Anoverviewofhairfollicle tumours.pdf

1. An overview of hair follicle
tumours
Zlatko Maru
si
c
Eduardo Calonje
Abstract
Tumours derived from/differentiating towards the hair follicle are rela-
tively rare and the nomenclature is somewhat confusing. A seemingly
difficult task of classifying and stratifying various follicular tumours can
be made easier by grouping various follicular tumours according to
lines of differentiation pertaining to the specific anatomical compart-
ments within the hair follicle. This review paper aims to improve the un-
derstanding of follicular tumours and provide several key points in
order to facilitate their diagnosis.
Keywords follicular; hair germ; infundibular; isthmic; matrix;
trichilemmal
Introduction
Tumours derived from or differentiating towards the hair follicle
represent a subgroup of cutaneous adnexal tumours. Even
though basal cell carcinoma (BCC) is included in follicular
tumour sections of certain textbooks due to features shared by
BCC germ cells and follicular matrix cells, it is classified as ker-
atinocytic and not appendageal in the 2018 WHO classification.1
Therefore, it is safe to say that follicular tumours are relatively
rare, like other adnexal tumours. Follicular tumours display a
wide and often overlapping morphological spectrum, brought on
not only by the number of different structures within the hair
follicle but also by the hair follicle cycle. These characteristics of
the hair follicle often make follicular tumours difficult to under-
stand to the beginners in the field, and sometimes result in
considerable diagnostic difficulties for the practicing pathologist.
General diagnostic considerations
The most important diagnostic task is to determine whether a
follicular tumour is benign or malignant and, if malignant,
whether it is prone to recur or metastasize (fortunately, the latter
being quite rare). Architectural (infiltrative vs. circumscribed)
and cytological features (high mitotic count, pleomorphism) are
quite useful for this categorization, yet not sufficient alone
without a thorough knowledge of specific entities.
Hair anatomy/embryology-based classification of follicular
tumours facilitates the diagnosis because the nomenclature of
follicular tumours is descriptive and sometimes inconsistent. It is
a classification that categorizes the entities based on the
anatomic part of the follicle whose morphology they recapitulate.
There are essentially four parts of the follicle from deep to su-
perficial: the hair bulb, the suprabulbar zone (the stem), the
isthmus and the infundibulum.2
The suprabulbar zone extends
between the bulb and the insertion of arrector pili muscle. It is
followed by the isthmus whose upper limit is the opening of the
sebaceous duct. The infundibulum is the uppermost part of the
follicle, spanning the distance between the sebaceous duct
opening and the epidermal surface.
There are several classifications3,4
which are fundamentally
quite similar, with most differences being in the number of cat-
egories. For the purpose of this review, we will use a relatively
simple division into 5 categories, based on the predominant
pattern of differentiation, starting from the most superficial part
of the follicle:
- tumours with infundibular differentiation
- tumours with isthmic differentiation
- tumours with trichilemmal (outer root sheath of the hair
stem bulb) differentiation
- tumours with hair bulb (matrical and biphasic)
differentiation
- tumours with panfollicular differentiation.
Tumours with infundibular differentiation
The infundibulum is characterized by epidermal-resembling
keratinocytes (containing a palisaded basal layer, a spinous
and a granular layer) and laminated keratin. We will focus on
trichoadenoma, as other entities in this group are cysts or
hamartomas and not truly neoplastic (dilated pore, naevus
comedonicus).
Trichoadenoma, also called “trichoadenoma of Nikolowski”,5
is a collection of keratinous dermal cysts, typically well-
circumbscribed, with little variation in cyst size (Figure 1). It
bears an adenoma-like architecture on scanning power, but has
no glandular components and is clearly not an adenoma. Cysts
are filled with laminated infundibular keratin, and the epithelium
contains all epidermal layers. Occasionally, the epithelium may
be composed of pale pink isthmus-like cells and the keratin is
more compact, or the surface of cysts is somewhat crenulated
resembling the sebaceous duct. A foreign-body granulomatous
reaction surrounding the cysts is frequent. The tumour is entirely
benign in behaviour.
