Vojnosanit Pregl 2013; 70(12): 1159–1161. VOJNOSANITETSKI PREGLED Strana 1159
Correspondence to: Aleksandra Lovrenski, Center for Pathology, Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia. E-mail: [email protected]
C A S E R E P O R T UDC: 616.24-006-033.2 + 616.379-091.8-031
DOI: 10.2298/VSP1312159L
Multisystem Langerhans cell histiocytosis coexisting with
metastasizing adenocarcinoma of the lung: A case report
Multisistemska histiocitoza Langerhansovih
ü
elija udružena sa
metastaziraju
ü
im adenokarcinomom plu
ü
a
Aleksandra Lovrenski*†, Mirna Djuriü†‡, Ištvan Klem*†, Živka Eri*†, Milana Panjkoviü*†, Dragana Tegeltija*†, Djordje Považan†‡
*Center for Pathology, ‡Clinic for General Pulmology, Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia; †Faculty of Medicine, University of Novi Sad,
Novi Sad, Serbia
Abstract
Introduction. Langerhans cell histiocytosis (LCH) is an common disease of unknown etiology characterized by un-controlled proliferation and infiltration of various organs by Langerhans cells. Case report. We presented a 54-year-old man, heavy smoker, with dyspnea, cough, hemoptysis, headache and ataxia, who died shortly after admission to our hospital. On the autopsy, tumor was found in the poste-rior segment of the right upper pulmonary lobe as well as a right-sided occipitoparietal lesion which penetrated into the right ventricle resulting in internal and external hemato-cephalus. Histologically and immunohistohemically, the di-agnosis of primary lung adenocarcinoma with brain metas-tasis was made (tumor cells showed positivity for CK7 and TTF-1 which confirmed the diagnosis). In the lung paren-chyma around the tumor, as well as in brain tissue around the metastatic adenocarcinoma histiocytic lesions were found. Light microscopic examination of the other organs also showed histiocytic lesions involving the pituitary gland, hypothalamus, spleen and mediastinal lymph nodes. Immu-nohistochemical studies revealed CD68, S-100 and CD1a immunoreactivity within the histiocytes upon which the di-agnosis of Langerhans' cells histiocytosis was made. Con-clusion. The multisystem form of LCH with extensive or-gan involvement was an incidental finding, while metastatic lung adenocarcinoma to the brain that led to hematocepha-lus was the cause of death.
Key words:
histiocytosis, langerhans-cell; diagnosis; lung
neoplasms; adenocarcinoma; immunohistochemistry.
Apstrakt
Uvod. Histiocitoza Langerhansovih ýelija je retko obolje-nje nepoznate etiologije koje se karakteriše nekontrolisa-nom proliferacijom i infiltracijom razliÿitih organa Lan-gerhansovim ýelijama. Prikaz bolesnika. Prikazan je bo-lesnik, star 54 godine, teški pušaÿ, sa simptomima dispne-je, kašlja, hemoptizija, glavobolje i ataksije koji je kratko nakon prijema u našu ustanovu egzitirao. Na obdukciji, naĀen je tumor u posteriornom segmentu desnog gornjeg režnja, kao i tumorska masa lokalizovana desno okcipito-parijetalno koja je penetrirala u desnu komoru dovodeýi do unutrašnjeg i spoljašnjeg hematocefalusa. Histološki i imunohistohemijski, postavljena je dijagnoza primarnog pluýnog adenokarcinoma sa metastazom u mozak (tumor-ske ýelije su pokazale pozitivnost za CK7 i TTF-1, što je potvrdilo dijagnozu). U pluýnom parenhimu oko tumora, kao i u moždanom parenhimu oko tumora naĀene su his-tiocitne lezije. Histološka analiza iseÿaka uzetih iz hipofize, hipotalamusa, slezine i medijastinalnih limfnih ÿvorova ot-krila je, takoĀe, prisustvo ovih lezija. Imunohistohemijski, ove lezije pokazale su pozitivnost na CD68, S-100 i CD1a, na osnovu ÿega je i postavljena dijagnoza histiocitoze Lan-gerhansovih ýelija. Zakljuÿak. Multisistemska forma his-tiocitoze Langerhansovih ýelija sa ekstenzivnim zahvata-njem organa je sluÿajan nalaz, dok je hematocefalus izaz-van metastatskim adenokarcinomom bio uzrok smrti kod ovog bolesnika.
Kljuÿne reÿi:
Strana 1160 VOJNOSANITETSKI PREGLED Volumen 70, Broj 12
Lovrenski A, et al. Vojnosanit Pregl 2013; 70(12): 1159–1161.
Introduction
Langerhans cell histiocytosis (LCH) includes diseases previously designated as histiocytosis X, eosinophilic granu-loma, Letterer-Siwe disease, Hand-Schuller-Christian syn-drome and Langerhans cell granulomatosis. This is an common disease of unknown etiology characterized by un-controlled proliferation and infiltration of various organs by Langerhans cells, often organized into granulomas 1. It occurs predominantly in children and young adults, but no age is an exemption. Practically any organ can be involved, but bone and skin are the sites of predilection. Patients are categorized as having single-system disease at a single or multiple sites, or as having multisystem disease. Single-system disease of LCH involves mainly bones or lungs and usually follows a benign course and can regress spontaneously. The clinical presenta-tion of multisystem LCH, which carries a poor prognosis in a number of cases, is highly variable depending on the organs involved, mainly bones, skin, lungs, pituitary glands and less commonly liver, spleen, hematopoietic and central nervous system 1–3. The association of single-system disease with ma-lignant neoplasm is not so rare (particularly in association with malignant lymphoma), but association of multisystem LCH with a malignant neoplasm is rare and, generally, has been the subject of isolated case reports 4. To our knowledge, this is the first case reporting on the association of multisystem LCH with metastasizing adenocarcinoma of the lung.
