malignant tumors of the thymus gland -...

MALIGNANT TUMORS OF T H E THYMUS GLAND

EDWARD H. CROSBY, M.D.'

(Prom the Department of Path~logy oj Albany Medical College and the Pathological Lab- oratorg oj Albany Hospital, Albany, N . Y.)

Malignant tumors of the thymus are of interest not only on account of their infrequency but also because of the controversy regarding the histogenesis of the gland. Thymic tumors, which are distinguishable a t post-mortem examination from tumors of the mediastinal lymph nodes or of the lung, usually surround and compress the trachea, bronchi, pericardium, and great vessels. By compression, and less often by invasion of the vessels and passages, they cause death by asphyxia and venous obstruction, which may develop gradually or very suddenly.

The points indicating the thymic origin of mediastinal sar- comata are summed up by Jones (1) as follows:

1. The situation of a large, slightly lobulated tumor a t the site of the thymus.

2. The extension of this tumor downward behind the sternum without infiltration of the bone.

3. The involvement of the pericartlium and of the pleura by direct lymphatic extension.

4. The resemblance to thymic tissue on histological exnmin a t' ion.

I n connection with the last point some authors insist that all the histological elements of the thymus be found in some form, but a resemblance of the chief cell type to the thymic lymphocyte and the presence of Hassall's corpuscles in some parts of the tumor a t least would seem adequate.

Ewing (2) gives a classification of thymic tumors which has been widely quoted. His main groups are as follows:

1. 1,ymphosarcoma or thymoma, composed of a diffuse growth of round, polyhedral, and giant cells.

2. Carcinoma arising in the reticulum cells. 3. Spindle-cell sarcorria or myxosarcoma, very rare and somewhat ques-

tionably attributed t,o the stroma.

The third and first groups are still under dispute because of the This study was made while the author ~ 2 x 8 Eugene Littauer Research Fellow in

Pathology in Albany Medical College. 461

462 EDWARD H. CROSBY

questionable mesoblastic origin of the small round cell of the thymus. This point will be discussed later.

Harris (3) in 1892, An~brosirii (4) in 1894, and later Jories ( I ) , Janeway ( 5 ) , and others discussed the clinical symptoms of thymic tumors. The first symptonl is usually cough or hoarseness without expectoration or hemoptysis. This leads to the subjective symp- tom of suffocation without physical signs in the chest or visible cause of obstruction in the upper passages. Puffiness about the eyelids and fullness about the neck, toget,her with :L pecu1i:tr pink disco1or:ttion of the eyelids, :ls described hy ('rnver ((i), may 1)e ~)rescnt early in thc course of the disease. Engorgement of the veins of the neck, cyanosis, edema of the face and upper extrcniities, :t feeling of oppression in the chest, palpitj:ttion, and pain beneitth the sternum, which is constrictive and well localized, soon follow and rapidly become more marked. Alteration of the voice, head- ache, dysphagia, and gradually increztsing emaciation :Ire associated with the appearance of a tumor growth in the axilla or in the ccrvi- c:tl region. As the disease progresses, dyspnett becomes extrcrnc, inequality of the pulse is noticeable, hydrothorax develops, ancl the heart becomes displaced. The most common con~plications of thymic tumors are pleurisy with effusion, pericjtrditis with effusion, obliteration of the vessels in the neck, arid obstruction of the esophagus and trachea.

,J:~neway ( 5 ) has urged the import:tnce of early diagnosis :tnd familiarity with the clinical course of these tu~nors, for in :L lnrgc number of cascs rt~dium or x-ray therapy offers relief, even if not a prospect of cure. However, the result of tre:tt,ment depends not only upon the early diagnosis and institutio~l of trentinerlt but also upon the histogenesis of the tumor.

Roentgen examination is of the utmost diagnostic importance. The location and the appearance of the shadow :ire characteristic. The shadow is immediately above the pericardium :tnd higher th:tn the usual location of enlarged peribronchial lymph glands.

A circular, sharply defined, flattened, non-pu1s:~ting mass in the anterior wall of the thorax, in the absence of other evidence to the contrary, justifies a tentative diagnosis of thy mom:^. Pool (7) in 1925, Dwyer (8) in 1927, and Doub (9) in 1930 reported cases in which a diagnosis of probable thymoma was made by x-ray. The tumor w:~s subjected to deep x-ray therapy and some of the patients showed great irnprovemerit in their symptoms. In 1925 Grover, Christie, Merritt, and Coe (10) reported two similar cases. Both

MALIGNANT TUMORS OF THYMUS GLAND 463

patients were treated with deep x-ray therapy, and the authors state that the results were very encouraging.

The term " thymoma" was first introduced by Grandhomme (11) in 1900. At that time it was applied to all malignant tumors arising in the thymus gland. Brown (12), in discussing the term, states that i t should be used only to indicate primary carcinoma, which he considers the only real thymic tumor. Crotti (13), however, believes that this term has the advantage of being accurate whether the cells are derived from endoderm or mesoderm, and that it also clearly associates the tumor with its place of origin. Bell (14), in describing tumors of the thymus associated with myasthenia gravis, uses the term "thymoma" to include non- malignant tumors, and Margolis (15) apparently agrees with Bell. Strauss (16) believes that those growths of the thymus composed of small round cells like those of the cortex should be called thymoma, those characterized by a rich connective-tissue stroma and showing the presence of spindle cells be called sarcoma, and those growths derived from epithelial cells of Hassall's corpuscles be diagnosed carcinoma. Evert (17) uses the term sarcomatous thymoma because these tumors do not resemble true lymphosarcoma morphologically, and because he regards the term as equally applicable whether the parenchyma is of epithelial or of lymphoid origin. The consensus is that the term "thymoma" should be used to designate any malignant tumor primary in the thymus.

