J Clin Pathol: first published as 10.1136/jcp.35.6.606 on 1 June 1982. Downloaded from

J Cliii Pathol 1982;35:606-610

Villous atrophy with crypt hyperplasia in malignant histiocytosis of the nose

K AOZASA

Fronm Osaka University, Faculty oJ Medicine, Departmentt of Pathology, Osaka, Japanl

SUMMARY Intestinal changes, mainly in the jejunum, were investigated in 13 cases of malignant histiocytosis at necropsy and who had presented as lethal midline granuloma.Villous atrophy with crypt hyperplasia was observed in all cases, and a proliferation of atypical histiocytes was observed in seven cases. In the remaining cases, histiocytes with normal morphology increased in number. These findings showed that a prolonged abnormal proliferation of histiocytes was present in the smnall intestine of these cases concurrently with the nasal lesions.

The term malignant histiocytosis was introduced by from the jejunum were available in all cases. In one Rappaport, for "a systemic, progressive, and case, material from the jejunum was also obtained invasive proliferation of morphologically atypical at operation. Adequate clinical data were available histiocytes and their precursors".' Malignant histio- in II cases. cytosis of the intestine has been described in con- nection with malabsorption and ulcerative jejunitis.2 Results In these cases, peroral jejunal biopsy and surgical resection specimens showed villous atrophy with CLINICAL FINDtNGS crypt hyperplasia even in the jejunum remote from The 13 cases showed progressive and destructive areas of ulceration or frank lymphoma. Villous lesions in the nose and adjacent structures, which atrophy with crypt hyperplasia was suggested as a presented as clinical lethal midline granuloma. Nasal http://jcp.bmj.com/ prolonged cryptic phase of malignant histiocytosis. obstruction and discharge were most common Six cases with malignant histiocytosis presenting symptoms with prodromal periods ranging from 2 as lethal midline granuloma have been reported by to 15 months. The clinical courses were rapid and US.3 These patients usually complained of nasal survivals ranged from 0 3 to 40 months (mean 13 obstruction and discharge, fever, and other months). Subcutaneous nodules were noticed in five symptoms restricted to the face. Abdominal symp- cases terminally. Nine patients suffered from toms including malabsorption were not noticed at abdominal symptoms (Table l) terminally, and the the initial presentation. Physical examinations duration of these from the onset to death were two on October 1, 2021 by guest. Protected copyright. revealed ulcerative and granulomatous lesions in the days to 2-5 months (mean 0-8 months). No patient nasal cavity. Deterioration in these patients pro- had diarrhoea or steatorrhoea. gressed rapidly, and mean survival was 13 months. In two cases, multiple ulcers with perforations were PATHOLOGICAL FINDINGS found in the intestine at necropsy and the lesions Multiple ulcers in the gastrointestinal tract were were due to the infiltration of atypical histiocytes. found in four cases at necropsy, and perforation of In this paper, changes in the jejunum are described the jejunum occurred in one case. Perforations of in 13 cases with malignant histiocytosis presenting stomach or jejunum were operatively resected in as lethal midline granuloma examined at necropsy. two cases. The histological examinations of these lesions showed infiltration of atypical histiocytes in Material and methods five cases. Pathological findings in thejejunum in 13 necropsy The 13 cases presented here were examined between cases are shown in Table 2. Villous atrophy and 1958 and 1980. They showed typical histopatho- crypt hyperplasia was observed in all. In seven cases logical findings of malignant histiocytosis. Sections there was a proliferation of atypical histiocytes (Figs. 1, 2). Phagocytosis was not uncommon among Accepted for publicatioii 23 March 1981 the atypical histiocytes (Fig. 3). The proliferation of 606 J Clin Pathol: first published as 10.1136/jcp.35.6.606 on 1 June 1982. Downloaded from

Villous atrophy with crypt hyperplasia in malignant histiocytosis of the nose 'o60%7 Table I Clinical data of thirteen cases

Case Age Sex Abdominal synmptoms Operation Survival (months) l 32 M No No 0 3 2 45 M Abdominal pain No 4 3 32 F Tarry stool No 5 4 57 M No No 6 5 37 M Abdominal pain Gastrectomy for perforation 6 6 44 M Abdominal distension, Haematemesis No 6 7 50 F Abdominal distension No 8 8 22 M Abdominal pain No 13 9 41 F Abdominal pain No 16 10 21 F No No 19 11 36 F Abdominal distension No 21 12 26 M Abdominal pain, Haematemesis Ileojejunotomy for perforation 24 13 49 M No No 40

