
x100)
47
Figure 9: Photomicrograph of Columnar Cell Change and Columnar Cell Hyperplasia
with no atypia containing flocculent secretions (H&E x100)
48
Figure 10: Photomicrograph of Columnar Cell Hyperplasia with no atypia (double
arrow) and apocrine metaplasia (single arrow) (H&E x 100)
49
Figure 11: Photomicrograph of Columnar Cell Change with microcalcifications and
flocculent secretions (H&E x100)
50
Figure 12: Photomicrograph of ER positive immunostain Columnar Cell Change with
no atypia (x 100)
DISCUSSION
In this study, we looked into the occurrence of Columnar Cell Lesions and determined the
most predominant pattern among Nigerian women as most of the studies carried out so far
have been among Caucasians. The study was carried out using Fibrocystic Changes of the
breast as a surrogate lesion because mammography is not yet widely done in Nigeria and
CCLs bears some similarities with certain subtypes of FCC.
7.1 FIBROCYSTIC CHANGES OF THE BREAST
Fibrocystic Changes (FCC) of the breast, comprising of a constellation of changes of cyst
formation, fibrosis adenosis and epithelial proliferation, are a rather common benign
disorder that affect women within their reproductive years the world over. Some variants of
FCC, principally the epithelial proliferation variants, have been associated with an increased
risk of subsequent malignant change.2,10 However, it is emerging in recent literature that
Columnar Cell Lesions (CCLs), while not clearly belonging to this previously identified
FCC categories, may bear some risk of malignant change also.3,4,5,7,8,9 CCLs have not been
studied among black women before now because their existence has not been reported
among them. In this study we sought to identify CCLs among FCC cases as a starting point
for the study of CCLs among black subjects.
52
7.1.1 Occurrence
The total number of cases of FCC found by us within the 10-year study period was 559
cases, when compared with a study conducted in Ile-Ife on benign breast diseases23 which
includes Fibrocystic Changes of the breast was found to be significantly higher than that of
Ile-Ife which had 60 cases of Fibrocystic Changes for the same period of time.
There is a significant difference in the number of cases seen between the two studies, this
can be explained by the fact that this study was conducted in an urban area and it would be
expected that there will be more patients with a wider variety of lesions which FCC was one
of them.
In our series, the highest number of cases was in the 3rd decade where 179 (32%) cases
occurred. This finding shows similarity with other studies46, 47, 23 carried out in Ibadan, Kano
and Ile-Ife that FCC had a peak occurrence in the third decade and showed a relatively high
prevalence till the 5th decade before it declined.48
Most studies in the literature on FCC and other breast lesions both benign and malignant
were done among Caucasian subjects. The documented age range of the patients with
fibrocystic changes of the breast among Caucasians is between 20-50 years10 which is the
same as that of this study and similar studies conducted in Nigeria as well as this one.
7.1.2 The Effects of Age on FCC
Fibrocystic Changes of the breast as mentioned earlier had the highest incidence in the 3rd
decade of life followed by the 4th decade till the 5th decade. These periods in a woman’s life
marks the peak of the reproductive period. Many studies have suggested that FCC occurs in
53
the reproductive periods of a woman’s life23, 46, 47, 48 because of the presence of circulating
hormones. Therefore, expectedly, there is a decline of FCC in post menopausal women
which usually occurs at the end of the 5th decade to the 6th decade. The age range of the
patients with FCC in this study is 16-63 which is also in consonance with the study done in
Ile-Ife whose recorded age range for Fibrocystic Changes of the breast was 16-60.23
7.1.3 Clinical importance of FCC
Fibrocystic changes of the breast are generally regarded as harmless however certain
variants are associated with an increased risk of breast cancer progression hence the need for
follow-up when these changes are found.
In this study, the majority of the cases presented with cysts and fibrosis with fewer cases of
adenosis and epithelial proliferation, although there were overlaps of the variants in many
instances. This finding is in agreement with the study on benign breast diseases conducted in
Ile-Ife23 that found more variants of cyst formation and stromal fibrosis over sclerosing
adenosis and epithelial proliferation.