To understand the nature of the neoplastic diseases of the thymus, it is necessary to review briefly the embryology and the histology of the thymus gland. I t is generally believed that the thymus originates from the endodermal epithelium of the third branchial clefts as a paired organ. At about the second month of prenatal life (Hammar, 18), the thymus, which up to this time has been an endodermal organ, begins to be infiltrated with lympho- cytes. These cells migrate into, proliferate among, and separate the epithelial cells of the thymus (Maximow, 19). Danchakoff (20) showed that the thymus cell is a true small lymphocyte and that it may differentiate into granular lymphatic cells or into plasma cells. This differentiation was brought about by treating animals with x-ray. Although most authors agree with this dual interpretation (Badertscher, 21; Danchakoff, 20; Hammar, 18; Brannan, 22; Schaffer, 23; Crotti, 13; Stengel and Fox, 24; Voges, 25), other observers believe that the endodermal cells (endodermal thymic reticulum) differentiate to form the so-called thymic cells.


They are of the monist school, which is headed by Ewing (2)) Stohr (26)) and Prenant (27). In 1910 Pappenheimer (28) was also of the monist school, but his views as set forth in his later work have changed so that he may now be termed a dualist. Bell (14) has described transition forms between the reticulum cells and the thymic cells. The origin of the thymic cell is thus still a matter in dispute and, until this dispute is settled, definite classification of thymic tumors is impossible.

Schaffer (23) describes the epithelial portions of the thymus gland as follows: "Within the medulla, but never in the cortex, are found peculiar concentrically laminated bodies called the concentric corpuscles of Hassall. These are nests of flattened epitheli~tl cells arranged concentrically around one or more central cells, these last having often undergone a degenerative process. Some- times the corpuscles are compound, two or three being grouped together and similarly enclosed by flattened cells." By trans- planting the thymus of young guinea-pigs, Jordan and Horsley (29), quoting the work of Jaff6 and Plavska to support their theories, showed that the concentric corpuscles of Hassall could not be interpreted as remnants of endodermal ducts, as had previously been supposed. Regenerating transplants are said to form new corpuscles by a process of hypertrophy and aggregation of reticulum cells. This agrees with the earlier claims of Hammnr (18). Jordan and Horsley (29) believe that the concentric corpuscles arise chiefly from hypertrophied endothelial cells of precapillary arterioles and the immediately investing reticulum cells. If Hassall's corpuscles actually represent in part remnants of atrophic capillaries and precapillaries, then similar structures should appear in other lymphoid organs. Structures resembling Hassall's corpuscles were found by Jordan and Horsley in atrophic subcutaneous lymph nodes of the rabbit. It is now generally ac- cepted that Hassall's corpuscles are endodermal in origin.

D. B., a young Italian laborer, twenty-two years of age, single, one year in this country, was perfectly well until Aug. 15, 1923, when a mild cough developed, which increased in severity and was associated with discomfort in the upper median portion of the chest. On Oct. 1, 1923, he was unable to go to work because of the severity of the coughing spells, pain in the chest, dyspnea, and cyanosis, associated with distention of the

This case has been briefly reported by Hosoi and Stewart in their article on "Dif- ferential Diagnoeis of Mediastinal Tumors," Arch. Int. Med., 47: 230, 1931.


veins of the neck. He was admitted to the medical service of the Albany Hospital on Oct. 12, 1923, a t which time the symptoms had increased in severity following several severe attacks of choking and dyspnea. These attacks came on when he attempted to swallow food, and were so severe

FIG. 1. ANTERO-POBTERIOR VIEW OF MEDIARTINAL TUMOR WHICH HAS BEEN SEC- TIONED, EXPORINQ THE PERICARDIAL CAVITY

The heart has been removed. The trachea forms part of the V-shaped notch in the upper part. The lobulations and general shape of the tumor suggest a thymic origin.

that i t was believed that particles of food had entered and obstructed the larynx. At first these attacks lasted only a few seconds. The third attack, and the one which brought the patient to the hospital, could not be relieved.

The patient's past history and the family history were irrelevant. Physical examination showed a well developed boy suffering from

466 EDWARD 11. ( 7 ~ ~ ~ ~ ~

extreme dyspnea ant1 rnarkcd cyanosis. He was perspirir~g freely, and, not being able to speak English, pointed to his thro:it and the upper part, of his chest. The left hand and arm were swollen and the pulse was weaker in the left radi:tl artery than in the right. The pharynx was somewhat reddened and showed two small patches of exudate, but the larynx was free from membrane or obstruction. The heart borders were not enlarged to percussion, and the heart sounds were normal. There were dullness and diminished breath sounds in Ihe upper left chest posteriorly and on both sides of the sternum in front. There were coarse r8les over both bases. The white blood count was 23,000, temperature 99' F., respiration 28 per minute, and pulse 120 per minute.

The respiratory difficulty increased, the veins of the neck bec:tme prominent, and the cyanosis remained marked. An intubation w:ts attempted, but the patient was not relieved, and he diet1 three hours after ttdrni7sion to the hospital.

Necropsy was performed four hours post rnortern by Dr. I ' ic to~ C. Jacobsen.

The post-mortem examination was limited to an examination of the chest cavity, the thoracic organs being removed in toto. The striking feature was n large, dark red, nodular mass present in the mediastinurn and apparently enveloping all other structures. The he:~rt was entirely hidden until the lower portion of the mass w:is raised. The peric:lrtli:11 sac was fluctuant and bulging.

The mediastinal tumor measured 30 x 13 x 12 cm. and weighed 1975 gm. Its exposed surfaces were covered by a thin connective-tissue capsule, uniformly very dark red in color, with the smoothness of the surface interrupted by numerous lobulations. The tissue was moderately firm and resilient. A longitudinal section was made through the center of thr mass, uhich was roughly triangular in outline with the apex in- ferior. The heart was practict~lly embedded in the new growth. The sectioncd surface had a cellular ; ~ n d meaty appearance. This m:tss was subdivided above into lobes, which were tan colored and which in turn were subdivided by fine red lines into lobules whose arrangement bore a striking resemblance to sm:tll cerebral convolutions. The remainder of the tissues presented for the most part :in homogeneous dark red surface siniilar to the external surface.

The lungs had been greatly compressed and were collapsed. By palpation, indurated areas could be detected in the lower lobe of the right lung. The indurated tissue directly beneath the pleura was dull white and opaque.

