Case Review
Volume 5, No.1
April 2001
 Abdulrahman H Al-Anazi(1)  Ahmed Ammar(1)
 Bassem Sheikh(1)
 Samar S Barayan(2)
 Fatma Al Mulhim(3)
 (1) Department of Neurosurgery
 (2) Department of Pathology
 (3) Department of Radiology
 King Fahd University Hospital
 Al Khobar
 Saudi Arabia
 Correspondence:
 Dr. Abdulrahman Al-Anazi
 King Fahd Univ. Hospital
 PO Box 40010
 Al Khobar
 Saudi Arabia
 Fax: (966 3) 899 2632
 E-mail: alanazi1@hotmail.com 
Primary Langerhan's cell histiocytosis of the brain - Case report and literature review

ABSTRACT


Primary Langerhan's cell histiocytosis of the brain is considered to be rare and with good prognosis. However, several cases in the recent literature proved that the disease is not particularly rare and frequently fatal. We are reporting a case of primary Langerhan's cell histiocytosis of the brain, which caused the death of a 39-year-old Saudi male patient. The tumour was excised totally twice and radiotherapy was given but in spite of that the patient’s clinical status deteriorated rapidly and death occurred within 6 months. We found 14 other cases in the literature, 5 of the cases ended in death. Therefore, we report this case to draw attention to the fact that this disease is not rare nor benign as previously thought.

Keywords: Cerebral hemisphere and Langerhan's cell histiocytosis

INTRODUCTION

Primary Langerhan's cell histiocytosis (LCH) of the central nervous system is uncommon. When it does occur it usually involves the hypothalamus and pituitary gland.2,9 Rarely, it involves the cerebral hemisphere as an isolated lesion when it may be benign and respond to surgical treatment alone, or it may be a very aggressive lesion with a fatal outcome.
Case Report: A 39-year-old male patient presented with a short history of headache and right 6th and 7th nerve palsies. A computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain showed a ring-enhanced lesion on the right fronto-temporal area surrounded by oedema and causing mid-line shift (Fig. 1). This was initially thought to represent a tuberculoma but it progressed on anti-tuberculous therapy. Accordingly, the patient underwent a craniotomy with total excision of the mass, which by histological examination proved to be a primary LCH. A partially necrotic lesion was seen, composed of Langerhan's-type histiocytes with typical, convoluted nuclei and prominent nucleoli surrounded by heavy, chronic, inflammatory cell infiltration (Fig. 2). The Langerhan's-type histiocytes showed diffuse positivity with S-100 immunostain. T-cell-rich inflammatory infiltration was documented by CD3 stain, and L-26 stain demonstrated B cells in the surrounding brain parenchyma. The patient was given a course of radiotherapy (1600 cGy) which was thought to be adequate for primary LCH. Follow-up MRI (Fig. 3) three months later showed recurrence of the lesion and so a repeat craniotomy was performed, when total removal of the lesion was again achieved. The recurrent mass had identical histological features on histological examination to the initial lesion.

The patient did well for one month post-operatively. He then started to have symptoms and signs of increased ICP and repeat CT and MRI scans of the brain showed further recurrence Fig. 4). The patient was treated conservatively but his condition deteriorated. He became drowsy and then comatose and finally died.




Figure 1
Figure 1– Brain MRI study, T1-weighted SE image after IV injection of gadolinium shows a ring enhancing lesion in the right temporal lobe, surrounded by brain oedema and associated with midline shift to the left.


Figure 2
Figure 2– Photomicrograph of paraffin section showing sheets of large histiocytes with pale cytoplasm and convoluted nuclei mixed with areas of necrosis and mononuclear cell infiltrate. H&E, original magnification x 400





Figure 3
Figure 3– Brain MRI study, T1-weighted SE image after IV injection of gadolinium shows a ring-enhancing lesion surrounded by oedema and minimal midline shift to the left


Figure 4
Figure 4– Brain MRI study, T1-weighted SE image after IV injection of gadolinium shows recurrence of lesion involving both anterior horns of the lateral ventricles, brain oedema and midline shift

Table 1 – Cases with non-fatal outcome

No.

