Fine-needle aspiration (FNA) biopsy: Historical aspects

Department of Cytopathology, Naval Hospital of Athens, Athens, Greece.
Folia Histochemica et Cytobiologica (Impact Factor: 1.36). 12/2009; 47(2):191-7. DOI: 10.2478/v10042-009-0027-x
Source: PubMed


This study aims to present the origins and the historical evolution of fine-needle aspiration biopsy and to also underline its importance in the history of modern cytology. The article focuses on the advances made in the 20th century that have led to the modern techniques associated with the procedure. The authors conducted a thorough review of early reports on needle biopsy, particularly those published during 19th and 20th century, examining in brief also the origins of the needle biopsy. The first report on the use of needle puncture is referred in early writings of Arab medicine. In the early 20th century, Martin and Ellis are considered to be the founders of modern needle aspiration techniques. The German doctor Mannheim was the first to publish reports suggesting the use of fine needles with a small gauge. The establishment and world-wide expansion of FNA should be attributed to the representatives of the Swedish School of Cytopathology. The school embraced FNA in the second half of the 20th century while serving as a training ground for doctors around the world. The history of needle biopsy spans ten centuries. However, the development and establishment of the technique in its modern form took place primarily during the twentieth century. Today, FNA is considered an important cytologic technique with sufficient diagnostic accuracy, especially when applied in cases of lung and prostate cancer.


Available from: Emmanouil Magiorkinis, Aug 21, 2014
©Polish Histochemical et Cytochemical Society
Folia Histochem Cytobiol. 2009:47(2): 191 (191-197)
doi: 10.2478/v10042-009-0027-x
Fine-needle aspiration (FNA) biopsy is the study of
cells obtained by puncturing organs of human body
with the use of small-gauge needle [1]. Doctors usual-
ly perform the procedure after detection of a mass
lesion through imaging methods such as ultrasound
tomography, CT or MRI [2]. The process of aspiration
biopsy involves the puncture of the lesion with the use
of a fine needle (22-gauge needle) of various lengths
(from 5 cm to 20 cm) with external diameters between
0.6 mm and 1.0 mm [2]. Aspiration biopsy cytology
currently constitutes a separate branch of diagnostic
cytology [3,4]. The main philosophy of aspiration biop-
sy cytology differs greatly from exfoliative cytology,
since that procedure focuses on cells that have been
scraped or peeled from epithelium or mesothelium. The
history of the technique needle biopsy spans a period of
over 10 centuries (Table 1), whereas FNA undergone a
great deal of improvements during the last century. This
article will document the development of FNA tech-
niques during the 20
The first use of needle for the diagnosis and
treatment of various diseases.
The first report on the use of needles for therapeutic
purposes can be found in Arab medicine, in the writ-
ings of Albucasis or Abu al-Qasim Khalaf ibn al-
Abbas Al-Zahrawi as it was his Arab name (936-1013
A.D), court physician to the caliph of the Andalusia,
Al-Hakim II. In his famous treatise, Kitab al-Tasrif
(The Method of Medicine), the most influential book
of Arab Medieval Medicine, Albucasis described for
the first time therapeutic punctures of the thyroid
gland, using instruments resembling modern aspiration
needles [5-7]. Albucasis' description resembles a mod-
ern FNA of the thyroid gland [8]:
"This tumor, which is called 'Elephant of the
throat,' is a large tumor the color of the body; it com-
monly occurs in women. It is of two kinds, congenital
and acquired. There is no treatment for the congenital
type. The acquired type consists of two kinds: one
resembles a sebaceous cyst while the other resembles
a tumor arising from an arterial aneurysm. The latter
is dangerous to incise, so never you apply a knife to the
latter kind unless the tumor is very small. If you try to
explore them with a probe and find they are like seba-
ceous cysts and not attached to any blood vessel, then
Vol. 47, No. 2, 2009
pp. 191-197
Fine-needle aspiration (FNA) biopsy: historical aspects
Aristidis Diamantis
, Emmanouil Magiorkinis
, Helen Koutselini
Department of Cytopathology, Naval Hospital of Athens, Athens, Greece
Associate Professor, Department of Pathology and Cytopathology, Henry Dunant Hospital, Athens, Greece
Abstract: This study aims to present the origins and the historical evolution of fine-needle aspiration biopsy and to also
underline its importance in the history of modern cytology. The article focuses on the advances made in the 20
century that
have led to the modern techniques associated with the procedure. The authors conducted a thorough review of early reports
on needle biopsy, particularly those published during 19
and 20
century, examining in brief also the origins of the needle
biopsy. The first report on the use of needle puncture is referred in early writings of Arab medicine. In the early 20
ry, Martin and Ellis are considered to be the founders of modern needle aspiration techniques. The German doctor
Mannheim was the first to publish reports suggesting the use of fine needles with a small gauge. The establishment and
world-wide expansion of FNA should be attributed to the representatives of the Swedish School of Cytopathology. The
school embraced FNA in the second half of the 20
century while serving as a training ground for doctors around the world.