The pericardial sac was opened, allowing the escape of about 200 C.C. of opaclue, viscid, red fluid. The epict~rdium was thickened and opaque. The pericardium was di~colored deep red, and was :idherent to the heart in places by a thin layer of fibrinous rnaterial over these retltlene(l r e Dissection of the heart showed norrn:tl endocardium and valves. The myocardium was a little pale and as it :tpproached the epicnrdiurn the Iwo tissues blended imperceptibly

Irregular patches of tissue of an :ippetlrancc and consistency similar

Fro. 3. TUMOR CELLS AROUND A BLOOD VESSEL IN THE LUNG

467


to the mediastinal tumor were distributed irregularly over the pleural surfaces of the diaphragm, chiefly on the right side.

The trachea and the esophagus were greatly flattened, antero-posteriorly. The aorta was hypoplastic.

Microscopic Examination: The tumor was composed quite uniformly of densely packed cells with very little stroma. The cells in general were of the small lymphocyte type with variation to the 1:~rge lymphocyte. The nuclei were large, occupying almost the entire cell, :tnd mitotic figures were numerous. Sections stained by Goodpasture's method revealed no oxidase granules. I n one section, several bodies were found which re- sembled Hassall's corpuscles with degenerative changes. The tumor was vaguely subdivided into lobules by fibro-vascular septa from which a reticulum-like stroma ramified a brief distance between the tumor cells. This reticulum was well dernonstrated by Foot's silver stain. The capsule of the tumor was invaded and the lymph vessels wherever present contained a few or many lymphoid cells. Small hemorrhages and areas of necrosis were present throughout the section.

The pericardium and the epicardium were infiltrated with tumor cells, which also invaded the myocardium in nearly its entire thickness. The epicardium, by influx of tumor cells, was fully three times its normal thickness. The cells were present in the lymph spaces but not in the blood vessels.

The lungs showed large masses of tumor throughout the sections. 12

perivascular infiltration was conspicuous. The alveoli adjacent to vessels were often filled with t,umor, and the tumor cells made their way between the capillary and the lining epithelium.

The diaphragmatic pleura was covered with a thick layer of turnor cells which had also infiltrated the muscle to a marked degree.

The anatomical diagnosis was malignant turnor of the thymus with metastasis to the pleura, the lungs, the diaphragm, and the myocardium, and compression of the trachea, the esophagus, and the aorta.

The tumor primary in the mediastinurn, because of its position, its lobulated structure, and the nature of the type cell which was encountered, without doubt arose in the thymus gland. Metastasis occurred to the lungs, the pericardium and pleura, the myocardium, and the diaphragm.

I n reviewing t h e subject of thymic neoplasms, confusion was encountered not only in regard t o t he anatomical diagnosis b u t also the nature of the growth a n d manner of metastasis. An a t t empt has been made t o classify the malignant tumors primary in the thymus gland which have been reported since Rubaschow (30), in 1911, reported a carcinoma primary i n the thymus together with 36 collected cases. I n 1896, Hoffmann (31) had reviewed 33 cases of malignant t umor primary i n the thymus gland, which with Rubaschow's collection make t h e total 69. Brannan (22), however, pointed ou t t h a t Vermorel and Thiroloix (32) published a

FIG. 5. TUMOR TISSUE STAINED BY THE FOOTE-MENARD METHOD, SHOW IN^ THE RELATION OF RETICULUM FIBERS TO THE NEOPLABTIC CELLS

First Series: Sarcoma of the Thymus (Thym.oma)

Case No. --

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Author

Cooper (33)

Powell (34)

Moore (35)

Harris (3): 9 cases were reported and it is believed t h a t t h e y were all primary in the thymus

I-Iarris

Harris

Harris

Harris

Harris

Harris

Acker (36)

Weigert and Laquer (37)

de la Camp (38)

Date

1832

1870

1884

1892

1892

1892

1892

1892

1892

1893

1892

1892

1896

1901

1903

Diagnosis

Medullary sarcoma of thymus

Thymic lymphocytoma

Round-cell sarcoma primary in thymus

Hound-cell sarcoma of anterior mediastinum

Itound-cell sarcoma of anterior medinstinurn

Sarcoma of anterior mediastinum

Round-cell sarcoma of anterior mediastinum

Itound-cell sarcoma of anterior mediastinum

Itound-cell sarcoma of anterior mediastinum

Primary lymphosarcoma of anterior mediastinum

Hound-cell sarcoma of anterior mediastinum

Primary sarcoma of anterior rnedi- astinum

Large round-cell sarcoma of thymus

Lymphosarcoma of thymus asso- ciat,ed with myasthenia gravis

Sarcoma of anterior mediastinum primary in persistent thy- mu8

Metastasis

Infiltration of the innominate vein

Infiltration of both lungs, both pleurae, pericardium, mediastirial and lumbar lymph glands

Not given

Both pleurae, right lung, mediastinal and supra- clavicularlyrnph glands

Right lung and mediastinal lymph glands

Right lung

Left lung, mediastinul and cervical lymph glands

Left lung, peric ar d' ~ u m , trachea, left bronchus, mediast inal lymph glands, pancreas, mesenteric lymph gland

Left lung, pericardium

Left lung, pericardium

Left lung

Left lung, left pleura. Left lung was diseased by tuberculosis

Both lungs, left axilla

Pericardium

Inf. bronchial, jugular, cervical, mediastinnl, retroperitoneal lymph glands, both lungs, liver

Case No. --

16

IT

18

19

20

21

22

23

24

25

26

27

28

29

First Series: Sarcoma of th

Zniniewicz

Grawitz (43)

Sheen (44)

Sheen

Symmers (45)

Agc

:12

32

33

17 (42)

Zniniewicz

Zniniewicz

Sex

--

I+'

M

F

M

Autlior

-

I'amasaki (:19)

lIun, l3lumer, :inti Streeter (40)

Orth (41)

Zniniewicz

Date

--

1904

1904

1910

1911

1911

1911

1911

1911

1 9 1 1 ?