The main differential diagnoses are microcystic adnexal car-
cinoma (MAC) and desmoplastic trichoepithelioma (DTE). Some
MACs are associated with larger cysts containing laminated
keratin, resembling trichoadenoma at first glance; however, MAC
is a deeply infiltrative tumour with desmoplasia that shows a
substantial proportion of tumour strands and solid cell aggre-
gates. Care should be taken to avoid this misdiagnosis, as treat-
ment for MAC requires extensive surgery. DTE shows some cysts
with infundibular-type keratin. However, follicular germ papilla-
like structures are also identified and the stroma in the back-
ground is desmoplastic.
Tumours with isthmic differentiation
The isthmic portion of the follicle is characterized by an outer
palisaded layer and 4e5 inner layers of pink keratinocytes
without a well-developed granular cell layer, while the keratin is
Zlatko Maru
si
c MD PhD Department of Pathology, University Hospital
Center Zagreb, Zagreb, Croatia. Conflicts of interest: none declared.
Eduardo Calonje MD Dip RCPath Director of Diagnostic
Dermatopathology, Department of Dermatopathology, St John’s
Institute of Dermatology, St Thomas’ Hospital, London, UK. Conflicts
of interest: none declared.
MINI-SYMPOSIUM: DERMATOPATHOLOGY
DIAGNOSTIC HISTOPATHOLOGY 26:3 128
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under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).

2. compact and homogenous (so-called “trichilemmal”), as
opposed to laminated infundibular keratin.
Tumours with isthmic differentiation include the tumour of
the follicular infundibulum (anatomically, a misnomer), pilar
sheath acanthoma and proliferating trichilemmal cyst (pilar
tumour).
Tumour of the follicular infundibulum (TFI)6
most
frequently presents as a solitary scaled nodule in the head and
neck of middle-aged and elderly persons. On histology, it is a
fenestrated proliferation of keratinocytes with isthmic features,
connected to the epidermis (Figure 2a). The epithelial strands
that outline fenestrations are often arranged parallel to the skin
surface. The behaviour is benign.
Dermal induction changes accompanying dermatofibroma
and epithelial fenestrations in fibroepithelioma of Pinkus may
resemble TFI. In cases with underlying dermatofibroma, TFI
should not be diagnosed. Fibroepithelioma of Pinkus is distin-
guished from TFI based on its hair germ differentiation.
Pilar sheath acanthoma (PSA)7
presents as a solitary small
nodule with a central keratin pore, characteristically on the upper
lip. Histologically, there is a cystic central indentation with
infundibular appearance surrounded by well-circumscribed
nodules of isthmic keratinocytes containing trichilemmal kera-
tin (Figure 2b). Its behaviour is entirely benign.
Trichofolliculoma architecturally resembles PSA, but it shows
more lines of differentiation (panfollicular differentiation).
Sometimes, the central cystic part is not present in the sections
due to orientation/tangentional sectioning. When the latter
happens, well-circumscribed nodules with isthmic keratinocytes
surrounding compact keratin should allow for the diagnosis of
PSA to be made.
Proliferating trichilemmal cyst (PTC, synonym ¼ pilar
tumour) shows scalp predilection (around 90% of cases) and a
marked female predominance.8
Its biologic potential spans from
benign (majority of cases) towards atypical/low grade, and rare
higher grade tumours. They are slowly growing, usually solitary,
often large and multinodular, with deep extension. Some cases
exhibit substantial ulceration and a rather dramatic clinical
appearance. Histology suggests development from a simple tri-
chilemmal cyst in many cases. Architecturally, lobulated solid
tumor foci predominate over the cystic component. In benign
cases, tumour outlines are smooth, pushing, without infiltrative
growth (Figure 2c). There is typically no granular cell layer and
central keratin is compact and homogeneous. Epithelial glycogen
accumulation can be seen, as well as a foreign body-type reaction
in the surrounding connective tissue.
A smaller proportion of cases have some malignant potential.
In the largest study to assess malignant potential so far, Ye et al.9
stratified 76 pilar tumour cases with follow-up into three groups.
The first group, consisting of tumours with moderate atypia,
typical pushing growth and no invasive features showed entirely
benign behaviour. The second group exhibited some locally
infiltrative dermal/subcutaneous growth (no neural/vascular
involvement or significant atypia) and had local recurrence in
15% of cases. Third group were tumours that showed marked
nuclear atypia, atypical mitoses, necrosis and infiltrative growth
pattern (including but not limited to cases with neural and
vascular involvement). They were the least frequent and showed
higher rates (50%) of recurrence/regional lymph node metas-
tasis. In this case series no distant metastases were recorded.
