transcervical thymic biopsy in children with immunodeficiency

Transcervical Thymic Biopsy in Children With Immunodeficiency

By Richard Hong and John W. Pellett

• To more fully characterize immunodeficiencystates, thymic biopsies add useful information. Thetranscervical technique is simple and does not requirea sternal-splitting procedure. The thymus was muchlarger than anticipated in 12 of 12 cases so far biop­sied, including six cases of severe combined im ­munodeficiency. A sample of 2-3 gm was readilyremoved. A slight wound infect ion was encounteredin only one instance: no generalized septic episoderesulted.

INDEX WORDS: Thymic biopsy. transcervical; im­munodeficiency.

T HE USE of cultured thymic epithelium(CTE) as a treatment modality offers a

new approach not only for the more severe im­munodeficiency disorders, but for many moresubtle, less defin ed, deficienci es of the thymic(T cell) system of immunity" In attempting tounderstand the mechanism of CTE reconstitu­tion, and to further define the role of the thymusin hum an immunobiology, it has become im­portant to obtain small biopsies of the thymusfor histologic assessment and function alstudies ." Although a number of tests are nowavailable to test the function of T cells in theperipheral blood, the actual capability of thethymic epithelium cannot be dire ctly inferredfrom these assessments. We have observed thatanatomical changes can far exceed the degreeof abnormality that would have been predictedfrom the in vitro tests of T-cell function. Whenonly postmortem tissue is available for his­tological evaluation, the effects of a severe, ter­minal, stressful illness add marked involutionalchanges to the morphological picture of theba sic disease process. Finall y, lymphoid tissuecan show gr adual attrition over a period ofseveral yea rs so that autopsy examination maynot record the ea rly changes.

There appears to be great reluctance toperform thymic biopsy since the patients areoften severely ill, small infants, and, it is feltthat adequate assessment is available fromblood studies. For the reasons sta ted abo ve, wefeel that addit ional information is no wnecessary . The purpose of this article is todescribe the relative simplicity of the operativetechnique and to encourag e its more widespreaduse in the assessment of the thym ic syste m.

Journal of Pediatric Surgery. Vol. 13. No.4 (August). 1978

OPERATIVE TECHNIQUE

As the thymus is usually high in the mediastinum, asternal-splitting incision is unnecessary, and the trans­cervical approach is more than adequate.v ' General endo­tr acheal anesthesia is employed. The patient is positioned asfor a mediastinoscopy or throidectomy. A 3-cm transversecurvilinear incision is made one fingerbreadth above the su­prasternal notch . The sk in, subcutaneous tissue , andplatysma muscles are divided, bleeders being controlledwith electrocautery. The strap muscles are separated in themidline, opening the suprasternal space. Immediatelybeneath the strap muscles, and lateral to the midline, thethymus is readily encountered; the upper pole is just visiblein the wound, just above the level of the suprasternal notch(Fig. IA). It is easily recognized as a pale, pinkishstructure,just deep to the sternothyroid muscle. It is surprisinglylarge , considering the usual autopsy description of thethymus in severe combined immunodeficiency syndromes:'The upper pole is delivered into the sound with gentle trac­tion care taken to avoid avulsion of veins draining into theinnominate vein. A small pieceof thymus is removed for his­tologic assessment and functional study. It is not necessaryto dissect extensivelybelow the level of the sternal notch asis required in a transcervical total thymectomy.The amountremoved is estimated to be about one-third of a single lobeand measures approximately 0.7 x 0.7 em. Bleeding fromthe thymus is controlled with fine suture ligatures. Themajor vessel encountered in the dissection is the innominatevein, which is j ust subjacent to the thymus lobe. The musclelayers are reapproximated with interrupted sutures and theskin closed with a subcuticular suture. No drainage is em­ployed. To date, no complicat ions have occurred, except asmall easily controlled wound infectionon one occasion.

DISCUSSION

We have performed the procedure 12 times inpatients with the diagnoses as shown in T able I.One of th e most striking observations is that thethymus is easily found, even in the children withsevere combined immunodeficiency; this is inpart related to the failure of the gland todescend norm ally into the mediastinum. Also,the gland is much larger than observed at

From the Departments of Pediatrics and Surgery,University of Wisconsin, Center for Heal th Sciences,Madison . Wis. 53706.

Support ed In part by Grants HD 07778 and Al-J0404f rom the Natianal Institutes of Health and by the NationalFoundat ion.

A ddress reprint requests to Richard Hong. M.D., De­partments of Pediatrics and Surgery, University of Wis­consin, Centerfor Health S ciences. Madison. Wis. 53706.

© 1978 by Grune & S tratton, Inc.0022-3468/78/1304-0018$01.00/0

427

428

c

, l'V~ rstrap muscles' sternomastoid

retracted /'-- - - -'sternothyroidupper'po/.

right thymul lob.

---_...

HONG AND PELLETT

Fig. 1. (A) Site of incision 1 fin­ger·breadth above suprasternalnotch. (B) Strap muscles have beenretracted on the right; position ofthe upper pole of thymus is indi­cated. Strap muscles on left left inoriginal position for orientation. Ie)Strap muscles have now beenretracted bilaterally and the thymusdelivered into wound. Biopsy of anyconvenient size is readily accom­plished.

autopsy. In contrast to the small vestigial organwhich seldom weighs more than 1-2 g atautopsy, we are impressed with the size of thegland as visualized at surgery. A biopsy weigh­ing 2-3 g is routinely removed and we estimate

Table 1. Diagnoses of Patients

Severe combined immunodeficiency

Common variable immunodeficiency

Selective IgM deficiency

Isolated T-cell deficiency

Ataxia telangiectasia

Chronic mucocutaneous candidiasis

6

11

1

2

1

that this represents, at most, 25% of the totalmass. We have yet to encounter a child withoutan easily detectable thymus.

Studies performed include the culture ofthese glands with normal and diseased bonemarrow, peripheral blood to study cell interac­tion , and measurement of culture supernatantfor thymic "hormones." A detailed report ofthese observations will be reported elsewhere."

We suggest that thymic biopsy is a useful, ad­ditional study in the total assessment of im­munity, and that it can be performed quicklyand simply without undue harm to the patient.

REFERENCESI. Hong R , Santosham M, Schulte-Wissermann H, et al :

Reconstitution of Band T lymphocyte function in severecombined immunodeficiency disease following transplanta­tion with thymic epithelium. Lancet 2:1270-1272 , 1976

2_ Hong R, Horowitz SD: Thymosin therapy creates a" Ha ssall" (?) . N Engl J Med 292:104,1975

3. Kirschner PA, Osse rman KE, Kark AE: Studies inmyasthenia gravis ; transcervical total thymectomy. JAMA209:906-910,1969

4. Lore JM: An Atlas of Head and Neck Surgery.Philadelph ia, WB Saunders, 1973, pp 653-656

5. Hoyer JR, Cooper MD , Gabrielsen AE, et al :Lymphopenic forms of congenital immunologic deficiency :Clinical and pathologic patterns. In Bergsm a D, Good RA(eds) Immunologic Deficiency Disea ses in Man. New York,The National Foundation, 1967, pp 91-103

6. Schulte-Wissermann H, Horowitz SD , Borzy M, et al:(manuscript in preparation)