1911

1911

l1h.?lrnus (Thymoma) (continued)

Barbano (46)

Ewing (2)

Ewing

1,yrnphosarcoma (?) of thymus

M

M

F

F

?

F

Lymphosarcoma of thymus associated with myasthenia gravis

Sarcoma of thymus

25

17

86

12

7 mos.

18

56

1912

1916

1916

Lymphoscircoma primary in thymus

I~ymphosarcoma primary in thymus

M

F

M

Lymphosarcoma of thymus

30

19

32



Sarcoma of thymus

Sarcomit of thymus

Ma1ign:~nt thymoma

Thymic lymphosarcoma (round- cell sarcoma)

Malignant thymoma resembling lymphosarcoma

Malignant thymoma

Mediastinal and gastric lymph nodes, right pleura, pericardium

M u s c l e s i n g e n e r a l showed evidence of metastasis

Both pleurae, both lungs, pericardium, bronchial a n d suprsclavicul :~r lymph nodes, left jugu- I:ir vein, liver, left ovary

Bothlungs, superior venu cava, pericardium, trachea, bronchial lymph glands, left kidney, left suprarenal, pancreas, and sternum

Both lungs, pericardium, cervical lymph glands, innominate vein, intercostal muscles, sternum, both kidneys, liver

Right pleura, pericnr- dium, cervical and mediastinal lymph glands, erosion through sternum and into intercostal muscles

Left pleura, left lung, left bronchus, pericardium, left humerus

Pericardium, myocardium

Both pleurae, both lungs, b r o n c h i a l l y m p h glands, spleen, liver

Cervical and bronchial lymph glands

Itight lobe of thyroid, trachea, liver

Glands of neck and in- guinal region, pericardium, mediastinal vessels

Pleura, axi l lary a n d bronchial lymph gland8

Cervical lymph nodes. Diagnosis was made by biopsy

Fr 30

31

3'2

33

34

35

36

37

38

39

40

41

42

43

(continzred)

Metnvtaaia

--

Spleen

ltight pleura, lcft peribronchial tissue, thoracic lymph nodes, pericardium, both ventricles

Cervical and retroperitoneal lymph glands, pericardium, left ventricle, both kidneys

?

Pleura, pericardium, myocardium, spleen, liver

Lymph glands of neck

Both lungs, both pleurae, mediastinsl : ~ n d axillury lymph nodes, perforation of sternurn, liver, apleen

Mediastinal and :~xillnry lymph glands

Mediastinal, cervical nb- dorninal lymph glands, lymphomatous spleen, liver, kidneys

ltight pleura, right lung, cervical, mediastinal, retroperitoneal lymph nodes, spleen, liver

Pleura, lungs, myocardium, diaphragm, liver

M e d i a s t i n a l l y m p h glarids

ltight lung, pericardiuni

110th pleurae, bothlungs, pericardium, myocardium, carotid, right diaphragm, mesenteric lymph glands, both oculomotor nerves, right eye, both kidneys, spleen, liver

First Series:

Author

Major (47)

Symmers (48)

Symmers

Brand (49)

Foot (50)

Gerlach (51)

Jancway (5)

Jtinewity

Janewey

Janewt~y

IIarvier (52)

Cleland(53)

Delessert (54)

Meigs and de Hchweinitz (55)

o j the

Age

-- --

?

26

17

28

9

34

4S

3'2

8

25

56

33

12

21

Thymus (Thymonza)

Diaanosia

-

Lymphosarcoma of thymus associated with acute lymphatic leukemia

Lymphosarcoma, of thymus

Lymphosarcoma of anterior mediastinum corre- sponding to region of thymus

Spindle-cell ear- coma of thymus

Malignant thy - moma


Small rountl-cell thymo~na

Giant-cell thymoma

Thymic lymphocytoma associated with lym- phat,ic leukemia

Large round-cell thymon~a (sarcoma)

Sarcoma of thymus

Thymoma (small round-cell sarcoma)

Lymphosarcoma of possible thymic origin

Round-cell sarcoma of the anterior mediastinum probably arising in the thymus

Date

-- 1918

1918

1918

1920

1920

1920

1!)20

19'20

1920

1920

1921

1922

1022

1894

Sarcoma

Sex

-- ?

M

M

M

M

E'

F

M

M

M

F

M

M

M

- Case No.

-.

44

Wollstein arid McLean (6")

Schmidt (63)

Noice (64)

First Series: Sarcoma of the Thymus (Thymoma) (continued)

Zanelli (65)

Young and Spalding (67)

Metastasis

Diaphragm, posterior wall of thorax. Post- mortem examination was not complete but it was believed that metastases resemt)led the previous case

Tracheal , bronchial lymph nodes, perforation of sternum, liver

Tracheal , bronchial lymph nodes, perforation of sternum, liver

Left pleura, both kidneys

Kidneys

Retroperitoneal lymph nodes, vena cava, both kidneys

Bronchial, left cervical lymph glands, liver, kidneys, skin

Left pleura, left lung, cervical and abdominal

Jones (1)

Diagnosis

Round-cell sarcoma of anterior m e d i a s t i n u m probably arising in the thymus

M:ilign:~nt t , l~y- rnoma

Lymphocytomaof thymus (lymphosarcoma)

Sarcoma of thymus

Small-cell lymphosarcoma of thymus

Malignant small- cell t h y moma associated with lymphatic leukemia


Lyrnphosarcoma of thymus

Lymphosarcoma of thymus asso- c i a t e d w i t h Hodgkin's dis- 8888

Malignant tumor of thymus complicated by ame- bic dysentery

Malignant thymoma (lympho-

Age -

40

40

9 mos.

19

25

38

28

9

Author

Meigs and de Schweinitz

y ( 5 )

Ilenault, Cathala, and Plichet (57)

Helvestine (58)

Ilelvestine

Priedlander and Foot (59)

Evert (60)

Miller (61)

lymph glands Spleen, liver, both kid-

neys

Not given

Date

1894

1923

1924

1924

1924

1925

1925

1926

Peribronchial lymph nodes

Sex -

M

M

?