There have been some convincing reports describing extremely
rare death from metastases10
; however, there are also several
sporadic reports of visceral metastasis that lack convincing his-
tological depiction.
Tumours with trichilemmal differentiation
For the purpose of this review, “trichilemmal” refers to differ-
entiation recapitulating the outer root sheath of the hair stem
bulb. It is characterized by several layers of cells with pale to
clear, glycogenated cytoplasm, surrounded by a palisaded cell
layer with nuclei oriented opposite to a brightly eosinophilic
basement membrane.
Trichilemmoma can be solitary or multiple. Multiple trichi-
lemmomas are diagnostic of Cowden syndrome, an autosomal
dominant multiple hamartoma syndrome associated with germ-
line mutations in the PTEN tumor suppressor gene.11
Individuals
with Cowden syndrome carry an increased risk of breast, thy-
roid, uterine and other malignancies. Besides multiple trichi-
lemmomas, the condition is also characterized by a host of
cutaneous lesions such as multiple acrochorda, acral keratosis,
dermal hyperneury and vitiligo. Oral cavity is frequently affected,
imparting a characteristic, diffuse cobblestone mucosal appear-
ance. Solitary trichilemmoma is most frequent in the head and
neck, especially the central part of face. It is composed of
peripherally palisading clear cells with epidermal/hair follicle
connection and smooth contours outlined by a brightly eosino-
philic basement membrane (Figure 3a). Trichilemmoma is
practically the only cutaneous epithelial tumour known to
diffusely express CD34, which can be important in the differen-
tial diagnosis.
Desmoplastic trichilemmoma12
is a variant that has no asso-
ciation with Cowden syndrome. It is very important because it is
a mimicker of malignancy. The periphery of the lesion looks like
a typical trichilemmoma, while the center is sclerosed, composed
of narrow and irregular epithelial cords embedded in a densely
hyalinized PAS-positive, diastase-resistant stroma (Figure 3b).
The cells in the desmoplastic areas have a more squamoid
appearance.
Due to its infiltrative growth, desmoplastic trichilemmoma
needs to be distinguished from trichilemmal, squamous and
basal cell carcinoma. The pseudo-infiltrative part of desmoplastic
trichilemmoma is central, not peripheral as in carcinomas, the
Figure 1 Trichoadenoma. Multiple dermal cysts filled with infundibular-
type keratin.
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3. epithelial cords are surrounded by hyalinized stroma and do not
exhibit true cytological atypia. Additionally, the periphery ex-
hibits typical trichilemmoma features. In doubtful cases, espe-
cially in shave biopsies, CD34 can be very useful in the
distinction, as carcinomas are negative for this marker. However,
caution is necessary as some or most of the squamoid cells in the
desmoplastic area can be negative for CD34. Classical trichi-
lemmoma is most commonly confused with eccrine tumours
such as hidroacanthoma simplex and eccrine poroma. Lack of
ductal differentiation (which can be confirmed by negative
reaction for EMA and CEA) and presence of trichilemmal dif-
ferentiation should allow distinction to be made.
Trichilemmal carcinoma (TC) is regarded by some au-
thors13,14
as a clear cell variant of squamous cell carcinoma, and
the original concept proposed by Headington15
is contested.
However, the neoplasm is recognized in the WHO classification
of skin tumours. TC is relatively rare and found in the sun-
exposed skin of the elderly. Histologically, it shows a lobular
growth of atypical, PAS-positive clear cells with occasional sub-
nuclear vacuolization and connection to hair follicles, but no
Figure 2 a) Tumour of the follicular infundibulum. Anastomosing epithelial strands connected to the epidermis; (inset) isthmic-type epithelium. b)
Pilar sheath acanthoma. Nodules of isthmic-type epithelium with central keratin (inset). c) Proliferating trichilemmal tumour. Well-circumscribed,
predominantly solid tumour with central trichilemmal keratin; (inset) homogeneous keratin and isthmic-type epithelium.
Figure 3 a) Trichilemomma. Warty architecture with hyperkeratosis; (inlet) trichilemmal differentiation in the form of clear, peripherally palisading
cells surrounded by a thickened basement membrane. b) Desmoplastic trichilemmoma. Outline of typical trichilemomma with a sclerotic center;
(inset) central part, narrow epithelial cords in a hyalinized stroma. c) Trichilemmal carcinoma. Nodules composed of atypical cells with trichilemmal
differentiation.