Table 2 Pathological findings ofjejunum in 13 necropsy atypical histiocytes was usually accompanied with cases lymphoplasmacytic infiltration. Eosinophils were Case Marroscopical findings Microscopical findings uncommon. Grossly visible tumour masses were found in four cases (cases 2, 7, 8, 12) and in these VA CH PAH LPI villous atrophy with crypt hyperplasia was observed I Submucosal bleeding + - + even in intestine remote from the lesions. In cases 2 No . without proliferation of atypical histiocytes, 3 No 4 No histiocytes with normal morphology were increased 5 No in number in the layers beneath the muscularis 6 No 7 Submucosal bleeding mucosae. 8 Multiple ulcers with perforation Necropsy findings in other organs were systemic 9 No and invasive proliferation of atypical histiocytes 10 NA II NA without tumour formation. Multinucleated atypical 12 Multiple ulcers histiocytes were occasionally found. Phagocytosis 13 No - - with variable frequencies was observed in all cases. VACH = villous atrophy with crypt hyperplasia. Lymph nodes were diffusely permeated by atypical PAH = proliferation of atypical histiocytes. and main- http://jcp.bmj.com/ LPI =lymphoplasmacytic infiltration. histiocytes, but redidual lymph follicles NA - not available. tenance of sinus structures were common. In the on October 1, 2021 by guest. Protected copyright.

Fig. 1 Villous atrophy with crypt hyperplasia and lymphoplasmacytic infiltration in the lamina propria. Infiltration ofatypical histiocytes can not be observed. Haematoxylin and eosin x 130.

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608 Aozasa

Fig. 2 Villous atrophy wit/ crypt hyperplasia and infiltration of atypical histiocytes. Lynmphocytes and plasma cells also infiltrated in the lamina propria. Haematoxylin and eosin x 130.

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Fig. 3 Detail of infiltrates underlying the ulcer. Erythrophagocytosis is noted in the centre (arrow). Haematoxylin and eosin, original magnification x 700. J Clin Pathol: first published as 10.1136/jcp.35.6.606 on 1 June 1982. Downloaded from

Villous atrophy with crypt hyperplasia in malignant histiocytosis of the nose 609

Fig. 4 Intrasinusoidal infiltration in the liver. Phagocytosis is noted in the centre. Haematoxylin and eosin x 800.

livers, intrasinusoidal infiltrations were marked for cryptic phase of malignant histiocytosis. (Fig. 4). In the spleen, the infiltration was mainly Malignant histiocytosis presentingas lethal midline found in the red pulp. granuloma has been reported by US.3 These cases showed prodromal symptoms for 2 to 15 months. Discussion Nasal obstruction and discharge were frequently found but abdominal symptoms were never observed Patients with malignant histiocytosis usually show at the initial stage. Abdominal symptoms were pre- fever, lymphadenopathy, general fatigue, and sent terminally in each case. Necropsy revealed a http://jcp.bmj.com/ malaise.4 Common physical findings are a high systemic proliferation of atypical histiocytes, and in- temperature, localised or generalised lymphadeno- testines were involved in five of six cases. It was sug- pathy and hepatosplenomegaly. Malignant histio- gested that this disease had been previously included cytosis with abdominal symptoms occurs, and in the midline malignant reticulosis.10 necropsy may reveal tumour masses in the The 13 cases described here are malignant intestines.5-7 Greenberg et al reported that frequency histocytosis presenting as lethal midline granuloma,

