_J Clin Pathol 1995;48:963-965 963 Langerhans' cell : possible

association with malignant germ cell tumour J Clin Pathol: first published as 10.1136/jcp.48.10.963 on 1 October 1995. Downloaded from

W K Ng, K Y Lam, I 0 L Ng

Abstract sometimes occur in association with various A rare case ofadult onset Langerhans' cell types of malignant neoplasms.' Several case histiocytosis associated with dysgermin- reports have been published concerning the oma in a 35 year old Chinese woman is possible association between Langerhans' cell reported. The patient had a history ofdys- histiocytosis and malignant lymphoma, espe- germinoma of left ovary 15 years pre- cially Hodgkin's disease.2" de Camargo et al' viously and had undergone surgery also described the coexistence ofosteosarcoma, followed by radiotherapy and an un- lymphoma, or medulloblastoma and Lan- eventful recovery. She presented again in gerhans' cell histiocytosis in the same patient. March 1994, this time with a left clavicular Malignant germ cell tumour (MGCT) is as- mass, which was shown histologically to be sociated with haematological neoplasia, mainly Langerhans' cell histiocytosis. The report leukaemia.i' However, Langerhans' cell histio- Departnent of illustrates the probable association be- cytosis was not known to associate with Pathology, tween the two lesions, with some dis- MGCT, until a recent case report by Mandel University of Hong et describing a family with clustering of Kong, cussion on the underlying pathogenesis. al,10 Queen Mary (J Clin Pathol 1995;48:963-965) MGCT and Langerhans' cell histiocytosis. We Compound, report a rare case of dysgerminoma and Lan- Pokfulam Road, Keywords: Langerhans' cell histiocytosis, malignant gerhans' cell histiocytosis in a Chinese woman, Hong Kong germ cell tumour. W K Ng which may give some clues to the possible K Y Lam association between the two disease entities. I 0 L Ng Langerhans' cell histiocytosis, previously Correspondence to: Dr W K Ng. known as histiocytosis X, consists of a group Case report Accepted for publication of clinicopathological disorders characterised A 35 year old Chinese woman first presented 13 March 1995 by proliferation of Langerhans' cells. It may in 1979 with a left ovarian mass. Laparotomy revealed a dysgerminoma of the left ovary with metastasis involving the rectal wall. Total ab- http://jcp.bmj.com/ dominal hysterectomy and bilateral sal- pingoophorectomy, together with partial resection ofthe rectum, were performed. There was no clinical evidence of other distant metastases. She was then given postoperative radiotherapy for one year. No adjuvant chemo- therapy was given. on September 28, 2021 by guest. Protected copyright. The postoperative course was uneventful until March 1994 when she noticed pain and swelling over left clavicle for two months. On x ray examination, a 1'5 cm diameter osteolytic lesion was observed in the left clavicle. The clinical diagnosis at that time was metastatic dysgerminoma. Curettage of the lesion was carried out, yielding several small fragments of brownish tissue. The specimen was promptly fixed in 10% neutral formalin and embedded in paraffin wax. Sections, 3 gm thick, were cut and stained with haematoxylin and eosin. The sections were then stained with a polyclonal antibody (diluted 1 in 200; Dako, Copenhagen, Denmark) directed against S- 100 protein using the Streptavidin-biotin complex technique. A representative area was also selected from the paraffin wax block, dewaxed, rehydrated, post- fixed in 1% osmium tetroxide, embedded in epoxy resin, sectioned, and stained with uranyl acetate-lead citrate for subsequent ultra- structural study. Figure 1 Histological section of the left clavicular bony curettage showing Langerhans' cell histiocytosis. Note the characteristic folded nuclei of Langerhans' cells. (Haematoxylin Histological examination ofthe left clavicular and eosin; x 500.) lesion revealed aggregates of ovoid cells ad- 964 Ng, Lam, Ng in the same lymph nodes. One possible ex- planation is that the lymphoma cells may pro- vide a direct or indirect stimulus for the proliferation of these Langerhans' cells. J Clin Pathol: first published as 10.1136/jcp.48.10.963 on 1 October 1995. Downloaded from MGCT, as the name implies, is a malignancy arising from germ cells which may have the potential to differentiate along different lines including yolk sac, trophoblasts and embryonic tissue. Occasional cases of mediastinal, non- seminomatous MGCT associated with haema- tological malignancies have been reported."O Three hypotheses have been put forward67" : (1) leukaemic differentiation of the malignant germ cells; (2) induction of leukaemia by an unknown factor secreted by the germ cell tumour; and (3) the leukaemia and the germ cell tumour may arise independently of each other. In 1989 Chaganti et al8 described a case of mediastinal yolk sac tumour with later leukaemic differentiation, as both tumours showed identical cytogenetic changes. Their results were in agreement with the first hy- pothesis. Mediastinal yolk sac tumour may also be associated with malignant histiocytosis, which may be related to the secretion ofmacro- phage colony stimulating factor or a similar substance by the yolk sac elements.'4 However, there is no previous reported case in the English Figure 2 Electron micrograph of a Langerhans' cell showing characteristic literature mentioning the occurrence of Lan- intracytoplasmic Birbeck's granules in the perinuclear region. Note the barely discernible gerhans' cell histiocytosis and MGCT in the "zip-like" periodic core of the granules with terminal expansion. (Uranyl acetate-lead citrate; x 40 000.) same patient. Our case represents a rare case documenting an occurrence ofadult onset Lan- gerhans' cell histiocytosis 15 years after the diagnosis of dysgerminoma. mixed with small lymphocytes and occasional In 1994 Mandel et all' described a family eosinophils. The ovoid cells had deeply folded with MGCT and Langerhans' cell histiocytosis nuclei with a characteristic "coffee bean" ap- occurring in different family members. The pearance, fine chromatin, inconspicuous nuc- patient with Langerhans' cell histiocytosis leoli, eosinophilic cytoplasm, and ill-defined shared an identical haplotype with her two http://jcp.bmj.com/ cell borders (fig 1). Many of these cells sisters who had a yolk sac tumour and dys- expressed S-100 protein. Ultrastructural germinoma, respectively. Their postulation of examination revealed the presence of in- an association between Langerhans' cell histio- tracytoplasmic Birbeck's granules in the peri- cytosis and MGCT is in agreement with our nuclear region of some of the Langerhans' observation. It is possible that Langerhans' cells (fig 2). The overall features were those of cell histiocytosis, like leukaemia, can share a Langerhans' cell histiocytosis. Bone scan and common stem cell with MGCT; or else the on September 28, 2021 by guest. Protected copyright. skeletal x ray showed no other bony lesions histiocytosis may be the result of stimulation and there was no other evidence of systemic by a "factor" secreted by an occult focus of involvement by Langerhans' cell histiocytosis. residual dysgerminoma. Alternatively, the Lan- The peripheral blood examination was un- gerhans' cell and germ cell proliferations may remarkable. There was no clinical evidence of be triggered by a common stimulus that acts recurrence of dysgerminoma. on both types of cells. The occurrence of the two may also be coincidental. Detailed cyto- genetic and molecular studies in the future Discussion may help to clarify the underlying pathogenic Langerhans' cell histiocytosis is now considered relationship. by some authors to be a probable non-neo- plastic reactive proliferation of Langerhans' 1 Egeler RM, Neglia JP, Puccetti DM, Brennan CA, Nesbit ME. Association of histiocytosis with cells." 12 The nature of the underlying stimuli malignant neoplasms. Cancer 1993;71:865-73. is not known, though immune dysfunction and 2 Kjeldsberg CR, Kim H. as an in- cidental finding in malignant lymphoma. Arch Pathol Lab viral infections have been postulated." The Med 1980;104:37-40. diagnosis of Langerhans' cell histiocytosis is 3 Burns BF, Colby TV, Dorfman RF. Langerhans' cell gran- ulomatosis (histiocytosis X) associated with malignant based mainly on the characteristic cellular lymphomas. Am J Surg Pathol 1983;7:529-33. morphology, appearances on immunohisto- 4 Segal GH, Mesa MV, Fishleder AJ, Stoler MH, Weick JK, Lichtin AE, et al. Precursor Langerhans cell histiocytosis. chemistry, and the ultrastructural identification An unusual histiocytic proliferation in a patient with per- of Birbeck's granules in the cytoplasm. Oc- sistent non-Hodgkin lymphoma and terminal acute mono- cytic leukemia. Cancer 1992;70:547-53. casional cases of Langerhans' cell histiocytosis 5 de Camargo B, Alves AC, Gorender EF, Bianchi A. As- associated with malignant lymphoma, espe- sociation ofmalignancy and Langerhans' cell histiocytosis. Report of three cases. Med Pediatr Oncol 1993;21:451-3. cially Hodgkin's disease, have been 6 DeMent SH, Eggleston JC, Spivak JL. Association between reported,2A mainly coexisting with lymphoma mediastinal germ cell tumors and hematologic malig- Possible association between Langerhans' cell histiocytosis and germ cell tumour 965