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nd/4.0/).

4. thickening of the basement membrane (Figure 3c). Nucleoli are
prominent, mitoses are frequent, and there are foci of trichi-
lemmal keratinization. There can be focal CD34 expression,
consistent with outer root sheath differentiation. TC typically
exhibits low-grade behaviour, therefore a tumor-free margin is
very important.
TC needs to be distinguished from desmoplastic trichi-
lemmoma, and also from clear cell hidradenocarcinoma. The
latter is more aggressive in behavior and shows ductal differen-
tiation highlighted by CEA and/or EMA staining. Desmoplastic
trichilemmoma lacks pleomorphism and mitoses exhibited by
TC.
Tumours with hair bulb differentiation
The hair bulb consists of a crescent-shaped epithelial part - the
matrix, which encases a central collection of mesenchymal cells -
the follicular papilla. A layer of palisading follicular germinative
epithelial cells in close association to papilla mesenchymal cells
is found at the matrix/papilla interface. Tumours recapitulating
the hair bulb can be divided into 2 categories. One represents the
matrix (pilomatrixoma, melanocytic matricoma), and the other is
biphasic epithelial/mesenchymal (trichoepithelioma, tricho-
blastoma), corresponding to the juxtaposed follicular germina-
tive and mesenchymal cells of the papilla.
Pilomatricoma16
is usually encountered in children and
young adults in the head/neck, trunk and upper limbs. Most
pilomatricomas are solitary. Multiple pilomatricomas have been
documented in patients with Gardner syndrome, Turner syn-
drome, and a host of other very rare syndromes17
It is usually
multilobulated, dermal, occasionally subcutaneous. There are
two cell populations - small and uniform basaloid cells with
larger vesicular nuclei, and eosinophilic “ghost” cells with
pyknotic or faintly visible/absent nuclei (Figure 4a). Basaloid
cells predominate in early lesions. They occupy the periphery
and gradually transform into central ghost cells. Mitotic activity
is usually brisk and this should not be regarded as a sign of
malignancy. Foreign-body type histiocytic reaction and central
calcification can be encountered. The latter is especially frequent
in late lesions, with true osseous metaplasia and formation of
marrow spaces particularly in long-standing tumours. Prolifer-
ating pilomatricoma is defined as a variant in which basaloid
cells make the bulk of the tumour with hardly any or only a small
proportion of ghost cells.
Melanocytic matricoma1
is a rare tumour with bulb differ-
entiation, melanin deposits and numerous pigmented
dendrocytic melanocytes. It bears some resemblance to piloma-
tricoma, with less prominent ghost cells.
Pilomatrical carcinoma (Figure 4c) is found in same
anatomic sites and older population than pilomatricoma. A
number of reported cases are likely to represent misdiagnosed
early pilomatricomas with brisk mitotic activity. Features suspi-
cious for malignancy are large size, deep/infiltrative growth,
confluent tumour necrosis, venous, lymphatic or perineural in-
vasion. Interestingly, both pilomatricoma and pilomatrical car-
cinoma exhibit mutations in the beta-catenin gene CTNNB1.18
It
appears that most cases pilomatrical carcinoma are low grade
tumours, with rare metastases that are usually limited to the
lymph node drainage area. However, a handful of cases reported
in the literature have been associated with distant metastases.19
Trichoepithelioma and trichoblastoma. These tumours show
substantial morphological overlap and it has even been sug-
gested that all neoplasms in this category should be classified as
trichoblastomas. In general, “trichoepithelioma” is used for more
superficial sporadic tumours and multiple small tumours located
on the face that are part of the Brooke-Spiegler syndrome.
Trichoepithelioma is usually limited to the upper portion of
the reticular dermis and may show occasional epidermal
connection. It is composed of small lobules and infundibular
keratocysts lined by basaloid, peripherally palisading cells which
are cytologically essentially indistinguishable from BCC cells
(Figure 5a). The surrounding stroma is generally more pro-
nounced than in BCC, recapitulating “papillary mesenchymal
bodies”, i.e. mesenchymal nodules forming the follicular hair
germ papilla.
