Primary Hodgkin's Disease of the Thyroid: '

Report of a Case and Review of the Literature

T. W. ROBERTS, M.D.,** RUDOLPH G. HOWARD, M.D.* *

From the Department of Pathology, Delaware Hospital, Wilmington, Delaware

Introduction

ANY of the varied forms of malignantlymphoma may be found in the thyroidgland when the disease is generalized.Very rarely, the thyroid is the only obvioussite of tumor. In such primary lymphomas,the issue is usually rapidly fatal. The onlyfive-year survivors are patients in whomthe disease was localized and x-ray therapywas prompt and adequate.Of the primary lymphomas of the thy-

roid, Hodgkin's Disease is by far the rarest.Only a few sporadic reports have occurredin the world literature since 1900. Wegelin21in his encyclopedic treatise on the thyroidin 1926, categorically stated that primaryHodgkin's of the thyroid was then un-

known. In 1930, Kramer7 reported one

case of this condition treated with subtotalthyroidectomy and x-ray therapy with a 10-year survival. Six years later Sternberg 15 in

his review of 53 cases of Hodgkin's Diseaseat necropsy mentioned two cases whichwere primary in the thyroid and PresnoBastiony 12 reported one case in the Spanishliterature. Cohen and Moore,2 in their re-

view of 101 cases of malignant tumors ofthe thyroid, included one primary Hodg-kin's disease. Rovello 13 published a de-tailed case with a discussion of early histo-pathologic changes. He also reviewed twoprevious cases, Brusa (1932) and Mayerand Jasch (1934). This also was the yearwhen Meissner in a seminar on tumors ofthe head and neck, discussed a case which

Submitted for publication June 14, 1962.** Present address: Department of Pathology,

Albert Einstein College of Medicine, Bronx 61,N. Y.

he believed was primary Hodgkin's diseaseof the thyroid. Finally, Smithers 17 men-tioned three cases of his own which he be-lieved to be primary Hodgkin's of the thy-roid in a lecture to the Faculty of Radiolo-gists on thyroid tumors.The extreme rarity of this lesion, a pro-

longed period of localization, make the fol-lowing case worth reporting.

Case ReportA 61-year-old white man was admitted to the

Delaware Hospital on March 22, 1958 because ofa painful, progressively enlarging mass in the neck.Eleven years previously the patient had a sub-total thyroidectomy. The tissue diagnosis wasHashimoto's disease. Two months prior to admis-sion, he noticed tightness of his collar which pro-gressed to the degree that he could no longerbutton his shirt. Pain radiated from the anteriorcervical region to the angle of the mandible.

On physical examination there was a hardmass in the right neck which caused gross devia-tion of the trachea and right vocal cord paralysis.At operation, a transverse incision was made inthe line of the old thyroidectomy scar. The largehard, fixed tumor mass arising from the right sideof the neck in the region of the right lobe of thethyroid was exposed by separating and retractingthe ribbon muscles. The tumor was found to ex-tend into the mediastinum and invaded the tra-chea and carotid sheath. For these reasons noattempt was made to remove the adherent tumorinvolving vital structures. A fairly large portionwas resected and with one of the regional lymphnodes was submitted for pathological sttudy. Atracheostomy was performed and after an un-eventful course, the patient was discharged 14days after admission.

Gross Description: The specimen was re-ceived in the fresh state as a hard, grayish-pinkmass measuring 4.0 X 3.0 X 3.0 cm. Remnants ofa capsule were noted on one surface. The tumorwas composed of smaller nodules varying in sizefrom 1.0 to 2.0 mm. The cut surface was irregu-

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626 ROBERTS AND HOWARD

larly traversed by yellow to gray tissue with oc-casional chalky deposits. Tissue suibmitted forfrozen section was reported as stispiciotis formalignant change. A lymph node measured 1.5 x0.5 cim; when sectioned, the tissuie was pink andhiomogeneous.

Microscopic Description: Sections of tissuefrom the 1958 biopsy specimen showed oblitera-tion of thyroid parenchyma by a celltular growthwith the pattern of a lymphomna. There is a gen-erouis admixture of polymorphontuclear leukocytesin which there are scattered eosinophils. The cel-lutlar infiltrate demonstrates moderate pleomor-phismii with numerous large formis resemblingReed-Sternberg cells. Elsewhere, there is a finefibrosis as well as foci of necrosis (Fig. 1).