F

M

1' colored

M

M

sarcoma) Lymphosarcoma

primary in thymus

1,yrnpho-epithe- lioma of thymus

Thymic lympho- cytorna, associated with lymphatic leukemia

Thymic lympho- cy toma (sarcoma)

Right pleura, right lung, pericardium, myocardium

Tumor was found a t operation and no metastasis

Spleen, lymph nodes (1)

Both pleurae, both lungs, mediast inal lymph nodes, perforation of sternum, diaphragm, both kidneys

First Series: Sarcoma of the Thymus (Thymoma) (continued)

Cnsc No. Aut,hor

I Date 1 Sex I Age

Brown, S. E. (69)

Matbras and Priesel (70)

Matras and Priesel

Matras and Priesel

Matras and Priesel

Shennan (71)

Shennan

Shennan

Shennsn

Shennan

Meeker (72), same case as reported hy H e r r i m n n and I t a h t e (73)

Holt (74)

Little anrl 1Jall (75)

Sarcoma of thymus

Lymp11os:~rcoma of thymus

I~yrnphosarcoma of thymus

IAymphosarcom:i of thymus

L y m ~ ~ h o s a r c o m a of thymus

ltound-cell sarcoma of thymus

iJymphosarcomn of thymus

Lyrnphosarcoma of thymus

Mal ignant thymoma, lymphatl- enoma type

Mal ignant t hy - moma, lymphad- enoma type

Mal ignant t hy - moma, lymphad- enoid type

Thymoma (thymic lymphosnr- coma)

Sarcorna of thymus

'I'hymoma (lymphosarcoma)

Metastasis

Both pleurae, hot11 lungs, mesc ,n t e r i c l y m p h notles, small intestines, left kidney

Pleura, per icar t l ium, thyroid gland, lymph glands of neck, right suprarenal gland, Iwth hitlneys, liver, pancreas

I'leuril, lungs, mediitstl- n:tl lyrnph gl:tnds

Left pleura, left lung

l'r:tcheal, bronchi:tl, cervical, supraclavicular lymph gl:tnds

l'ericardium, diaphragm

Pleura, lungs, pcricar- dium, m c d i a s t i n : ~ I lymph glands, both ventricles

llight cervical, met1i:ls- tinal lymph glands

I'ericilrdium, trt~chenl lyrnphglands, sternum, two upper right ribs, pectoral portion of left clavicle

llight pleura, right lung, mediastinal and gastric lymph glands, cl:~vicle, both scapulae, verte- brne, and ribs

ltight bronchus, trachea, right lung, right cervical, right ilxillnry inter- nal mammary, peri- vertebral, mesenteric lymph glands

Pleura, lungs, perihron- chid lymph nodes, retroperitoneal and I~ron- chi:rl l ymph nodes, stomach, kidneys, gastric lymph nodes

Bronchial lymph gl:inds, lungs, spleen

Hoth pleurae, lungs, diaphragm, cervical, gastric, a n d h e p a t i c lymph glands, liver, kidneys


First Series: Snrcon~n o j t he Thymus (Thymoma) (continued)

Author

--

Doub (76)

IinuLti (77)

Margolis (15)

Margolis

Margolis

Author's case

Age Date

--

1930

19:JO

1931

1931

1931

1931

1 Diagnosis I Sex

--

F

M

M

M

M

M

-- Thymoma ? (sar-

comatous)

Ly rr1phos:trcomn of thymus

Thymoma (lymphosarcoma)

I 'I'hymoma (modi-

fied lymphoszr- coma ?)

Thymoma (modi- fied lymphosarcoma 1)

Thymic lymphocytoma

Both pleurae, mediusti- nal, mesenteric and retroperitone:il lymph glands, spleen, pancreas, peritoneum

Both pleurae, lungs, kidneys, thyroid gland, lymph nodes, pericardium

Pericardium, both pleurae, both lungs, mediastinal lymph glands, both kidneys

Pericardium, left lung

Pericardium, right lung, attached to aorta and innominate artery

Both pleurae, both lungs, pericardium, myocardium

case previously reported by Ambrosini, and Rubaschow (30) doubted the origin of the tumors in several of the cases in Hoff- mann's collection (31); so that, as accurately as can be determined, the total number up to 1911 was 52. Of these, 44 were sarcomas and 8 carcinomas.

I n the first series tabulated in these pages are listed the cases of thymomata which were believed to be sarcomas, reported since 1911, together with others which were overlooked by previaus authors. The second series includes those cases believed to be carcinomas.

Since 1911, I have been able to review 78 cases of lymphosarcoma of the thymus. Including 44 cases collected by Rubaschow (30) the total number is now 122.

As regards sex, 45 c:tses occurred in males, 24 in females, and in 9 cases the sex was not stated. The oldest patient was eighty- six years old, the youngest four and one-half months. ' In 6 cases the age was not given. By far the larger number of cases occurred before the age of forty years.

A table of organs involved in cases of lymphosarcoma of the thymus indicates that not only do the tissues close to the original tumor become infiltrated, but distant organs are also affected. The data regarding metastasis wcrc givcn in 74 of the 78 cases. The

Organs Involved in Sarcoma of the Thymus

Organ I Lymph nodes

Neck . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Thorax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Abdomen

. . . . Hight lung 1, eft. lung . . . . . Pericardiuxn . . . Itight p1eur:t . . ideft 1)leura . . . . 1, eft kidney . . . Itight kidney . .

. . . . . . . . . Liver

Bones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sternum

Rib . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clavicle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vertebra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Humerus

Scapula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Spleen Myocardium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Vessels Innominate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Venacavn Carotid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mediastinal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Jugular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Aorta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Diaphragm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Irachea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Muscles Intercostal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ingeneral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

/ Thyroid gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Gastro-intestinl~l Stomach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Intestines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Peritoneum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Suprarenal glands Right . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Left

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Skin Left ovary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Central nervous system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Percentage .....