The history of needle biopsy spans ten centuries. However, the development and establishment of the technique in its mod-
ern form took place primarily during the twentieth century. Today, FNA is considered an important cytologic technique with
sufficient diagnostic accuracy, especially when applied in cases of lung and prostate cancer.
Keywords: aspiration biopsy, history, cytopathology, diagnostic cytology, needle aspiration
Correspondence: E. Magiorkinis, Leoforos Aianteiou
3-PB 1541 ; tel.: (+30210) 4677549, fax.: (+30210) 7261307,
Page 1
immediately cut down upon them as you would a cyst
and remove them with whatever capsule may surround
them, as long as they are contained within a capsule. If
not, dissect away the whole accurately; then treat the
place with suitable remedies."
Kitab Al-Tasrif was considered a medical ency-
clopaedia concerning surgery. The 10
-century text
contains figures of numerous surgical instruments and
even medical needles. Some of the needles are clearly
hollow, representing the first documented needles in
the history of Medicine. The work by Albucasis was so
influential that his book was translated into Latin by
Gerard of Cremona (1114-1187 A.D.), a famous trans-
lator of Arab scientific works. The French surgeon and
"Restorer of Surgery," Guy de Chauliac (1300-1368
A.D.), in his famous book "Inventarium Sive Chirurgia
Magna" quoted the work of Albucasis more than 200
times [9].
Needle biopsy in the twentieth century:
The founders of the fine needle aspiration
(FNA) technique
During the 19
century, and the beginning of the 20
century, the use of surgical needles for the diagnosis
and treatment of various diseases was widely used
In 1912, a German haematologist, Hans Hirschfeld
(1873-1944), reported the first needle aspiration biop-
sy by reporting the diagnosis of cutaneous lymphomas
and other tumors with the use of needle aspiration
biopsy and histological process of the acquired cellu-
lar material [17]. In his paper entitled 'Über isolierte
aleukämische Lymphadenose der Haut', he described
his technique in a very detailed way (translated in Eng-
lish): "One of the largest facial tumors is punctured. It
is not possible to aspirate any fluid and so the blood
drops emerging from the puncture are taken for dry
preparation on a slide. Staining with May-Giemsa pro-
duced their picture..." [17]. Hirschfeld described the
use of small tissue samples that were excised from the
tumors and then fixed in formol and stained with vari-
ous staining methods.
Gordon Ward, a British haematologist and medical
officer in the British Army, improved and expanded
the method in 1914 to diagnose lymphoblastoma [18].
Hirschfeld also extended his investigations to other
tumors and published his observations in 1919 [19].
In 1916, Anastasios Aravandinos, professor of
Internal Medicine in Athens University, designed
a needle for the safe procedure of spleen puncture and
the quick aspiration of cellular material [20]. Similar
punctures were performed during his time for the diag-
nosis of non-neoplastic liver lesions (i.a. cysts) as well
as for the diagnosis and therapy of liver abscesses for
tropical diseases, such as histolytic amoeba infection.