Review of slides from the lobectomy specimenremoved in 1946 shows a similar histological pat-tern with slight variation. These sections containresidual thyroid follicles witlh Huirthle cell hyper-plasia. There is scant inflammiatory cell infiltrationand abtundant Reed-Sternberg cells. It is apparentat this time that the two lesions are identical(Fig. 2). Reticulum stains demonstrate fiberswinding abotut individuial cells lending sUpport toa mesodermal origin of these cells. The sections

Annals of SurgeryApril 1963

FIG. 1. A. RecurrentHodgkin's Disease in re-sidual thyroid gland re-moved in 1958 ( x 35).Note the absence of fol-licles.

of lymph node show lymphoid hyperplasia withno malignant characteristics.

Following the operation in 1958, tanned cellhemaggltutination tests performed in Dr. Witeb-sky's laboratory were reported positive in diltu-tions of 1: 1,280.

A third admiiission of the patient is notedthrough correspondence with the MIilford MlemorialHospital (Delaware) in January 1961. At thistime he presented with a rupture of the lower endof the ileuim duie to a growth diagnosed by Dr.Arthutr Ptirdy Stouit as a retictluinm cell sarcomia.

DiscussionIn our review of the literature we were

only able to cull 12 cases from the mass ofreports of primary Hodgkin's disease of thethyroid (Table 1). In only two were de-tailed clinical and pathological reportsgiven. The fact that the presently reportedcase is so carefully documented makes itall the more interesting.The original diagnosis was Hashimoto's

Disease. This is uinderstandable in view of

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the fact that criteria for the diagnosis ofHashimoto's Disease are in general dis-agreement.20 Slides from 1958 and 1946have been reviewed by several leadingpathologists including two who have a spe-cial interest in thyroid and lymphoid tissuediseases. They agreed that both lesions arethe same and are consistent with the diag-nosis of Hodgkin's disease.The possible association of Hashimoto's

disease with malignant lymphoma has beenunderscored by several authors, Grahamand McCullagh,5 Lindsay and Dailey," andWValt, WA7oolner and Black.lo Smithers 17 dis-ctusses two cases, which indicates there canbe such an association, although they donot conclusively prove that Hashimoto'sdisease preceded the development of Hodg-kin's Disease. The first was a man 57 yearsold, who had had a goiter removed forHashiimoto's Disease, then 14 months laterdeveloped acute fulminating Hodgkin's

Fig. 1. B. Residualfollicles in area of Hodg-kin's Disease of thyroidgland removed in 1958(X 440). Higher magni-fication showing pleo- "A

morphism with Reed-Steinberg cells and fi-brosis.

1)ISEASE OF THYROII) 627

Disease in the neck and mediastinum anddied within two months. The second was a35-year-old woman who had a partial thy-roidectomy for Hashimoto's Disease. Eight-een months later, she had a rapid "pleo-morphic cell lymphosarcoma" in which thedominant cell was the reticulum cell.Antibody formation in our case, does not

unequivocally support the relationship withHashimoto's Disease since there is evidencewhich suggests that malignant lymphomasare able to elicit immune responses.1Lymphoma in the small intestines 13

years after the tumor in the thyroid hadbeen diagnosed, raises again the questionof association of gastro-intestinal ttumorswith primary lymphomas of the thyroid.Such cases have been reported by Dick andKellet,4 Brewer and Orr I and McKenzie,Moore and Fidler."0 Records of more than24 necropsies are now available ) 10, 1which showv that of 16 cases in which there

.- - . .- - - - - , ...

ROBERTS AND HOWARD Annals of SurgeryApril 1963

FIG. 2. A. Section ofsubtotal thyroidectomy,1946 (x 170). Hodgkin'sDisease with residual fol-licles.

FIG. 2. B. Section ofsubtotal thyroidectomy,1946 (X 35). Anotherarea showing destructionof most of the folliculararchitecture.

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FIG. 2. C. Section ofsubtotal thyroidectomy,1946 (x 440). Showingpleomorphism and Reed-Stemnberg cells.

FIG. 3. A. Section ofterminal ileum removedin 1961 (x 35). Showingreticulum cell sarcoma in-volving mucosa and sub-mucosa.