Second Series: Carcinoma of the Thynzus

Caw No. 1 Author

Eisenstiidt (78)

Sotgia (79)

Simmonds (80)

Iloccavilla (81)

I Vnnzetti (82)

Vanzetti

Strauss (16)

Gandy and PiCdeliCvre (R3)

Syrnmers and Vance (84)

Foot and Har- rington (85)

Jncobsen (86)

lineringer and I'riesel (87)

Honda and Taguchi (88)

FIonda and h Taguchi Honda and

Taguchi Cortese (89)

Lemann and Smith (90)

Brannan (22)

Age -

28

45

6'2

30

50

50

27

60

40

58

2

42

71

52

32

1 6'2

36

56 1

1 58

1 35

Date -- 1902

1910

1911

1912

1913

1916

1916

1919

1920

1921

1923

1923

1923

1923

1923

1923

1925

1926

1926

1926

Diagnosis Sex

M

M

M

M

M

M

F

M

M

M

1' col- ore, M

M

F

F

M

M

M

M

M

Carcinoma of thymus




Carcinoma of thymus (?)








Carcinoma of thymus, associated with tuberculous pleurisy




P r i m a r y carcinoma of thymus


Carcinomn of thymus


- Pericardiurn, lungs, chest

wall M e d i a s t i n a l l y m p h

nodes Pericardium, both plen-

rae, rnediastinal lymph nodes

I'leura, lungs, thor:~cio lymph nodes

lst, 2nd, and 3rd dorsal vertebrae, medullary spine

Both lungs, tracheal and bronchial lymph nodes

Left bronchi, trachea, vena cava, cervical vessels, mediastinal lymph glands

Pericardium, myocardium

No metastases described

Dorsal vertebrae, tlura, lungs

Both pleurae, both lungs

Mediastinal, retroperitoneal lymph glands, both lungs, liver, suprarenal glands, vertebrae

Both pleurae, pericardium, tracheobron- chial lymph nodes

I'leura, lungs, liver

P e r i c a r d i u m , costal pleura, superior vena cava, m e d i a s t i n a l lymph glands, sternal end of pectoralis major, liver, right femur

Vertebrae, liver, other abdominal organs (?)

Lungs, superior vena 1 cava, right kidney

Second Series: Carcinoma of the Thymus (continu.ed)

Case No. Author

Foot (91)

Reid (92)

ICai jser (93)

Lenz (94)

Danisch and Nedelmann (95)

Matras and Pr~esel (96)

Matras and Priesel

Matras and Priesel

Verga (97)

Zenoni (98)

Zajewloschin (99)

Nathan (100)

Duguid and Kennedy 001)

Bedford (102)

O'Flynn (103)

45

?

67

?

37

3t

62

56

:3.5

(72

72

40

40

64

New- born

52

Date -- 1926

1937

1927

1927

1928

1928

19'28

1928

1928

1928

1928

1928

1921

1930

1930

1931


Sex --

M

M

M

M

M

?

F

M

M

F

F

F

F

F

M

M




Primary epithelial tumor of thymus

Chrcinoma of thymus

1 Carcinoma of thymus


Carcinoma of thy- I mus

Choristoblastoma of thymus (car-

' cinoma) Pr imary carci-

noma of thymus

Adenocarcinoma primary in thymus

Lympho-epithe- lioma of thymus

Small-celled medullary carcinoma (oat-cell) primary in thymus


? Carcinoma of thymus

Metastasis 7---

Pleura, lungs, peribronchial lymph nodes, supraclavicular nnd axil- lary lymph nodes

Both pleurae, both lungs, diaphragm, liver

Pleura, lungs, liver

Pleura, lungs, liver

No metastasis

Hilus of each lung, brain, spinal cord, kidneys

No metastasis

No metastasis

Pericardium, medjaati- nal, p e r i b r o n c h i a l lymph glands, left kid- n eY

Right lobe of thyroid, deep muscles of neck, trachea

Both pleurae, lungs, mediastinal, c e r v i c a 1 lymph glands, pericardium, superior vena cava, liver

Pericardium, both pleurae, right lung, peribronchial, periaortic, cervical lymph glands

Pericardium, left pleura, left lung, mediastinal lymph glands

Pericardium, sternum, innominate vein, deep cervical glands, trtt- cheo-bronchial glands, epicardium, left pleura, ovaries, pancreas

Both lungs, bones, brain, liver, skin

Right pleura and luig, superior vena cava, left pleura and lung, right auricle and ventricle, liver, dorsal and lumbar vertebrae


table appearing on page 476 shows the organs involved, in the order of frequency.

Age Incidence of Snrconta of T h y m u s

Age Number of cases

- Under 5 months. . . . . : . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 months to 1 year.. 5 1 to 5 years. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 6 t o 10 years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 11to20years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 21to30years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 31to40years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 41to50years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Over50years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Per ccnt

The second series contains 36 cases of carcinoma of the thymus gland, all of which were proved by autopsy. As regards sex, 25 occurred in males, 10 in females. In one case the sex was not given. The oldest patient was seventy-two years old, and in one the tumor was found at birth. ' In 2 cases the age was not given.

,4ge Incidence of Carcinoma of the T h y n ~ u s

It is interesting to note that the majority of cases of carcinoma of the thymus occur after the age of forty. The majority of sarcomas of the thymus develop before the age of forty.

In three of the cases of carcinoma there was no metastasis, and in three no data concerning metastasis were given. The table on page 480 shows the organs involved in the order of frequency.

In both sarcoma and carcinoma of the thymus gland, the tissues in close approximation to the thymus are most often invaded. However, metastasis may take place to almost any tissue in the body.

Formerly, it was thought that the myocardium and the sternum were infrequently affected. This can no longer be considered cor-

Age - -

. . . . . . . . . . . Under 1 year.

Number of case6 -

- 1

Per cent ----

2.9 5.8 0.0 8.8

14.7 17.6 23.5 26.4

2

1 to 10 years.. . . . . . . . . . . 2 11 to 20 years. . . . . . . . . . . . 0 21 to 30 years. . . . . . . . . . . . 3 31 to 40 years. ........... 5

6 41 to 50 years.. . . . . . . . . . . 51 to 60 years. . . . . . . . . . . . Over 60 years. . . . . . . . . . . .