of abdominal symptoms in 146 cases with malignant and abdominal symptoms were present terminally on October 1, 2021 by guest. Protected copyright. histiocytosis was 15%.8 in nine cases. This ratio is much higher than that Isaacson and Wright described a relation between reported by Greenberg et al (15%).8Malabsorption malignant histiocytosis, malabsorption and ulcerative was not found but histological examination of the jejunitis.2 9 The patients suffered from abdominal jejunum revealed villous atrophy with crypt hyper- pain and malabsorption followed by intestinal plasia, with the proliferation of atypical or normal obstruction or perforation. Although the disease histiocytes. Atypical histiocytic proliferation was usually progressed rapidly, a case with prolonged found in 7 (54%) of our cases, which is higher than history of malabsorption was described. Macro- that reported by Warnke et al (33%).4 Lympho- scopically, non-indurated ulcers or tumour masses plasmacytic infiltration was also a constant finding. were observed in the intestines. Microscopically, Although the lesions in the face stand out clinically villous atrophy with crypt hyperplasia was observed in our cases in the initial stages, the presence of even in the uninvolved mucosa. They regarded this villous atrophy suggest that the face and small as a histological feature of a prolonged cryptic phase intestine were simultaneously involved by a systemic of malignant histiocytosis in the intestine. Malab- histiocytosis. sorption and ulcerative jejunitis were observed in Radiotherapy has been suggested for the treatment this phase. Malignant histiocytosis in a preneoplastic of midline malignant reticulosis.11 12 Eichel et al1' or in neoplastic stage accompanied by a host in- reported a good prognosis of midline malignant flammatory reaction was invoked as the explanation reticulosis treated by radiation and nine stage 1 J Clin Pathol: first published as 10.1136/jcp.35.6.606 on 1 June 1982. Downloaded from

610 Aozasa cases all survived 5 yrs. However, Fu and Perzin pathologic study of 29 cases. Cancer 1975;35:215-30. and all their 5 Chawla SK, Lopresti PA, Burdman D, Sileo A, Govoni reported a poor response to radiation AF, Smulewicz JJ. Diffuse small bowel involvement in followed cases died due to tumour.13 In malignant malignant histiocytosis. Am J Gastroenterol 1975;63: histiocytosis improved progress has been reported 129-34. after intensive systemic combination chemo- 6 Macgillivray JB, Duthie JS. Malignant histiocytosis When apparently only the facial area is (histiocytic medullary reticulosis) with spindle cell therapy.14 differentiation and tumour formation. J C/in Pathol involved midline malignant reticulosis and malignant 1977;39:120-5. histiocytosis may be indistinguishable. Since our Marshall AHE, Revell PA. Malignant histiocytosis with investigations suggest simultaneous involvement of associated "reticulum cell sarcoma". J Pathol 1977;122: the face and small intestine in malignant histio- 9-12. 8 Greenberg E, Cohen DM, Pearse G, Kyle RA. Histiocytic cytosis presenting as lethal midline granuloma, we medullary reticulosis. Proc Mayo Clin 1962;37:271-83. recommend that combination chemotherapy and 9 Isaacson P, Wright DH. Intestinal lymphoma associated radiation be preferred to radiation alone in the with malabsorption. Lancet 1978 ;i :67-70. treatment of midline malignant reticulosis or 10 Kassel SH, Echevaria RA, Guzzo FP. Midline malignant reticulosis (so-called lethal midline granuloma). Cancer malignant histiocytosis. 1969 ;23:920-35. Eichel BS, Harrison EG, Jr, Devine KD, Scanlon PW, The author thanks Professor K Matsumoto for Brown HA. Primary lymphoma of the nose including a reviewing the manuscript. relationship to lethal midline granuloma. Anm J Siurg 1966;112:597-605. 2 Fechner RE, Lamppin DW. Midline malignant reticulosis. References A clinicopathologic entity. Arch OtolarYngol 1972 ;95: 467-76. Rappaport H. Tumours of the haematopoietic system. 13 Fu Y-S, Perzin KH. Non-epithelial tumours of the nasal Atlas of tumoutr pathology Washington DC: AFIP. cavity, paranasal sinuses and nasopharynx. Cancer 1979: 1966 :48-63. 43:611-21. 2 Isaacson P, Wright DH. Malignant histiocytosis of the Zuker JM, Carillaux KM, Vanel D, Gerald-Marchant R. intestine: its relationship to malabsorption and ulcerative Malignant histiocytosis in childhood. Clinical study and jejunitis. Hum Pathol 1978 ;9:661-77. therapeutic results in 22 cases. Cancer 1980;45:2821-9. 3 Aozasa K, Watanabe Y, Ikeda H. Malignant histiocytosis presenting as lethal midline granuloma. Pathol Re.s Pract 1981;171:314-24. Requests for reprints to: Dr K Aozasa, Osaka University, 4 Warnke RA, Kim H, Dorfman RF. Malignant histio- Faculty of Medicine, Department of Pathology, cytosis (histiocytic medullary reticulosis)-clinico- Nakanoshima 4-chome 3-57, Kita-Ku, Osaka, 530 Japan. http://jcp.bmj.com/ on October 1, 2021 by guest. Protected copyright.