While working at John Hopkins Hospital in Balti-
more, Guthrie, performed a systematic study of cellu-
lar smears from lymph node puncture in 1921 [21]. He
used a 21-gauge needle for aspiration biopsy and coat-
ed aspirates on glass slides forming cell films that were
air dried and stained with Romanowksy staining.
Guthrie reported that the method allowed him to suc-
cessfully diagnose various diseases such as syphilis,
tuberculosis, malignant lymphoma, leukemia and
metastatic carcinoma [21].
Leonard Stanley Dudgeon (1876-1938), a patholo-
gist working at St Thomas' Hospital in London and
Professor of Pathology in University of London, was
the first to scientifically establish the technique of nee-
dle biopsy [22,23]. Dudgeon's motive was the need to
establish a fast and secure diagnosis of histological
preparations. He mounted tissue material from surgi-
cal biopsies to glass slides by using touching smears or
imprints. In his paper with Vincent Patrick [22], a res-
ident assistant surgeon in St. Thomas Hospital, they
reported 300 cases with a diagnostic accuracy of 97
percent. They describe a total of 9 erroneous diagnoses
of which six occurred from the first 100 samples, and
three in the second 100 samples; the erroneous cases
included two cases of ulcers of the lower lip (a septic
ulcer and an actual carcinoma), one case of a node iso-
lated from peritoneum, two cases of lymphatic glands
which were examined for metastatic carcinoma and
four cases of breast tumors. His later study with Nor-
man Barrett (1903-1979), an Australian-born British
surgeon at St. Thomas Hospital, in 1934 [23] focused
mainly on the cytology of scrapings from 1.000,surgi-
cal specimens. In this study, Dudgeon concentrated on
the possibility of identifying malignant cells in sputum
using smears fixed with Schaudinn's solution and
stained with haemalum and eosin. Over time, he per-
fected this technique. In a later paper with C.H.
Wrigley, [24] he presented a positive detection rate of
68 percent in a lung cancer study, finding malignant
cells in the sputum in 26 out of 38 cases.
Two researcher groups in the United States [25-27],
Bradley Coley with Sharp and Hayes Martin with
Edward Ellis (1877-1954), worked independently on
the same method at the Memorial Hospital in New
York City.
Independently from each other, the two groups
began experimenting on a large scale with aspiration
biopsy of various human tumors in the late 20s. In
a personal letter to Koss, [28] Dr. Fred W. Stewart said
that Dr. James Ewing (1866-1943), chief of pathology
at Memorial Hospital, initially opposed incision biop-
sies of cancers because of his firm belief that the
procedure considerably increased the risk of spread of
the disease. In fact, during Ewing's tenure as a direc-
tor of the Memorial Hospital, open biopsies of subcu-
taneous tumors, whether primary or metastatic, were
A. Diamantis et al.
©Polish Histochemical et Cytochemical Society
Folia Histochem Cytobiol. 2009:47(2): 192 (191-197)
doi: 10.2478/v10042-009-0027-x
Page 2
prohibited [29]. Stewart, the successor of Ewing,
wrote that: "The needle evolved as a sort of compro-
Both Martin and Coley were reluctant to treat
patients without a firm diagnosis, so aspiration biopsy
evolved as a method to diagnose cancer without cut-
ting invasive surgery. Martin and Ellis also wanted to
combine cellular and histological findings and also
simplify the method for studying biopsy specimens. In
the early thirties, they applied their technique on
breast, thyroid gland and stomach carcinomas, as well
as myelocytomas and non-neoplastic diseases [26,27].
After infiltration with 1 percent novocaine, the proce-
dure consisted of a small incision over the lesion with
the use of a scalpel (No. 11 Bard Parker blade), fol-
lowed by aspiration with an 18-gauge needle attached
to a 20-ml Record syringe. The aspirated cellular mate-
rial was smeared on glass slides, air-dried and stained
with hematoxylin and eosin (immediate method).