Multiple trichoepitheliomas occur as small papules in the
central face, characteristically occupying nasolabial folds,
cheeks, eyebrows or eyelids. They are found in multiple familial
trichoepithelioma setting as an isolated finding, or accompanying
cylindromas/spiradenomas in Brooke-Spiegler syndrome. Multi-
ple familial trichoepithelioma is actually a phenotypic variant of
Brooke-Spiegler syndrome, as they share both clinical/pathologic
features and CYLD mutations.20
Rombo syndrome is a rare syn-
drome that may present with multiple trichoepitheliomas in
combination with milia, vermiculate atrophy, BCC, vellus hair
cysts, peripheral vasodilatation, and cyanosis.1
The main differential diagnosis for trichoepithelioma is BCC.
Formation of papillary mesenchymal bodies points to trichoepi-
thelioma, while ulceration, connection to the epidermis, peri-
tumoural clefts and mucin deposition argue for BCC. Numerous
Figure 4 a) Pilomatricoma. Proliferation of peripheral basaloid and central ghost cells; (inset) interface between two cell populations. b) Pilomatrical
carcinoma. Poorly differentiated carcinoma with ulcerated surface, composed of basaloid cells; (inset) a high power view highlighting ghost cells
surrounded by atypical basaloid cells with numerous mitoses.
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5. studies have tried to utilize various panels of immunohisto-
chemical markers, such as CD34, CD10, epithelial membrane
antigen, bcl-2, cytokeratin 15, cytokeratin 20 and D2-40 to aid in
the distinction, with inconclusive results.21
If histological
distinction cannot reliably be made on a superficial shave biopsy,
it is prudent to recommend complete excision of the lesion.
Desmoplastic trichoepithelioma (DTE) shows some specific
morphological and differential diagnostic features compared to
conventional trichoepithelioma. It is usually a small and super-
ficial papule with a central dimple located on the face of young
adults. Lesions are superficial, fairly circumscribed and charac-
terized by superficial infundibular keratocysts with focal calcifi-
cation and thin strands of epithelial basaloid cells lacking
peripheral palisading, embedded in a desmoplastic stroma
(Figure 5b). Perineural involvement has rarely been reported in
DTE22
that should not be equated with malignancy or lead to
overtreatment.
The main differential diagnoses which can be extremely
challenging in superficial partial biopsies, include morphoeic
BCC (mBCC) and microcystic adnexal carcinoma (MAC). DTE
does not show any peripheral palisading, retraction artefact,
prominent mitotic activity or ulceration found in mBCC and
contains keratocysts, unlike mBCC. DTE can also be distin-
guished from mBCC by the presence of scattered CK20-positive
Merkel cells in tumour strands and negativity for androgen re-
ceptors. BerEP4 is not useful in the differential, being usually
positive in both. DTE is never as infiltrative as MAC, even in the
cases with perineural invasion described by McNiff et al.22
In
addition, MAC usually does not exhibit superficial calcified ker-
atocysts. Evidence of ductal differentiation in MAC by CEA/EMA
staining, if present, can exclude DTE. A combination of CK15 and
CK19 may also be used in the differential, as the immunoprofile
is CK15þ/CK19- in DTE and CK15-/CK19þ in MAC.23
Trichoblastoma has a predilection for the head and neck,
trunk, genital/perianal region and proximal extremities. It can be
large (3 cm or more), is well-circumscribed and occupies the
entire dermis with occasional subcutaneous involvement. It has
follicular hair germ differentiation, i.e. has both epithelial and
mesenchymal component. The epithelial component grows in
larger/smaller nodules, cribriform or trabecular structures, sur-
rounded by specialized mesenchymal cells resembling the cells
of follicular papilla (Figure 5c). Conventional BCCs do not show
such typical epithelial/mesenchymal juxtaposition and marked
peri-epithelial mesenchymal cell condensation. Trichoblastoma
follows a benign course. Interestingly, Requena et al. recently
described a multiple facial plaque trichoblastoma variant of
presumed hereditary aetiology, but were unable to track down an
underlying genetic alteration.24
Malignant variants may occur
and are described below.
Cutaneous lymphadenoma25
(synonym adamantoid tricho-
blastoma) is a characteristic morphological subtype of tricho-
blastoma. It is well-delineated, un-encapsulated, with nests of
large clear cells that are surrounded by peripheral palisading
cells, infiltrated by numerous lymphocytes and embedded in a
dense fibrous stroma. It should not be confused with lymphoe-
pithelial carcinoma of the skin, an epithelial malignancy heavily
infiltrated by lymphocytes.
