J. clin. Path. (1965), 18, 43

Diagnostic problems in biliary duct lymph nodesGEORGE WILLIAMS AND J. S. WHITTAKER

From the Department ofPathology, University of Manchester

SYNOPSIS Lymph nodes in the area of the cystic duct are sometimes included with surgicallyremoved gall bladders for pathological examination. These nodes may show a range of histologicalchanges, including sinus histiocytosis and panhyperplasia with, or without giant cell systems,granuloma and fibrosis. The nature and incidence of these changes were studied with appropriatelymph nodes collected routinely from 80 patients, mainly at necropsy. Awareness of these changesshould obviate possible serious error in histological diagnosis.

The lymph nodes draining the gall bladder,commonly situated near the cystic and hepatic bileducts (Fig. 1) are sometimes included in cholecystec-tomy specimens received for pathological examina-tion. Two or more lymphoid masses, varying in size(up to 2 cm. in diameter) may be present.The histological appearances of these nodes range

from normal through a simple reactive hyperplasiato a more pleomorphic picture in which numerousgiant cells and even granulomata may be found.These latter changes in particular may pose adiagnostic problem to anyone unfamiliar with thehistological appearances of lymph nodes in this site.Attention has been drawn to this problem in theU.S.A. by Aponte (1960) but we have been unableto find any comparable study in the Britishliterature.

FIG. 1. Enlarged lymph node (arrow) near junction ofcystic and hepatic bile ducts.Received for publication 20 March 1954.

Accordingly, a series of lymph nodes from thecystic duct area was collected from patients atnecropsy, or as surgical specimens, with a view toestablishing the frequency and nature of thesehistological changes.

MATERIALS AND METHODS

Lymph nodes from the area of the cystic duct wereexamined from 80 patients of ages ranging from 28 to 79years, 77 being routine necropsy and three biopsy speci-mens. The only patients excluded from the series werethose suffering from a reticulosis of any kind. Afterfixation in 10% formalin saturated with mercuric chloride,paraffin sections were stained with haemalum and eosin;specimens fixed in a formalin-cetylpyridinium chloride(C.P.C.) (Williams and Jackson, 1956) were stained bythe periodic-acid-Schiff and Hale's colloidal irontechniques for glycoprotein and acid polysaccharides.Formalin-fixed tissue and fresh frozen cryostat sectionswere also examined for fat content. Sections of gallbladder were also taken from some of the cases. In 14cases, lymph nodes were simultaneously taken from thepara-aortic and deep cervical chains and the axilla forcomparison.

RESULTS

Of the 80 patients studied, 43 had normal lymphnodes; the remaining 37 produced pathologicalnodes in which sinus histiocytosis, histiocytosis orpanhyperplasia accompanied by giant cell systemsor granulomata, and fibrosis, were the principalabnormalities. The incidence of these changes isseen in Table I.

NATURE OF THE HISTOLOGICAL CHANGES

GROUP I: NODES SHOWING SINUS HISTIOCYTOSIS Thiswas the largest group showing abnormal nodes.

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TABLE IINCIDENCE OF LYMPH N

Histology

NormalSinus histiocytosisSinus histiocytosis with granulomata ISinus histiocytosis with giant cells fPanhyperplasia with giant cellsFibrosisTotals

Their main feature was a hyp(Fig. 2), some containing finedilated sinusoids; plasma cellplasia were not pronounced; i

this group contained prominedistributed both in macrophageSome of this pigment, mainly treacted histochemically forcontaining pigment was P.A.Sfast, and therefore probably nbile pigment, including metiiodine-thiosulphate, and Fouc1960) were also negative. A pobtained, however, with Sudan

GROUP II: NODES SHOWING GIANT CELLS The

IODE LESIONS histological appearances of this group were interest-Group No. of Cases ing and striking. Giant cells were prominent and of

two distinct types, one multinucleated with foamyI 43 (54 0%) cytoplasm containing lipid and sometimes pigment,I I 122 (27-5%)

occurring singly or as aggregates around fatty10 Jl3 (16-0%) globules (Fig. 4). Sinus histiocytosis similar to that

III 2 (25%) in group I nodes was a feature of this group. The80(100%) other form of giant cell was mononucleated with

densely aggregated nuclear chromatin and baso-philic or clear, lipid-free cytoplasm (Fig. 5). These

erplasia of histiocytes were particularly prominent in two surgicallylipid droplets lining removed specimens showing panhyperplasia of theand lymphoid hyper- nodes.nine nodes (41 %) of Granulomata, composed of large, pale macro-Mnt pigment deposits phage epithelioid cells, were present in a third-s and extracellularly. surgical specimen (Fig. 6) in conjunction with sinushe intracellular form, histiocytosis. Eosinophil leucocytes were alsoiron; the non-iron- featured prominently in three nodes in this group.).-negative, non-acid-iot ceroid. Stains forhylene blue, Stein'svhet's reagent (Hall,)ositive reaction wasBlack (Fig. 3).