Fragments of tissue obtained by the procedure were
removed, placed on a piece of blotting paper (a so-
called "clot"), fixed in formalin and processed as
a usual biopsy (longer method) [26-28]. The immedi-
ate method, yielded tissue samples in 80 percent of the
cases, with a total of 65 cases identified with cancer;
60 percent of them were also confirmed by histologi-
cal diagnosis. In the conclusions of their paper, Martin
and Ellis [26] refer to the advantages and the disad-
vantages of their method: "Biopsy by aspiration has,
we feel, few, if any, disadvantages to the patient from
the surgical standpoint. The interpretation of the histo-
logical picture (especially of the smears) requires both
an experienced and sympathetic pathologist. Undoubt-
edly, larger specimens uniformly fixed and stained
offer more satisfactory material upon which to render
a definite opinion, but such a preparation can too often
be obtained only at considerable disadvantage to the
patient or too late to be of any particular value in out-
lining treatment ... We do not advocate this method of
biopsy in any case where larger specimens of tissue
can be readily and safely secured by any other
In 1930, Ferguson [30] started to apply the tech-
nique developed by Martin and Ellis in the study of
prostate lesions from cytological specimens obtained
with a perineal puncture technique. He noted that a
positive diagnosis of prostate cancer by needle biopsy
was reliable for an experienced pathologist.
A year later, Ernst Mannheim, a German patholo-
gist, published a report entitled "Die Bedeutung der
Tumorpunktion für die Tumordiagnose" ("The signifi-
cance of tumor punctures for tumor diagnosis").
Mannheim's article should be considered the first report
on the technique of fine needle aspiration biopsy (i.a.,
featuring a needle with diameter of 1 mm). [31]
Mannheim, who was aware of the work of Martin and
Ellis, wanted to avoid disease dispersion and to cause
less harm to his patients. He characteristically noted in
his paper (translated in English): "Another extensive
report on our subject was published by Martin and
Ellis. I noticed it only when I had already started my
own investigations. However, these authors use a
strong trocar, making an incision into the skin above
the tumor prior to the puncture. Through aspiration
they obtain so much tumor substance that they were
able to embed and section small particels of tumor tis-
sues. But this kind of punching is a rather heroic inter-
vention affecting a considerable trauma; the risk of
promoting growth and metastazation of tumors is by no
means negligible" [31]. Worried about damage caused
by the procedure, he considered examining less cellular
material and proposed the use of a fine needle.
Mannheim reported his findings in 43 cases, mostly
breast cancer and neoplasms of the upper gastrointesti-
nal system. He led the European school of fine needle
aspiration biopsy, which completely modified the
approach to this method of diagnosis. According to
Koss, [28] Mannheim should be considered beyond any
doubt as the "spiritual leader of the European school of
thin needle aspiration biopsy, which was completely
modified the approach to this method of diagnosis".
In 1933, Fred Waldford Stewart (1894-1991), who
would later succeed Dr. Ewing in 1939 as Head of the
Department of Pathology, reported the results of nee-
dle aspiration biopsy from 2,500 neoplasms [32]. His
hallmark paper on aspiration biopsies interpreted the
results of Martin, Ellis and Coley. Years later, accord-
ing to Koss and Lieberman, he wrote that he "got
damned by several people for writing it, without any
proof" [29]. Stewart's study supplied the theoretical
basis of fine needle aspiration biopsy by referring to
clinical and laboratory associations and suggesting a
comparative study of the material using the new tech-
nique as well as conventional histological prepara-
tions. He also referred to the limitations and potential
errors of his technique and made mention not only of
the cytomorphological characteristics, but also of the
characteristics of the "architecture" of the aspired
material. Although he favoured aspiration biopsies, he
did mention the difficulties in fibrous alterations caus-
ing scanty aspirates and smears nearly void of any
cells. He also discussed the problems involved in the
diagnosis of sarcomas or various diseases of the thy-
roid gland and of the breast [32, 33].
In 1934, Martin and Ellis reported their experience
with 1,405 diagnoses of cancer in 662 lymph nodes,
280 breasts, 140 bones, 41 lung tumors and
182 miscellaneous lesions [27].