In current literature, cystic and fibrotic variants of FCC have been classified under the non-
proliferative pattern and have mininimal or no clinical implication. The Proliferative group
of FCC comprising of sclerosing adenosis and epithelial proliferation have a 1.5-2 fold
increased chances of progression to breast cancer.2
A study done in Yonsei, South Korea24 had majority of the women 92.5% with non-
proliferative pattern of FCC this is in consonance with the findings in this study as well as
similar studies done elsewhere in Nigeria.23,46,47,48 The clinical import of this for our
54
patients, in my opinion, is that there is no or minimal risk of progression of FCC to breast
cancer as the majority of cases were in the non-proliferative group.
7.2 Columnar Cell Lesions
7.2.1 Relationship between Columnar Cell Lesions and Fibrocystic Change of the
Breast
Thirty cases of Columnar Cell Lesions were found in 559 cases of Fibrocystic Changes of
the Breast in this study. Extensive literature search reveal no previous study of this nature
that has been carried out. This study is unique because the study population was pre-defined
by the occurrence of FCC in the subjects in the first place. Traditionally, CCLs, as an entity,
arose out of studies of biopsies that are done after screening mammography reveal calcific
anomalies in the subjects. Since screening mammography is novel in Nigeria, we were
unable to do the traditional-type study. Our findings can therefore only be seen as arising
from an initial, pioneering foray into this field locally in Nigeria.
The putative relationship between Columnar Cell Lesions and Fibrocystic Changes of the
breast provide the legitimizing plank for this study. The microcyst variants of FCC and
CCLs in my own opinion share a similarity that makes it possible for CCLs to have been
hidden in the category of the cystic variant of FCC in the past. However it is obvious at this
point that they are not the same but are different entities that carry different degrees of
association to breast cancer as CCLs only share a similarity with the cystic variant which is
only a subset of FCC. This relationship is depicted in table 6.3 where 30 cases of CCLs were
found in 559 cases of FCC, the majority of CCLs were found within the cystic variant this
further buttresses the opinion that the cystic variant of FCC and CCLs share some
similarities.
55
Fibrocystic changes of the breast contain cysts, stromal fibrosis, adenosis and epithelial
proliferation. The latter two variants confer a 1.5-2 fold chance of progression to the breast.
On the other hand, CCLs are cystically dilated TDLU lined by columnar cells with or
without epithelial hyperplasia and lack of architectural complexity. The presence of
cytological atypia in CCLs makes it FEA5,28 which is a precursor of breast cancer.
7.2.2 The Age Occurrence of Columnar Cell Lesions of the Breast
In this study, we have been able to show that Columnar Cell Lesions exists among Nigerian
women. It is perhaps most common during the 5th decade, this agrees with studies conducted
on Caucasian women that the highest prevalence of CCLs is between ages of 44-51.3, 4, 8, 10
On reviewing the existing body of literature on the subject, it appears that the jury is still out
on why Columnar Cell Lesions occur majorly in middle age or its association with this age
group.
7.2.3 The Histopathological types of CCLs
In this study, we found that 67% of Columnar Cell Lesions were Columnar Cell Change
with no atypia which came to 20 cases of the 30 cases of CCLs. Literature so far has not
documented a predominant type of Columnar Cell Lesion. This is probably because it is
believed that only the atypical types are important. There were 5 cases of Columnar Cell
Hyperplasia and an overlap between CCC and CCH for the remaining 5 cases.
In this study, we found no case of Flat Epithelial Atypia (FEA). This could be due to the
restriction on the number of cases identifiable by us that is imposed by our using FCC as the
surrogate defining lesion of our study population. It is possible that in the future, larger
56
studies on CCLs would identify some cases of FEA. We are therefore unable to make any
comment here on its clinical significance as being a putative precursor of low grade DCIS
among Nigerians.
7.2.4 Clinical and Biological importance of CCLs
Columnar Cell Lesions are believed to be possible precursors of breast cancer because they
share immunohistochemal and molecular properties with atypical Ductal hyperplasia (ADH)
and DCIS.9, 23, 26, 31 however the overall biological significance is unknown.40 there are some
school of thought that says it is a marker of coexistence of breast cancer as opposed to being
a precursor to it.37, 38 Due to the fact that no FEA was identified in this study no deductive
comments can be made on its clinical significance in Nigerian women.
