an Istanbul breeze

İSTANBUL

İZMİT, KOCAELİ

NADİR PAKSOY, MD, MIACProfessor of Pathology & Cytopathologist, Kocaeli University – TURKEY

A voyage through the past pages of cyto-pathology

TOPIC 1; STORY OF HEMATOXYLIN

Hematoxylin (HE) is a key stain in pathology and cytology.

Origin of HE is a tree, called logwood in English and Haematoxylum in Latin; which means “bloodwood” (“haima”being Greek for blood and “xulon” for wood).

HE Tree is native tree to southern Mexico and Central America.HE tree was used for a long time as natural source of textile dye for Mayas and Aztecs.

Dye is extracted from the chips of the woodIt’s called ‘tree with blood colored wood’.

By the late 1500, European textile industry recognized the value of the tree as natural source of textile dye. Then the importance of the tree suddenly increased and even caused war between Spanish and English ships.

Around 1865, German scientist Boehmer who was inspired by the use of HEMATOXYLIN in textile industry had used it in combination with mordant (chemical procedure to increase dyeing effect), and published its usage in histology.

Hematoxylin gained its popularity in the late 1800’s.Eosin is a synthetic analine dye, and combination of H. with eosin was first proposed in 1871 by Poole.Since then H&E has been an indispensable stain for us.

Here comes the first question!

Today, one country in the American continent is using Hematoxylin tree as a symbol on her national flag. Which one of the following countries is this?

a) Mexicob) Brazilc) Belize (British Honduras) d) Panama

The correct answer is “C – Belize (British Honduras)”.

The British logwood cutters (baymen) found a river mouth with dense jungle containing hematoxylin trees; settled and formed a colony (British Honduras) in mid 1600’s. This is how hematoxylin tree caused the emergence of a new country (Belize).

H. tree; a black and a white cutter are the national amblem of Belize.

TOPIC 2; TROY AND THE PATHOLOGIST

TROY is an ancient city in Turkey, known as the center of many civilizations.TROY is located in south of the strait of the DARDANELLES (called Canakkale in Turkish).

The history of Troy dates back to 3000 B.C. Trojan war was described in the Greek Epic Iliad by Homer.Troy, the film, (2004) with starring Brad Pitt created worldwide publicity and revoked the interest to Troy again.

German businessman and archeologist Schliemann began excavating the Troy area in two different campaigns at 1868 and again after 1878.Schliemann’s excavation revealed some ancient cities. Meanwhile he and his wife claimed that they have already found the Troy’s LOST TREASURE (Priam’s treasure) in 1873.

They smuggled the treasure to Berlin and donated to German people. The treasure was also on display for a time in Pergamon Museum. After the WW II Russians took the treasure to Moscow. Today, it is kept in the Pushkin Museum in Moscow. However some artifacts are kept at the Istanbul Archeology Museum as well as at the Neues Museum in Berlin.

Later Schliemann traded some treasures to the government of Turkish Empire (Ottoman Empire) in exchange for permission to dig at Troy again in 1878.

Here comes the question 2!

A well known pathologist joined Schliemann’s second campaign of Troy excavations as a site/camp doctor. Do you know who this pathologist was?

a) Carl Rokitanskyb) Paul Langerhansc) Lauren Ackermand) Rudolph Virchowe) Gustav Giemsa

The correct answer is “D – Rudolph Virchow (1821-1905)”

German pathologist, considered as the founder of cellular pathology was also a anthropologist, prehistorian and politician (political antagonist of Bismarck).He was credited with the interest of social medicine and public health.

TOPIC 3; ALMOST THE NEAR DEATH BIOPSY AND SURGICAL PATHOLOGY

Towards the end of 19th century, the notion that microscopic examination of tissues from living patients has just began at the European medical community.

Large numbers of doctors were against biopsy because, for them, a diagnosis of malignancy can only be obtained from the autopsy.Between the pro/anti discussions on the use of biopsy an unfortunate event happened. This was nearly a death sentence for biopsy & microscopic diagnosis of malignancy.

Carl Rokitansky (1804 – 1878): Bohemian (Czech/Austria) Pathologist. Perfomed 30.000 autopsies during his career.

Let’s have a look at this unfortunate event for pathologists.

In Germany the newly appointed 55 years old Emperor Frederick III developed a throat lesion in 1887. German doctors clinically diagnosed as laryngeal carcinoma.

Emperor’s wife was a daughter of Queen Victoria of the United Kingdom. Probably because of this connection, the eminent British otolaryngologist Dr Morell McKenzie came to Berlin and biopsied the laryngeal lesion.