Martin and Ellis also considered the use of Ste-
wart's technique in clinical practice, especially for the
study of inoperable neoplastic tissues located in inac-
cessible parts of human body [33,34]. According to
A brief history of the technique of fine-needle aspiration
©Polish Histochemical et Cytochemical Society
Folia Histochem Cytobiol. 2009:47(2):
doi: 10.2478/v10042-009-0027-x
Page 3
A. Diamantis et al.
©Polish Histochemical et Cytochemical Society
Folia Histochem Cytobiol. 2009:47(2): 194 (191-197)
doi: 10.2478/v10042-009-0027-x
Table 1. Chronology of the events in the history of the use of needle in diagnosis and treatment
Page 4
Martin and Ellis, one of the advantages of needle biop-
sy over conventional surgical approaches for the histo-
logical diagnosis of tumors is the avoidance of cancer-
ous cell dispersion. Other studies further supported
this advantage [34].
Martin and Stewart collaborated on a 1936 report
on the indications, advantages and limitations of nee-
dle biopsy [34]. Reading their paper, one can under-
stand that Martin's influence was stronger, leading to
the overall conclusion in favor of aspiration biopsy
which downplayed Stewart's earlier reservations.
Grunze and Spriggs conduct a short comparison
between the work of Dudgeon's and Martin's teams
[35]. Dudgeon's team never worked on material from
aspiration biopsy and never performed any punctures
for diagnostic purposes. On the contrary, they were
primarily focused on the development of cytological
techniques, such as the imprint and wet film technique,
which were also used later in combination with fine
needle aspiration biopsy [22,23]. Dudgeon's wet film
technique secured a better preservation of cellular
material, but Martin, Ellis and Stewart developed the
true technique of needle biopsy. The latter team's work
was mostly associated with histological diagnosis
since they were more interested in the acquisition of
tissue than cellular material [26]. Both Dudgeon and
Patrick [22] and Martin and Ellis [26] used histologi-
cal staining protocols (varieties of hematoxylin-eosin
staining) that were not appropriate for the study of the
cytoplasm. Dudgeon and Patrick used haemalum and
eosin as counterstain, whereas Martin and Ellis used
haematoxylin and eosin.
In conclusion, the first report on needle biopsy dates
back to the 11
century, in the texts of the Arab doctor
Abulcasis. However, the 20
century should be con-
sidered the most crucial period in the history of FNA.
Dudgeon was the first to establish aspiration biopsy on
A brief history of the technique of fine-needle aspiration
©Polish Histochemical et Cytochemical Society
Folia Histochem Cytobiol. 2009:47(2):
doi: 10.2478/v10042-009-0027-x
Table 1. (continued)
Page 5
a scientific basis, while Martin and Ellis applied nee-
dle biopsies on a wide range of samples and clinical
cases. But, the first report on the use of fine, 22-gauge
needle should be attributed to Manheim. The elabora-
tion of FNA by the Swedish school in the forthcoming
years was crucial for the establishment of the tech-
nique and its world-wide acceptance.
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Submitted: 15 November, 2008
Accepted after review: 15 December, 2008
A brief history of the technique of fine-needle aspiration
©Polish Histochemical et Cytochemical Society
Folia Histochem Cytobiol. 2009:47(2):
doi: 10.2478/v10042-009-0027-x
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    • "Clinicians have used tissue biopsies for clinical decision-making since the 11 th century (Diamantis et al., 2009 ). The contribution of pathology analysis to clinical practice mostly relied on morphological information , being the gold standard for diagnosis in most diseases , particularly in cancer. "
    [Show abstract] [Hide abstract] ABSTRACT: Liver cancer has become the second cause of cancer-related death worldwide. Most patients are still diagnosed at intermediate or advanced stage, where potentially curative treatment options are not recommended. Unlike other solid tumors, there are no validated oncogenic addiction loops and the only systemic agent to improve survival in advanced disease is sorafenib. All phase 3 clinical trials testing molecular therapies after sorafenib have been negative, none of which selected patients based on predictive biomarkers of response. Theoretically, analysis of circulating cancer byproducts (e.g., circulating tumor cells, cell-free nucleic acids), namely "liquid biopsy," could provide easy access to molecular tumor information, improve patients' stratification and allow to assess tumor dynamics over time. Recent technical developments and preliminary data from other malignancies indicate that liquid biopsy might have a role in the future management of cancer patients.