PRIMARY HODGKIN'S DISEASE OF THYROID 629

ROBERTS AND HOWARD Annals of SurgeryApril 1963

FIG. 3. B. Anotherview of terminal ileum(removed in 1961) (x35). Showing involve-ment of the circular layerof muscularis.

FIG. 3. C. Small in-testine (terminal ileum)1961 (X 440). Highermagnification demonstrat-ing a lymphomatous pat-tern composed of reticu-lum cells and pleomor-phism.

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PRIMARY HODGKIN'S DISEASE OF THYROID

TABLE 1. Primary Hlodgkins Disease of the Thyroid

No. Akge &Cases Sex Survival Remarks

Kramer, 1930

Sternberg, 1936

Presno y Bastiony, 1936

Cohen & Moore, 1954

Rovello, 1955

Meissner, 1955

Smithers, 1959

Roberts & Howard, 1962

1 48F

12 yrs.

2

1 18F

1 -

3 28F

1

3 32F57M

1 61M

Treated by subtotal thyroidectomy andx-ray, died 12 yrs. later with generalize(dlymphoma.

Discussed 2 cases in an autopsy series of53 cases of Hodgkin's Disease.

3 yrs + Nodule present 1 year before surgery

(subtotal thyroidectomy).

One case of Primary Hodgkin's Disease inseries of 101 malignancies.

13 weeks Subtotal thyroidectomy (Hodgkin's Dis-ease). Regional lymph node showed earlxchanges. Discussed case of Brusa. Dis-cussed case of Mayer E. Jasch.

Discussed as a case in Seminar on Head& Neck Tumors.

7 yrs. Subtotal thyroidectomy and x-ray. Sub-16 mos. total thyroidectomy diagnosed as Hash-

imoto's disease. Died 16 mos. later offulminating Hodgkin's Disease. Men-tions a 3rd case.

13 yrs. Subtotal thyroidectomy-diagnosed as

Hashimoto's disease. Recurrence 11 yrs.

later. One year later developed tumorof small intestine. Diagnosed as reticu-lum cell sarcoma.

was distant metastases of lymphoma fromthe thyroid 14 involved the gastro-intestinaltract. It is, however, difficult to assume thatsuch gastro-intestinal tumors are secondaryto the primary thyroid tumor. An alterna-tive explanation according to Metcalfe andSclave 11 would be the multifocal origin ofthe tumor. Such multifocal origin of lym-phoma within the gastro-intestinal tract isof course not uncommon.6 It may be thatthe thyroid is sometimes the initial mani-festation of a lymphoma whose site oforigin is in the gastro-intestinal tract.The fact that the tumor in the thyroid

was Hodgkin's Disease and the intestinallesion was reticulum cell sarcoma does not

confute the inter-relationship since in a

study of 1,300 cases of malignant lym-phoma, Custer and Bernhard 3 noted thatonly 20 per cent maintained a pure type of

histologic pattern. Approximately 40 percent underwent complete transition from

one histologic type to another. The remain-ing 40 per cent included combinations ofhistologic types observed in different por-

tions of the tissues.Ten cases of lymphoma of the thyroid

described by Brewer and Orr were associ-ated with two sharply differing types ofclinical courses. Six patients died within a

few months and the others remained alivefor relatively long periods. Examples of un-

expectedly long survivals and an associa-tion with similar tumors in the gastro-in-testinal tract led the author to postulatesome unusual type of granulomatous reac-

tion with a predilection for thyroid and in-testinal wall. Since no histological distinc-tion could be made between rapidly fatalcasts and those which ran a benign course,

they suggested the term Struma Reticulosabe used until more data becomes available.

Subsequent reports (McKenzie et all10and Canney have not elucidated this ex-

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Author & Year

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632 ROBERTS AND HOWARD Annals of Surgery632 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~April 1963

tremely rare and interesting association.The present case is another to be added tothat very exclusive group of primary Hodg-kin's Disease of the thyroid as well as an-other addition to the still smaller groupwith intestinal involvement. Because of therelatively benign course-accurate classifica-tion of benignancy or malignancy mustawait additional cases and follow ups.

SummaryA case of primary Hodgkin's Disease in

the thyroid gland which remained localizedfor 12 years is presented. Attention is calledto the association of thyroid and intestinallymphomas and the apparently good prog-nosis. A comment is made on the rarity ofthe lesion and the literature is discussed.