Here comes the question3!This was one of the first uses of biopsy technique; since microscopical evaluation of tissue from living patients in those years had been largely unheard of. The pathologist interpreted the biopsy as benign. Who was the pathologist?

a) Paul Langerhans

b) Carl Rokitansky

c) Ludwig Aschoff

d) Rudolf Virchow

The correct answer is “D – Rudolf Virchow (1821-1905)”

Despite Virchow’s “benign” diagnosis the Emperor’s condition became worse. Within a few months the Emperor died from laryngeal carcinoma.

The consequences of the discrepancy in diagnosis caused shock waves in the medical community in Germany and Britain.

From the detailed description of the actual biopsies published by Vircow himself in British Medical Journal (1887), removed tissue may well have been free from malignancy. Unfortunately, blocks and slides are no longer available.(Underwood: Introduction to Biopsy Interpretation/Surgical Pathology. Springer Verlag, 1981)

Both McKenzie and Virchow were blamed. Virchow remained largely unaffected but McKenzie received many professional attacks, he was expelled from Royal College of Physicians. His reputation collapsed. From the point of pathology, this unfortunate event reinforced the opinion of the anti-biopsy opponents that biopsy for diagnosing cancer was not a reliable method.

TOPIC 4; PRESIDENT & PATHOLOGIST

Virchow was an eminent pathologist and politician as well but never became a president of the state. However in the recent history of politics, there was a head of state who was also a medical doctor and pathologist.

Do you have any idea who this president was?a) Salvador Allende – Chile

b) Javier Arias Stella – Peru

c) Ernesto Che Guevara – Cuba

d) Besar Esad – Syria

Here comes the question 4!

The correct answer is A – Salvador Allende, Chilean president in 1970-1973 was a pathologist.

He is known as the first Marxist president to gain power in a free democratic election.

On 11th September 1973, a military coup removed Allende’s government from power. Allende died in the fighting in the presidential palace in Santiago, the capital city of Chile. (Possibly committed suicide). General Pinochet’s military dictatorship governed Chile until 1990.Virchow’s followers established pathology depertmant in Latin America and initiated Cources in Social medicine Allende’s experiences as a doctor,pathologist and politician were shaped under such educational model. (B.Friedmann. Salvador Allende: Pathologist, Populist, and President. Lab Soft News, March22,2006).

TOPIC 5; NOBEL PRIZE & PATHOLOGISTS

First Nobel Prize winner (Laureate) in Medicine is Behring in 1901 for discovering diphtheria vaccine.Since 1901 until 2010, in 109 years almost 100 winners received Nobel Prize in Medicine. (WW I, WW II no prize was given)

Nobel prizes are awarded for outstanding contribution in Physiology or Medicine by Swedish Academy since 1901.

Among more than 100 Nobel winners in medicine were there any pathologists?

a) Yes

b) No

Here comes the question 5!

The correct answer is “A” There were 3 pathologists who won the Prize:

• 1906 Ramon Cajal (Spain), • 1934 George Whipple (USA),• 2005 Robin Warren (Australia).

2005 Robin Warren (Australian Pathologist 1937-)

Nobel Laureate who is credited with the be discovery of the bacterium Helicobacter Pylori (1979), together with Barry Marshall (microbiologist). Warren proved that HP is the cause of stomach ulcers and helped develop urea breath-test for detecting HP in ulcer patients.

1934 George Whipple (1878 – 1976) American pathologist.

Duodenal bx: Whipple’s disease; foamy macrophages

Whipple won the Nobel Prize with 2 other non-pathologist doctors “for their discoveries concerning liver therapy in cases of anemia” Whipple’s main research was concern with anemia and pathology of liver which led to liver treatment of “pernicious anemia”.

He also described Whipple’s disease (malabsorption + weight loss + diarrhea + joint pain). He is not related to surgeon Allen Whipple who described the Whipple procedure. The two were life long friends.

1906 Ramon Cajal (1852 – 1934) Spanish pathologist, neuroscientist,

Nobel laureate together with Italian histologist Camillo Golgi (1843 - 1926) “in recognition of their work on the structure of the nervous system”.

TOPIC 6; SOME “FIRSTS” IN CYTOLOGY

From Dr. JC Prolla, Brazil

The usefulness of fine needle aspiration is today widely accepted.Do you have any idea who first applied FNA?

a) Franzen – Zajicekb) Hajduc) Frabled) Paget

Here comes the question 6!

The correct answer is “D – Paget”

British surgeon Sir James Paget (1814 – 1879 ) applied the first recorded FNA in 1853.He prepared smears from needle aspirate of a breast carcinoma [Paget J. Lectures on surgical pathology Langman, Lerden, 1853].