    Full-text · Article · Apr 2015 · Discovery medicine
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    • "Especially, tissue biopsy by extracting suspicious lesions from the human body with a thin and hollow needle has been performed for disease diagnosis [6, 22]. Typically, ultrasound (US) and computed tomography (CT) imaging techniques have been commonly used to assess and guide the position of the needle with respect to the target tissue during the biopsy process [23, 24] . However, these methods can provide only limited resolution and accuracy of cancerous tissue detection. "
    [Show abstract] [Hide abstract] ABSTRACT: Direct metal patterning methods, such as screen printing, inkjet printing and gravure/flexography printing, are widely used to form electrodes or interconnections for printed electronic devices due to their inexpensive, simple and rapid fabrication as compared to vacuum-based conventional metallization processes. Here, we present direct metal patterning by modified screen printing on the curved surface of needle-type rod structures (i.e. rods with radius of ρ µm on the surface of the rod. Also, four pairs of line patterns were printed on the single rod for electrical interconnection. Printed patterns on the surface of the rod were used as electrodes for the control of a light emission diode (LED) as well as the real-time electrochemical impedance spectroscopy of electrolyte solutions and solid objects by the rod insertion. Furthermore, needles with multiple pairs of microelectrodes were used to measure the electrical impedance of biological samples such as fat and muscle tissues of porcine meat. In addition, a needle-type probe sensor with gas sensing capability was demonstrated by using a needle with printed Ag electrodes and Pd thin films.
    Preview · Article · Jan 2015 · Journal of Micromechanics and Microengineering
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    • "Fine needle aspiration cytology or biopsy (FNAC/FNAB) is a well-established diagnostic method used in many countries as a first-line diagnostic procedure aiding preoperative management of various palpable and non-palpable lesions. The history of needle biopsy spans several centuries; however, its use as a routine diagnostic technique was established mostly during the twentieth century [1]. It is increasingly being introduced into everyday clinical practice also in our region (Mures County, Romania). "
    [Show abstract] [Hide abstract] ABSTRACT: BackgroundFine needle aspiration (FNA) cytology is a well-established diagnostic method based on the microscopic interpretation of often scant cytological material; therefore, experience, good technique and smear quality are equally important in obtaining satisfactory results.Aims of StudyWe studied the use of fresh surgical pathology specimens for making so-called mock-FNA smears with the potential of cytohistological correlation. Additionally, we studied how this process aids the improvement of preparation technique and smear quality.MethodsCytological aspirates from 32 fresh biopsy specimens from various sites: lung (20), lymph nodes (6), and breast (6) were obtained, all with a clinical diagnosis of tumor. Aspiration was performed from grossly palpable tumors. 25G needle and Cameco-type syringe holder was used with minimal or no suction.ResultsUnfixed surgical specimens provided sufficient cytological material that resulted in good quality smears. After standard processing of specimens into microscopic sections from paraffin embedded tissues, cytohistological case-series were created. No significant alteration was reported in tissue architecture on hematoxylin-eosin stained sections after the aspiration procedure. A gradual, but steady improvement was observed in smear quality just after a few preparations.Discussions and ConclusionsOur study proved that surgical specimens may be used as a source of cytological material to create cytohistological correlation studies and also to improve FNA cytology skills. The use of very fine gauge needle (25G, 0,6 mm diameter) during the sampling process does not alter tissue architecture therefore the final histopathological diagnosis is not compromised. We conclude that by using fresh surgical specimens useful cytohistological collections can be created both as a teaching resource and as improving experience.
    Full-text · Article · Aug 2014 · PLoS ONE
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