GROUP III: NODES SHOWING FIBROSIS Although onlytwo in number, the specimens are grouped separ-ately on account of their extensive fibrosis, presum-ably of post-inflammatory type in the absence ofother significant changes.

,,,k,,X,:2S' 3WFIG. 2 FIG. 3

FIG. 2. Lymph node showing proliferation of histiocytes within dilated sinusoids. Haemalum and eosin x 55.FIG. 3. Pigment deposits (arrow) associated with fat globules in lymph node macrophages. Sudan black andneutral red x 400.

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Diagnostic problems in biliary duct lymph nodes

FIG. 4. Multinucleated lipid-laden giant cells and smallermacrophages. Haemalum and eosin x 200.

FIG. 6. Granuloma formed of pale epithelioid macro-phages. P.A.S./haematoxYlin x 250.

FIG. 5. Mononucleated giant reticulum cells as part oflymph node panhyperplasia. Haemalum and eosin x 450.

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DISCUSSION

Sinus histiocytosis, the most common feature of thepathological nodes, was the sole lesion in 27 5% ofcases, and associated with giant cell systems orgranulomata in a further 14% of cases. According toMarshall (1956), sinus histiocytosis represents ahyperplasia of macrophages in nodes draining fociof tissue damage. In the present context it reflectsthe frequency of gall bladder disease, although acorrelation between the two was prevented by theautolytic changes in most of the gall bladderspecimens obtained at necropsy. Lymph nodepanhyperplasia involving the formation of secondaryreaction centres, plasma cell proliferation in themedullary cords as well as hyperplasia of sinushistiocytes, was present in only two specimens oftheseries removed surgically in conjunction with gallbladders showing active chronic inflammatorychanges.The most striking histological feature of the whole

series was the presence of giant cells (group II).Multinucleated forms of macrophage type were

invariably associated with hyperplasia of sinushistiocytes from which in all likelihood they werederived by fusion. Many contained lipid or

were associated with large extracellular lipiddroplets. In one case, as Touton giant cells, theyfeatured in multiple granulomata. Pigment depositswere present in less than half of the nodes of thisgroup, indicating that lipid was the main stimulus tothe formation of this type of giant cell. The othergiant cell form, mononucleated and lipid-free, wasregarded as a primitive reticulum cell formed as

part of a lymph node panhyperplasia in response toactive gall bladder inflammation. In one instancethey were sufficiently numerous to suggest areticulosis; none, however, showed mirror-imagenuclear forms and the remainder of the nodestructure indicated a brisk reactive hyperplasia.The macroscopic green or brown deposits in

group II nodes were most likely of bile origin.Failure to confirm this by various histochemicalmethods may have been due to complexing of thebile pigment with lipid as indicated by an affinity forSudan Black and to a lesser extent for Sudan IV.

In 14 of the cases, three of which showed pro-minent histiocytosis and giant cell systems, lymphnodes taken from the deep cervical, axillary, andpara-aortic regions for comparison showed normalappearances.The lymph node changes described in this series

indicate the range of histological variation whichmay affect lymph nodes in this region. As such theyare regarded essentially as local phenomena and of areactive nature. Appreciation of these points wouldserve to avoid serious errors in histological interpret-ation.

We are indebted to Messrs N. Mowat, J. T. Stopford,and G. Saville for help with photography and thehistological preparations.

REFERENCES

Aponte, G. E. (1960). Amer. J. clin. Path., 34, 57.Hall, M. J. (1960). Ibid., 34, 313.Marshall, A. H. E. (1956). An Outline of the Cytology and Pathology

of the Reticular Tissue. Oliver and Boyd, Edinburgh.Williams, G., and Jackson, D. S. (1956). Stain. Technol., 31, 189.

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