AcknowledgmentWe acknowledge with sincere appreciation the

assistance of Dr. Arthur Purdy Stout (ProfessorEmeritus of Surgical Pathology, College of Physi-cians and Surgeons, Columbia University) and Dr.Alfred A. Angrist (Professor and Chairman, De-partment of Pathology, Albert Einstein College ofNMedicine, Yeshiva University) who reviewed themanuscript and microscopic sections.

Bibliography1. Brewer, D. B. and J. W. Orr: Struma Reticu-

losa: A Reconsideration of the Undiffer-entiated Tumours of the Thyroid. J. Path.Bact., 65:193, 1953.

2. Cohen, M. and G. E. Moore: Malignant Le-sions of the Thyroid. Surgery, 35:62, 1954.

3. Custer, R. P. and W. G. Bernhard: The Inter-relationship of Hodgkin's Disease and OtherLymphatic Tumors. Am. J. Med. Sc., 216:625, 1948.

4. Dick, A. and H. S. Kellett: Reticulosarcoma ofthe Thyroid Gland, Brit. J. Surg., 39:257,1951.

5. Graham, A. and E. P. McCullagh: Atrophyand Fibrosis Associated with Lymphoid Tis-sue in the Thyroid: Struma Lymphomatosa(Hashimoto). Arch. Surg., 22:548, 1931.

6. Jequier, M.: Deux Sarcomes au Debut de LeurEvolution-Etude sur la Pathogenese desTumeurs. Bull. Assoc. Franc P. l'Etude duCancer, 23:617, 1934.

7. Kramer, E.: Beitrag zur Chirurgie der Lym-phogranulomatose. Arch. f. Klen. Cher., 160:234, 1930.

8. Lindsay, S. and M. E. Dailey: MalignantLymphoma of the Thyroid Gland and itsRelation to Hashimoto's Disease. J. Clin.Endocrin., 15:1332, 1955.

9. Massini, M. A.: Uber die Sarcome derSchilddruse mit besonderer Berucksichtigungder Lympho und Retothelsarkome. Schweiz.Z. Allg. Path., 19:259, 1956.

10. McKenzie, A. D., J. R. Moore and H. K.Fidler: Cancer of the Thyroid: Undiffer-entiated and Miscellaneous Carcinomas.Canad. J. Surg., 2:73, 1958.

11. Mletcalfe, W. J. and G. Sclare: Primary Lym-phosarcoma of the Thyroid. Brit. J. Surg.,48:541, 1961.

12. Presno, Y. and J. A. Bastionony: Enfermedadde Hodgkin de Localizacion Primitiva en laRegion Tiroidea Simulando un Bocio. Rev.de Med. y cir. de la Habana, 41:213, 1936.

13. Rovello, F.: Linfogranuloma Primitivo dellaTiroide: Studio Morfologico della AlterazioniIniziale del Morbo de Hodgkin. Haemat.,40:477, 1955.

14. Scarzella, NI.: Sulle Localizzazioni Rare delLinfogranuloma Maligno. Mlinerva MIed., 1:448, 1930.

15. Sternberg, C.: Lymphogranulomatose undReticuloendotheliose. Ergebn. d. Allg. Path.u. Path. Anat., 30:1-76, 1936.

16. Stout, A. P.: Lymphosarcoma and Hodgkin'sDisease. Rhode Island Med. J., 32:436, 1949.

17. Smithers, D. W.: Tumours of the ThyroidGland in Relation to Some General Con-cepts of Neoplasia. J. Faculty of Radiol.,10:3, 1959.

18. Walt, A. J., L. B. Woolner and B. NI. Black:Primary Mlalignant Lymphoma of the Thy-roid. Cancer, 10:663, 1957.

19. Walt, A. J., L. B. Woolner and B. NI. Black;Small Cell Malignant Lesions of the ThyroidGland. J. Clin. Endocrin., 17:45, 1957.

20. Warren, S. and Meissner, W. A.: Tumors ofthe Thyroid Gland. A. F. Inst. Path., Fascicle14. Washington, D. C., 1953.

21. Wegelin, C.: in Handbuch der SpezellenPathologeschen Anatomie und Histologie.Henke F., and 0. Lubarsh, Editors, Vol.VIII, P. 134, Julius Springer, Berlin, 1926.

22. Welch, J. W., V. E. Chesky and C. A. Hell-wig: Mlalignant Lymphomas of the Thyroid.Surg. Gynec. & Obst., 106:70, 1958.