nancies. Report of two cases and review of the literature. Rechavi G. Familial clustering of malignant germ cell Am 7 Surg Pathol 1985;9:23-30. tumors and Langerhans' histiocytosis. Cancer 1994;73: 7 Nichols CR, Hoffman R, Einhom LH, Williams SD, 1980-3. Wheeler LA, Gamick MB. Hematologic malignancies 11 Rabkin MS, Wittwer CT, Kjeldsberg CR, Piepkom MW. associated with primary mediastinal germ cell tumors. Ann Flow-cytometric DNA content of histiocytosis X (Lan- J Clin Pathol: first published as 10.1136/jcp.48.10.963 on 1 October 1995. Downloaded from Intern Med 1985;102:603-9. gerhans cell histiocytosis). Am Jf Pathol 1988;131:283-9. 8 Chaganti RS, Ladanyi M, Samaniego F, Offit K, Reuter 12 Van Heerde P, Maarten Egeler R. The cytology of Lan- VE, Jhanwar SC, et al. Leukemic differentiation of a gerhans cell histiocytosis (histiocytosis X). Cywopathology mediastinal germ cell tumor. Genes Chromosom Cancer 1991;2:149-58. 1989;1:83-7. 13 Gordon S. Defense mechanisms. The mononuclear phago- 9 Nichols CR, Roth BJ, Heerema N, Griep J, Tricot G. cyte system. In: McGee JO'D, Isaacson PG, Wright NA, Hematologic neoplasia associated with primary me- eds. Oxford textbook ofpathology. 1st edn. Oxford: Oxford diastinal germ-cell tumors. N Engl J Med 1990;322: University Press, 1992:236-58. 1425-9. 14 Ladanyi M, Roy I. Mediastinal germ cell tumors and histio- 10 Mandel M, Toren A, Kende G, Neuman Y, Kenet G, cytosis. Hum Pathol 1988;19:586-90.