Case report
A 54-year-old man, heavy smoker (30 years/3 packs a day), was admitted to our hospital for further diagnostic ap-proach to the radiologically detected change in the right lung.
Four months before admission shortness of breath and cough with hemoptysis occured, and a month before admission the patient was refered to the neurologist because of walking in-stability, loss of strength in the left half of the body, and morning headaches. Computerized tomography (CT) scan of the endocranium showed right-sided occipitoparietal lesion, which primarily exhibited characteristics of secondary infil-tration, and CT scan of the thorax showed inhomogeneous, extensive infiltration predominantly localized in the upper lobe. On the fourth day after admission hemoptysis occured, and bronchoscopic examination was performed, but histo-pathological findings did not clarify the etiology of the change. After two days a deterioration in general condition with intense headache developed, and despite all the applied therapeutic measures the patient passed away.
At autopsy, macroscopic examination of the lungs re-vealed an excavated tumor mass 1.8 cm in largest dimension in the posterior segment of the right upper lobe, which histo-pathologically corresponded to adenocarcinoma. In brain pa-renchyma, right-sided occipitoparietal necrotic, and hemor-rhagic lesion 5.7 u 3,8 cm in largest diameter, which pene-trated into the right ventricle resulting in internal and exter-nal hematocephalus, was observed. Histologically and im-munohistohemically, the diagnosis of primary lung adeno-carcinoma with brain metastasis was made (tumor cells showed positivity for CK7 and TTF-1 which confirmed the diagnosis) (Figures 1a and 1b).
Within the tumor, in the lung parenchyma around the tu-mor, as well as in the brain tissue around metastatic adenocar-cinoma, histiocytic lesions were found (Figure 2a). Light mi-croscopic examination of the other organs also showed histio-cytic lesions involving the pituitary gland, spleen, hypothala-mus, and mediastinal lymph nodes (Figures 2b and 2c).
a) b)
Fig. 1 – a) Adenocarcinoma of the lung (HE, u 10); b) Metastatic adenocarcinoma in the brain parenchyma (HE, u 5).
a) b) c)
Volumen 70, Broj 12 VOJNOSANITETSKI PREGLED Strana 1161
Lovrenski A, et al. Vojnosanit Pregl 2013; 70(12): 1159–1161. These histiocytic lesions were made of clusters and sheets of characteristically ovoid cells with abundant, lightly eosinoph-ilic cytoplasm, grooved or contorted nuclei, fine chromatin, a thin nuclear membrane and inconspicuous nucleoli. Multinucleated giant cells were also present. Immunohisto-chemical studies revealed CD68 (histiocytic marker), cytoplas-mic protein S-100 and glycoprotein CD1a (a marker of Langer-hans’ cells) immunoreactivity within the histiocytes upon which the diagnosis of LCH was made (Figures 3a, 3b and 3c).
Discussion
Analysis of a large cohort of Mayo Clinic patients (314 patients between 1946 and 1996) with histologically proven LCH showed that 96 patients had LCH involving multiple systems, 114 had isolated osseous LCH, and remaining 104 had nonosseous single system LCH. Only 27 of 314 patients had coexisting neoplasms. Five patients had lung carcinoma (four adenocarcinoma and one small cell carcinoma), but all of them had pulmonary LCH without involvement of other organs with Langerhans' cells. Four patients had multisystem LCH (mostly affecting bones, skin, lymph nodes and pitui-tary gland) coexisting with breast adenocarcinoma, parathy-roid adenoma, pancreatic cystadenoma and pontine mass 5.
A group of autors at the University of Minnesota re-viewed their own charts as well as reported cases in the lit-erature between 1960 and 1992. Of the 91 patients, 39 had
LCH with malignant lymphoma (25 of these cases were Hodgkin disease), in 22 patients LCH was reported in asso-ciation with leukemia, and in remaining 30 patients LCH was associated with a variety of solid tumors, including lung car-cinoma in 12 patients (nine adenocarcar-cinoma, two large cell carcinoma and one squamous cell carcinoma). In 11 cases of associated lung carcinomas and LCH, the diagnosis of LCH was confined pathologically to the lung 6. In one case re-ported by Hammar et al. 7 LCH affected bone and lung and
this is the only reported case of lung adenocarcinoma coex-isting with LCH which was not limited to the lung. Accord-ing to these two studies, simultaneous association of LCH with lung carcinoma suggest that pulmonary LCH represents a reaction to the tumor.
Conclusion
LCH remains a rare, enigmatic disease which, in most cases, is detected relatively late in its course and which should be included in the differential diagnosis of patients with multisystem disease. In this case, the coexistance of multisystem LCH with extensive organ involvement and metastastic lung adenocarcinoma (that led to hematocephalus and death) represents a coincidental finding, because only in case of a single-system disease one can speak about the re-active nature of LCH.
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Received on May 31, 2012. Accepted on June 26, 2012.
a) b) c)