In this context, I would like to mention a few other “firsts” in cytology. First Imprint Cytology:

Johannes Müller (1801 – 1853) German pathologist in Berlin, made smears from tumors in 1838. Müller showed cancer cells in the microscope on scrapings from the cut surface of surgically excised tumors.

First FNA in USA

breast FNA one of the first in USA (from: Rosai and Ackerman)

James Ewing (1866 – 1943), pathologist working at the Memorial Hospital for Cancer in New York, introduced aspiration cytology in USA in 1920’s.

First pioneers of FNA in Europe, Swedish hematologist and pathologists (Zajicek, Franzen and Lowhagen) pioneered for widespread use of FNA. With their efforts FNA began to recieve international attention in 1980’s.

Franzen

2008

Here comes another question on this topic: Question 7!

Who is the first cytopathologist described koilocytotic atypia?

a) Dr. Papanicolaou b) Dr. Leopold Koss c) Dr. Bernard Naylord) Dr. George Wied

The correct answer is “B – Dr. Leopold Koss”

The term of koilocytotic atypia was first introduced by Leopold Koss in 1956 (two decades later, association between HPV and koilocytosis was first reported by Meissels & Purola).

TOPIC 7; DR PAP

Needless to say we all know about the Pap test and its inventor Dr. Papanicolaou.

What is the speciality of Dr Papanicolaou?

a) Pathologistb) Gynecologistc) Microbiologistd) Anatomy

Here comes the question 8!

The correct answer is “D – Dr. Papanicolaou” was an anatomist.

Papanicolaou studied medicine at the University of Athens in Greece (1904); emigrated to the U.S. in order to work in the Depertmant of Anatomy at the Cornell University.Dr. Papanicolaou worked examining vaginal smears of guinea pigs to determine the existence of a menstrual cycle. Dr. Papanicolaou observed the changes in the female genital tract of a guinea pig.

Eventually, Dr. Papanicolaou became interested in the menstrual cycle of women. While examining smears he noticed some abnormal cells in which he thought that they could be related to cervical cancer. This is how the cervical smear began.He first reported that uterine cancer could be diagnosed by means of a vaginal smear in 1928, but the importance of his work was not recognized until the publication, together with Herbert Traut, of Diagnosis of Uterine Cancer by the Vaginal Smear in 1943.

Paper by Pap in 1928 Battle Creek, Mich. USA

Monographed by Pap and Traut in 1943(From Dr. B. Naylor)

THE 8th AND LAST TOPIC; UNKNOWN SCIENTIST

• There was another medical scientist who described abnormal cells in cervical smears almost at the same time with Papanicolaou.

• Although Dr. Pap is credited for cervical

smear; this scientist is not widely known.

Do you know the name and the nationality of this unfortunate pathologist?

a) Dr Behçet – Turkey

b) Dr Babeş – Romaniac) Dr Ross – UK

d) Dr Bilharza – Germany

Here comes the question 9!

The correct answer is “B – Dr Aurel Babeş (1886-1962)”

Romanian Scientist. He reported the diagnosis of uterine cancer by the use of cervical smear in 1927 and 1928.

His method of cancer diagnosis was first published in a Romanian Congress in 1927 and later in a French Medical Journal in 1928, same year with Dr. Pap’s first report.Dr. Babeş did not publish any article on this subject. However, Romania refers to cervical smear test as “ method Babeş – Papanicolaou” in honor of Dr. Babeş.

1927 BUCHAREST, ROMANIA

1928 PARIS,FRANCE

(From Dr. B. Naylor)

Other doctors in this question are:

Dr. Theodor Bilharza: pathologist worked in Egypt discovered the trematod worm is the cause of urinary schistosomiasis (1851).

Dr. Ronald Ross: discovered malaria was transmitted by mosquitos (1902).

Dr. Hulusi Behçet: Turkish physician, dermatologist described Behçet Disease (1937).

Main References1. Bernard Naylor. The century for

cytopathology. Acta Cytologica 44 (5): 709-725, 2000.

2. Anthony A. Gal. In search of the origins of modern surgical pathology. Advances in Anatomic Pathology 8(1): 1-13, 2001.

3. Cristian Smith. The history of Hematoxyline. Medical Lab Observer 38(5): 18, 20-22, 2006.

4. Steven Hajdu and Hormoz Ehya. Foundation of diagnostic cytology. Annals of Lab Med. 38(3): 296-299,2008.

I hope you enjoyed this short trip through the pages of the history of cytopathology.Have a safe journey back home and remember Istanbul with good memories. Thanks again

Prof.Dr. Nadir PAKSOY(citographica@superonline.com)