8 9 -

480 EDWARD H . CROSBY

rect. and metastasis below the diaphragm in malignant disease of the thymus should not be thought of as of rare occurrence . Al- though in carcinoma the lymph nodes of the thorax are as fre- quently infiltrated as in sarcoma. it will be noted that in carcinoma the abdominal lymph nodes were involved in only one case or 3.1 per cent. while in sarcoma the abdominal lymph nodes were affected

Orgarbs I~zvolz~ed in Curcinonm of the Thu. t )rz~s

Percentage ....

56.2 53.1 44.6 40.6

9.3 40.6 3.1

31.3 31.3

15.6 3.1 3.1

15.6 3.1 3.1

6.2 3.1 3.1

6.2 6.2 9.3 9.3

6.2

3.1 3.1 3.1 3.1 3.1 3.1 3.1 3.1

Organ

Left lung . . . . . . . . . . . . . . . . Itight lung . . . . . . . . . . . . . . Left pleura . . . . . . . . . . . . . . Right pleura . . . . . . . . . . . . .

Lymph nodes Of neck . . . . . . . . . . . . . . Of thorax . . . . . . . . . . . . Of abdomen . . . . . . . . . .

Pericardium . . . . . . . . . . . . . Liver . . . . . . . . . . . . . . . . . . .

Bones Vertebrae . . . . . . . . . . . . Sternum . . . . . . . . . . . . . Right femur . . . . . . . . . .

Vessels Venacava . . . . . . . . . . . Cervical . . . . . . . . . . . . . Innominate . . . . . . . . . .

Central nervous system Brain . . . . . . . . . . . . . . . . Dura . . . . . . . . . . . . . . . . Spinal cord . . . . . . . . . . .

Right kidney . . . . . . . . . . . . Left kidney . . . . . . . . . . . . . . Trachea . . . . . . . . . . . . . . . . . Myocardium . . . . . . . . . . . . .

Muscles Neck . . . . . . . . . . . . . . . .

Right suprarenal gland . . . . Left suprarenal gland . . . . . Diaphragm . . . . . . . . . . . . . . Thyroid gland . . . . . . . . . . . Anterior chest wall . . . . . . . Ovary . . . . . . . . . . . . . . . . . . Pancreas ................ Skin ....................

Freyueocy

18 17 15 13

3 13 1

10 10

5 1 1

5 1 1

2 1 1

2 2 8 3

2

1 1 1 1 1 1 1 1

MALIGNANT TUMORS OF THYMUS GLAND 48 1

in 17 cases or 22.9 per cent. In sarcoma of the thymus metastasis was found in the spleen in 11 cases, or 14.7 per cent, while in carcinoma of the thymus metastasis was not found in the spleen, These findings point to the fact that in sarcoma of the thymus, as in sarcoma elsewhere in the body, metastasis may occur more often by way of the blood stream, while in carcinoma metastasis tends to utilize the lymphatics. The central nervous system is more fre- quently involved in carcinoma than in sarcoma of the thymus, and the trachea and thyroid gland are infrequently the seat of infiltration and metastasis in both thymic sarcoma and carcinoma.

SUMMARY A typical case of thymic lymphocytoma is presented, in which

the diagnosis was made a t necropsy. The acute onset of symptoms and the rapidly fatal termination of the disease made diagnosis difficult and treatment futile. When such cases are seen early, x-ray therapy offers an excellent prognosis and even the hope of complete recovery.

A discussion of the clinical course of malignant tumors of the thymus and a review of the physical findings, including the typical x-ray shadow, indicate that diagnosis can often be made early, and in early diagnosis and x-ray treatment lies the only hope for the patient.

The embryology and histology of the thymus gland are reviewed.

One hundred and sixty-five cases of malignant disease of the thymus were found in the literature, which, with the case presented here, make a total of 166 cases. Of these, 122 were sarcomas, so- called, and 44 carcinomas. In all instances the diagnosis was con- firmed by necropsy or by biopsy.

A statistical review of 144 cases of malignant disease of the thymus gland is given with age and sex incidence, diagnosis, and site of metastasis. When the diagnosis was doubtful this fact is indicated and the case is listed as accurately as possible.

NOTE: The author is indebted to Dr. Thomas Ordway for the clinical history of the case presented and to Dr. Victor C. Jacobsen for the pathological report.

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47


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55. MEIGS, A. V., AND DE SCHWEINITZ, G. E.: Round-celled sarcoma of the anterior mediastinum, Am. J. M. Sc. n.s. 108: 193, 1894.

56. SWEANY, H . C.: Primary tumor of the thymus associated with tuberculosis, J. A. M. A. 80: 751, 1923.

57. RENAULT, J., CATHALA, J., AND PLICHET, A.: Ilyn~phocytoma of thymic origin, Bull. et. m6m. Soc. m6d. d. h8p. de. Par. 48: 176, 1924; Ahstr. J . A. M. A. 83: 1623, 1924.

58. HE:LVESTINF:, I?., JR. : Malignant tu~nors of the thymus, Arch Surg. 9: 309, 1924.

59. I?RIEDLANL)ER, A., A N D l ? o o ~ , N. (I.: 11~port on a case of m:ilign:inl, smttll-celled thymolna with ucutc lymphoid lcukcmis, Am. J. M. Sc. 169: 161, 1925.

60. EVERT, J . A.: Malignant tumors of the thymus; with report of a case, Minnesota Med. 8: 730, 1925.

61. MILLER, J . : A case of thymoma, Canadian M. A. J. 16: 810, 1926. 62. WOLLSTEIN, M., AND MCLEAN, S.: Hodgkin's disease, primary in

the thymus gland: report of :t case in an infant, Am. J. Dis. Child. 32: 889, 1926.

6'3. SCHMIDT, E. A.: Malignant mediastinal tumor, complicated by amoebic infection, Arch. Physical Therapy 7 : 558, 1926.

64. NOICIC, R. R.: Malignant thymoma, Minnesota Med. 10: 400, 1927. 65. ZANELLI, E:.: Lymphosarcoma of the thymus, case, Clin. Pediat.