J Clin Pathol 1995;48:965-967 Papillary mucinous adenoma arising in adenomyomatous hyperplasia of the gall bladder

G Y Lauwers, S J Wahl, G V Scott, S J DeRoux

Abstract Methods A case of papillary mucinous adenoma Sections of the gall bladder were fixed in 10% arising in adenomyomatous hyperplasia buffered formalin and embedded in paraffin (AMH) ofthe gall bladder is reported. The wax. Paraffin wax sections 4 gm thick were lesion was unsuspected and discovered by stained with haematoxylin phloxine saffron. routine palpation ofthe gallbladder during Histochemical stains including periodic acid laparotomy. The adenoma developed Schiff (PAS), with and without diastase pre- within fundal AMH and showed cytological treatment, mucicarmine, and alcian blue were atypia. This case illustrates that neoplastic applied to the sections. Sections were also proliferation is indeed possible in AMH stained immunohistochemically with chromo-

and challenges the classical opinion that granin (Boehringer Mannheim, Indianapolis, http://jcp.bmj.com/ AMH is devoid of neoplastic potential. Indiana, USA) monoclonal antibodies using (7 Clin Pathol 1995;48:965-967) the avidin-biotin peroxidase technique, as de- scribed previously.9 Keywords: Gall bladder, cancer, adenomyomatous hyperplasia, adenomyomatosis, mucinous adenoma. Results on September 28, 2021 by guest. Protected copyright. PATHOLOGICAL FINDINGS Adenomyomatous hyperplasia (AMH), also On gross examination, the fundus of the acal- known as adenomyomatosis, is the most fre- culous gall bladder showed a dome shaped, quently diagnosed pseudotumour of the gall 2 x 1-3 x cm. of Florida cystic lesion measuring 1 Micro- University bladder.' Although classically considered to be scopically, the gall bladder mucosa showed College of Medicine, a hyperplastic lesion, recent reports showed Department of normal luminal folds lined by a single layer of Pathology and not only a causative relation between AMH columnar epithelium. The stroma was slightly Laboratory Medicine, and gall bladder carcinoma, but also actual fibrotic and contained lymphocytes in small Gainesville, neoplastic degeneration arising in AMH.2- Florida, USA clusters. AMH was identified within the wall G Y Lauwers Here, we report a unique case of adenomatous of the fundus as the typical multiple ana- G V Scott changes and evidence of neoplastic potential in AMH. stomosing, epithelium lined extrusions ex- Lenox Hill Hospital, tending between bundles of hyperplastic Department of smooth muscle. Foveolar type mucinous meta- Pathology, New York, plasia of the hyperplastic epithelium was also New York, USA Case report present. A large cyst measuring 11 x 5 mm was S J Wahl An 86 year old woman was admitted for surgery observed in continuity with AMH. Its lining S DeRoux J following a diagnosis of adenocarcinoma of the was composed of tall mucinous cells with focal Correspondence to: left colon. A preoperative workup showed no formation of papillae (figs 1 and 2). A large Dr G Y Lauwers, Department of Pathology evidence of metastatic tumour and a left hemi- villous polypoid lesion formed of anastomosing and Laboratory Medicine colectomy was performed. At surgery, pal- fronds protruded into the cystic space. The University of Florida College of Medicine, pation of the gall bladder revealed a small soft fibrovascular stroma of the papillae was in- P.O. Box 100275, mass at the tip of the fundus and a chole- filtrated by lymphocytes and plasma cells. Most Gainesville, Florida 32610, USA. cystectomy was performed. The postoperative of the fronds were lined by a single layer of Accepted for publication course was uneventful and the patient is alive benign mucus cells, although focal cellular tuft- 21 February 1995 and well 17 months after surgery. ing and nuclear atypia were present.