Malignant trichoblastoma can have a malignant epithelial
(trichoblastic carcinoma) or mesenchymal (trichoblastic sar-
coma) component, or a combination of the two (trichoblastic
carcinosarcoma) (Figure 5d). All of them affect the elderly.
Sarcomatous transformation is even less frequent than carci-
nomatous transformation, with only a handful of cases
described so far.26
“Trichoblastic carcinoma” has been used by
the late Bernard Ackerman as a synonym for BCC3
; however,
Figure 5 a) Trichoepithelioma. Superficially-centered tumour composed of small germinative nests; (inset) formation of abortive hair germ
structures. b) Desmoplastic trichoepithelioma. Superficial, non-infiltrative tumour composed of cords, small nests and calcified microcysts sur-
rounded by a dense fibrous stroma. c) Trichoblastoma. Nests resembling hair germ structures surrounded by characteristic mesenchymal
component. d) Trichoblastic carcinosarcoma. Tumour harbouring both epithelial and mesenchymal malignant components; (inset) high power view
showing atypia in the mesenchymal component as well as brisk mitoses in the epithelial component.
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nd/4.0/).

6. we and other authors use it for malignant transformation of
trichoblastoma. The most important diagnostic feature of ma-
lignant trichoblastoma is its grade. Low grade tumours
resemble trichoblastoma but have infiltrative growth, involving
deep soft tissue or skeletal muscle; high grade trichoblastic
carcinomas show high grade cytomorphology together with
infiltrative growth. The data on these two tumour types is
limited, but it seems that low grade tumours exhibit only local
recurrence, while high grade tumours may result in metastasis
and death.27
As Brooke-Spiegler syndrome has been mentioned in this
section, we will also refer to Birt-Hogg-Dub
e (BHD) syndrome,28
a rare autosomal-dominant genodermatosis characterized by
numerous, discrete 1e5 mm skin-coloured papules on the head
and neck. It is caused by mutations in the FLCN gene29
that
simultaneously carry predisposition for renal tumours, pulmo-
nary cysts, bullous emphysema and spontaneous pneumothorax.
Histology of the papules corresponds to fibrofolliculoma, a cir-
cumscribed proliferation of loose connective tissue around a
well-formed follicle, and trichodiscoma, a collection of loosely-
woven, follicle-associated connective tissue with admixed thin-
and thick-walled blood vessels.
Tumours with panfollicular differentiation
Several differentiation lines can be found to a small extent in
various follicular tumours; in tumours with panfollicular differ-
entiation, it is a rule and it is generally quite pronounced. They
are therefore considered hamartomatous by most authors.
Trichofolliculoma30
usually presents in the head and neck as
a small (0.5e1 cm), solitary flesh-coloured nodule. One or more
central white silky hairs can be seen growing from the nodule.
On histology, a central cystic cavity is lined by infundibular type
epithelium, and contains keratinous debris/shredded hairs.
Numerous hair follicles with various anatomic lines of differen-
tiation are spreading from the lining of the cavity towards the
surrounding dermis (Figure 6). Trichofolliculoma not only re-
capitulates various anatomical lines of differentiation, but also
different phases of follicle growth (anagen, catagen, telogen). Its
behaviour is entirely benign. An extremely rare tumour called
panfolliculoma can be included in this group because it shows
multiple elements of the hair follicle, yet it predominantly
resembles trichoblastoma with areas of more mature follicular
differentiation. A
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Figure 6 Trichofolliculoma. Symmetrical cystic indentation giving rise
to numerous small follicles that show several lines of follicular
differentiation.
Practice points
C Follicular tumours are rare and the terminology is confusing
C A tumour classification based on anatomical lines of follicular
differentiation is useful
C Follicular tumour diagnosis may seem difficult, but is achievable
with proper knowledge of the classification
C Mitotic activity or infiltrative growth do not equal malignancy.
Knowledge on which benign entities may display such features is
crucial to prevent misdiagnosis
C Multiple follicular tumours can be associated with genetic cancer
tumour syndromes
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Ó 2020 The Authors. Published by Elsevier Ltd. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
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