9: 241, 1927. 66. BABES, A.: Ueber eine lymphoepitheliale Geschwulst der Schild-

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67. YOUNG, G. J., AND SPALDING, J , E.: Report of a case of lymphosarcoma of thymic origin with acute lymphoid leukemia, J. M. Soc. New Jersey 25: 609, 1928.

68. BROWN, W.: Thymoma simulating abdominal tumour, Brit. M. J. 2: 101, 1928.

69. BROWN, S. E.: Malignant tumor of the thymic region, with extensive metastases, Arch. Path & Lab. Med. 2: 822, 1926.

70. MATRAS, A., AND PRIESEL, A.: Dber einige Gewachse des Thymus, Beitr. z. path. Anat. u. z. allg. Path. 80: 270, 1928.

71. SHENNAN, T. : Tumors of mediastinum and lung, J . Path. Bnct. 31 : 365, 1928.

72. MEEKER, L. H.: Malignant thymoma: Iteport of a case, Tr:tns. N. Y. Path. Soc. Feb. 9, 1928, Arch. Path. 5: 928, 1928.

73. HERRIMAN, F. El., AND HAHTE, W. E.: Malignant thymoma with metastases, Am. J. Path. 5: 29, 1929. Also reported by Meeker, L. H.

74. HOLT, L. E.: cit. Jones, A. C. (1). 75. LITTLE, H. G., AND HALL, H. M.: Thymoma, West Virginia M. J.

26: 673, 1930. 76. DOUB, H. P.: Roentgen diagnosis and treatment of thymomata,

ltadiology 14: 267, 1930. 77. KNUTTI, R. 13.: Primary lymphosarcoma of the thymus with metas-

tases below the diaphragm, South. M. J. 23: 1104, 1930. 78. EISENSTADT, J . : Ueber Iirebs der Thymus, Inaug. Diss., Grcifswnld,

1902. Cit. by Brannan (22)) and Vanzetti (82). 79. SOTGIA, G. M.: Un carcinoma primitivo del timo, Arch. per le

sc. med. 42: 69, 1919. 80. SIMMONDS, M.: Ucber malignc Thymusgcschwulste, Ztschr. f .

I<rebsforsch. 12 : 280, 1913. 81. ROCCAVILLA, A.: Sopra una rara forma di mielite transversa second-

aria a reviviscenza neoplastica maligna di origine e tradiva di un thymus persistens, Riforma med. 29: 1037, 1913.

82. VANZETTI, F.: I tumori epiteliali del timo: di un caso di adenoma dcl reticolo timico, Arch. per le sc. med. 40: ,264, 1916.

83. GANDY, C., AND P I ~ D E L I ~ V R E , R.: Cancer of the thymus, Bull. et mCm. Soc. m6d. d. h6p. de Paris 44: 867, 1920. Abstr. J. A. M. A. 75: 704, 1920.

84. SYMMERS, D., AND VANCE, B. M: Epitheliomata of thymic origin, Arch. Int. Med. 28: 239, 1921.

85. FOOT, N. C., AND HARRINGTON, H.: Malignant epithelial thymoma: report of a case, with necropsy, Am. J. Dis. Child. 26: 164, 1923.

86. JACOBSEN, V. C.: Primary carcinoma of the thymus, Arch. Int. Med. 31: 847, 1923.

87. I~NERINGER, I<., AND PRIESEL, A.: Ein Beitrag zur Iienntnis der Thymome (Lymphoepithelioma thymi), Virchow's Arch. f. path. Anat. 241: 475, 1923.

88. HONDA, I., AND TAGUCHI, I<. : Ueber primiire bosartige Gcschwulste des Thymus, Gann 15: 57, 1921.


89. CORTESE, G.: Un caso di carcinoma primario della ghiandola del timo, Policlinico (sez. med.) 32: 417, 1925.

90. LEMANN, I. I., AND SMITH, J . : Primary carcinom:~ of the thymus; report of a case, Arch. Int. Med. 38: 807, 1926.

91. FOOT, N. C.: Concerning "malignant thymoma" with report of a case of primary carcinoma of the thymus, Am. J. Path. 2: 33, 1926.

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schluss an zwei eigene Falle von Thymuskarzinom, Acta. path. ct microbiol. Scandinav. 4: 221, 1927.

94. LENZ, R . : Berichte iiber einen Thymustumor, Wien. med. Wchnschr. 78: 224, 1928.

95. DANIS~H, F., AND NEDELMANN, E.: Bijsttrtiges Thymom bei einern 34 jiihrigen Kind nit eigenartiger Metast,asierung ins %entr:~l- nervensystem, Virchow's Arch. f. path. Anat. 268: 492, 1928.

96. MATRAS, A., A N D PRIESEL, A.: Uber einige Gewiichse des Thymus, Beitr. z. path. Anat. u. z. allg. Path. 80: 270, 1928.

97. VERGA, P.: Coristoblastoma timico a sede tiroidea, Pathologia 20: 118, 1928.

98. ZFNONI, C.: Cancro mediastinico timogeno, Rev. sud-am. dc en- docrinol. 11 : 597, 1928.

99. ZAJ~:WLOSCHIN, M. N.: Zur Kasuistik der Geschwiilste thymogcnrn Ursprungs: "Adenokarzinoma Thymus," Frankfurt. Ztschr. f. Path. 37: 36, 1929.

100. NATHAN, W.: ifber einen Fall von Ilymphoepithelioma Thymi, Frankfurt. Ztschr. f. Path. 37: 385, 1929.

101. DUGUID, J . B., AND KENNEDY, A. M. : Oat-cell tumors of mediastinal glands, J . Path. & Bact. 33: 93, 1930.

102. BEDFORD, G. V.: A case of carcinoma of the thymus with extensive mctastases in a new-born child, Canadian M. A. J. 23: 197, 1930.

103. O'FLYNN, J. A.: A malignant tumor of the thymus gland, J. Roy. Nav. M. Serv. 17: 5, 1931.

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