7.2.5 Screening tools for CCLs
Columnar Cell Lesions have been generating interest among pathologists in the recent years
as they come into clinical attention because of their frequent observation in biopsy specimen
taken as a follow-up of screening mammography. As one of the breast cancer screening tools,
screening mammography has brought CCLs into the spotlight in many countries where this
is routinely done.
There is obviously a need for routine mammographic screening to be instituted in Nigeria as
a tool in early detection of breast cancer and probably of its putative precursor lesions such
as FEA, ADH etc. This is because early detection would bring about significant reduction in
breast cancer morbidity and mortality generally.
57
7.3 Conclusions
At the end of this study, we come to the conclusion that Columnar Cell Lesions occur in
Nigeria and, by extension, the black women population. We have also shown that Columnar
Cell lesions are related to Fibrocystic Changes of the breast. The prevalence of CCLs in
FCC is (30/559) 5.37%. Perhaps there could be more Columnar Cell Lesions hidden within
other categories of benign breast diseases, borderline breast lesions and malignant breast
lesions but these other lesions were not explored for the purpose of this study because of the
limitation imposed by the nature of the sample.
A major negative finding in this study is that no case of FEA was found, this could be also
due to the defining criteria of the study population that has put a restriction on the variety
and extent of the sample. Obviously, larger studies need to be done in order to extend the
applicability of our conclusions.
We recommend that Pathologists should become more aware of Columnar Cell Lesions,
because certain variants, particularly FEA, have been identified as precursor lesions to low
grade DCIS.
CHAPTER EIGHT
FURTHER WORK
This study was conducted to gain insight into the occurrence and possible biologic and
clinical significance of Columnar Cell Lesions in the Black women population. CCLs have
been identified and studied within the context of screening mammography, a procedure that
is still novel in Nigeria.
Thus, in this study, we have had to improvise by studying CCLs among a cohort of cases of
Fibrocystic Changes of the breast. Understandably, this has imposed some limitation on
inferences that could be made from our findings.
In future studies, preferably at a time when screening mammography in Nigeria becomes the
norm, research work should be conducted on a larger population of women. It is
recommended that such studies should include a follow-up plan in order to be able to
determine the its clinical significance of CCLs in the patients thus studied.
59
LIMITATIONS OF THE STUDY
The interest in CCLs has been ignited by the finding of a strong association between them
and microcalcifications detected on screening mammography for breast cancer where this is
a routine procedure and core needle biopsies were taken for evaluation of non palpable
lesions with microcalcification for presence of atypia
This has led to the desire to study CCLs in our environment however this study was not
based on mammographic studies. Rather Fibrocystic Changes of the breast (FCC) was
employed as a surrogate lesion and the basic selection criteria for the sample population
because of the similarities it shares with the cystic variant of FCC making it an acceptable
surrogate in which this study can be reasonably carried out. Thus the Fibrocystic Changes of
the breast bias obviously was a major confounding variable limiting the number of cases and
skewing its distribution among women in Nigeria.
The findings can therefore not be representative and the deductions not universally
applicable. However, this study should be seen as a pioneer one, in this field, beckoning for
larger ones when mammography becomes a routine screening proceedure in Nigeria.
60
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Take sections to distilled water
Antigen retrieval should be done using HIER in citrate buffer and allow to cool for
20minutes.
Rinse in 2 changes of distilled water
Rinse with the wash buffer (Posphate buffer)
Block using hyprogen peroxide block for 10minutes depending on manufacturer’s
instruction.
Rinse in two changes of wash buffer
Add a UV block for 5minutes (some manufacturers skip this step)
Flip off the UV block (do not rinse)
Add the primary antibody (ER, PR, and CK 8, 18 or 19) for about 30 min or 1 hour
depending on manufacturer
Rinse in 2 changes of wash buffer
Add an antibody enhancer (varies depending on the kit being used)
Rinse in 2 changes of wash buffer
Add the secondary antibody
Add Dab substrate and chromogen mixture for 10 minutes
Rinse in distilled water
Counter-stain in Mayer’s haemalum for 1or 2 minutes