Vol.:(0123456789)
1 3
Head and Neck Pathology
https://doi.org/10.1007/s12105-018-0939-x
ORIGINAL PAPER
Poorly Differentiated Clusters Predict a Poor Prognosis for External
Auditory Canal Carcinoma
Masaru Miyazaki
1,2
· Mikiko Aoki
1
· Yasuko Okado
1,2
· Kaori Koga
1
· Makoto Hamasaki
1
· Fumiaki Kiyomi
4
·
Toshifumi Sakata
2
· Takashi Nakagawa
3
· Kazuki Nabeshima
1
Received: 5 April 2018 / Accepted: 24 May 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is rare and offers a poor prognosis; more accurate
prognostic biomarkers are required. Our laboratory recently demonstrated that tumor budding, characterized by tumor cell
clusters (< 5 cells), and laminin 5-γ2 staining of SCC of the EAC are associated with shorter survival. However, clusters
composed of ≥ 5 tumor cells are also found in the stroma. Previous reports of colorectal cancer suggest that poorly differenti-
ated clusters (PDCs) are a negative prognostic indicator. Here, we report on the association between PDCs and prognosis in
SCC of the EAC. PDCs and tumor budding were histopathologically and immunohistochemically (cytokeratin AE1/AE3)
analyzed in 31 cases of pre-treatment biopsy SCC of the EAC. Clusters in the stroma composed of < or ≥ 5 cancer cells
were defined as tumor budding or PDCs, respectively. Entire tumors were initially scanned to identify greatest PDC density.
Tumors with low or high PDC density were classified as low- and high-grade, respectively. Patients with high-grade PDCs
had a significantly poorer outcome than those with low-grade. Even in cases of low-grade tumor budding, those with high-
grade PDCs had a poor prognosis. Multivariate analysis results indicated that high-grade PDCs were associated with poor
prognosis. PDC grade can provide a more accurate prognosis than tumor budding in SCC of the EAC.
Keywords Clustered tumor cell · Neoplasm invasion · Squamous cell carcinoma · External auditory canal
Introduction
The external auditory canal (EAC) is a small area including
an outer cartilaginous portion, comprising one-third to one-
half of its length, and an inner bony or osseous portion [1].
Stratified squamous epithelium on the EAC and tympanic
membrane is known to be unique in its ability to migrate
from the tympanic membrane outward, since this migratory
phenomenon has not been observed in the squamous epi-
thelium of other organs including skin, oral cavity, esopha-
gus, and the uterine cervix [2–4]. Squamous cell carcinoma
(SCC) arising from the unique epithelium of the EAC is a
rare, aggressive cancer with a poor prognosis [5, 6]. The cur-
rent 5-year disease-specific survival of stage I, II, III, and IV
are 94.8, 78.9, 68.3, and 22.9%, respectively [7]. Aggressive
surgery is needed for patients with advanced disease, but it
also causes severe complications that impair patient quality
of life [5, 8]. In order to improve these prognoses and patient
quality of life, an accurate staging system that can formu-
late treatment strategy is needed. The revised University of
Pittsburgh TNM staging system is commonly used during
prognosis [9]. However, there are some patients with tumors
that recur locally despite their categorization as low-risk
and, conversely, some patients have longer survival times
despite their categorization as high-risk [8]. For more accu-
rate assessment of these patients with intermediate-stage
tumors, a search for morphologic or molecular biomarkers
that reflect the biological characteristics of SCC-EAC and
patient outcome prediction is needed [10].
* Kazuki Nabeshima
kaznabes@fukuoka-u.ac.jp
1
Department of Pathology, Fukuoka University Hospital
and School of Medicine, 7-45-1 Nanakuma, Jonan-ku,
Fukuoka 814-0180, Japan
2
Department of Otorhinolaryngology, Fukuoka University
Hospital and School of Medicine, Fukuoka, Japan
3
Department of Otorhinolaryngology, Graduate School
of Medical Sciences, Kyushu University, Fukuoka, Japan
4
Academia, Industry and Government Collaborative Research
Institute of Translational Medicine for Life Innovation,
Fukuoka University, Fukuoka, Japan
@Phil_Robichaud
@deepthiw
@JoseServera