Age/Year

Sex

Symptoms

Location of Tumour

Treatment

Follow-up

Reference

1

9

Male

Intracranial Hypertension

Left temporal

Resection Radiation

1.5 years

Sivalingam, et al
1977

2

35

Male

Seizures

Left frontal

Resection

2 years

Cerda, Nicolas, et al
1980

3

14

Male

Intracranial Hypertension

Left temporal

Total resection

2 years

Greenwood, et al
1982

4

30

Male

Seizures

Left fronto-temporal

Resection

9 months

Mascinski, Kleinschmidt, DeMasters,
1985

5

19

Male

Headaches

Left temporal

Resection

16 months

Hammar, et al
1986

6

26

Male

Headaches
Seizures

Left frontal

Resection

5 months

Penar, et al
1987

7

31

Female

Seizures

Left parieto-occipital

Subtotal Resection Radiation

6 months

Eriken, et al
1988

8

7

Male

Seizures

Right frontal

Total resection

2 years

Itol, et al
1992

9

37

Male

Seizures

Right temporal

Gross total excision

6 months

Montine, et al


Table 2– Cases with fatal outcome

No.

Age/Year

Sex

Symptoms

Location of Tumour

Treatment

Follow-up

Reference

1

34

Female

Headaches
Vomiting
Memory

Left temporal
 thalamus

Partial excision

1.5 years

Daniel SE, et al
1985

2

63

Female

Slurred speech
Right hand
weakness

Pituitary gland
Infundibulum
Mid-brain

Conservative

1 year

Breidahl WH, et al
1992

3

39

Female

Left hemiparesis
Amenorrhoea
D.I.

Right parietal 
lobe
Hypothalamus

Radiation

7 years

Breidahl WH, et al
1992

4

6

Male

Headaches
Vomiting
Seizures

Choroid plexus

Partial excision
Radiation
Chemotherapy

2 months

Kim Eun-Young, et al
1995

5

32

Female

Intracranial  
hypertension

Right insula

Total excision
Radiation
Chemotherapy

7 months

Enne Vital, et al
1996
DISCUSSION

Isolated involvement of the CNS by LCH without conspicuous systemic lesions is uncommon and its clinical course varies from a benign course which responds to total surgical excision to a very malignant course, which does not respond to any treatment modality and the patient dies within a few months, as in our case. Langerhan's cell histiocytosis, previously known as histiocytosis X, is diagnosed histologically either by immunohistochemical evidence of CD1a expression or by ultrastructural detection of Birbeck granules in the cytoplasm.1,3 In 1893, Hand reported the involvement of the hypothalamic-posterior pituitary axis as an important manifestation of LCH.10 On CT scan, cerebral lesions are typically hypodense with surrounding oedema and mass effect, which with contrast enhances either uniformly or peripherally. This may be confused radiologically with the diagnosis of tuberculoma, as in our case, or glioma.5,7,8 On MRI the lesion is usually iso- or hypointense relative to brain on T1- and most commonly hyperintense relative to brain on T2-weighted image. The contrast enhancement is variable.6,11

To our knowledge, only 14 cases have been reported. The patients' age ranged from 6-63 years. By reviewing the literature we were able to divide the patients into two groups according to the final outcome. The first group (Table 1) consists of 9 patients resulting in good outcome, the majority were males (ratio 8:1) and the lesion was mostly single involving the cerebral hemisphere. The second group (Table 2) consists of 6 patients including our patient; all of them resulting in death, the majority were females (ratio 4:2) and the lesion was mostly multifocal and affected a critical structure such as the pituitary gland, thalamus, hypothalamus and brain stem. The clinical manifestation is variable. All patients except two had surgical treatment which ranged from partial to total excision, 7 patients had radiotherapy and only two had chemotherapy. Despite the fact that our patients underwent an initial gross total excision, postoperative radiotherapy was administered based on anecdotal reports in the literature. Also, despite aggressive treatment, the lesion recurred within three months. On review of cases in the literature with fatal compared to non-fatal outcome, the role of radiotherapy remains unclear. Based upon our literature review, we can conclude that LCH is not any more considered to be a very rare disease nor does it always carry a good prognosis. It has been noticed that the follow-up period for some of the patients which have been claimed to have good outcome is rather short.4,12,13 The patient’s sex and location of the lesion are the two most important predictors of the final outcome.

REFERENCES

1. Ben-Ezra JM, Koo CH: Langerhan's cell histiocytosis and malignancies of the M-PIRE system. Am J Clin Pathol 1993, 99: 464-471
2. Bernard JD, Aguilar MJ: Localized hypothalamic histiocytosis X. Report of a case. Arch Neurol 1969, 20: 368-372
3. Emile J-F, Wechsler J, Brousse N, Boulland ML, Cologon R, Fraitag S, Voisin M-L, Gaular P, Boumsell K, Zafrani E-S: Langerhan's cell histiocytosis. Definitive diagnosis with the use of monoclonal antibody 010 on routinely paraffin-embedded samples. Am J Surg Pathol 1995, 19: 636-641
4. Eriksen B, Jannis J, Variakojis D, Winter J, Russel E, Marder R, Dal Canto M: Primary histiocytosis X of the parito-occiptal lobe. Hum Pathol 1988, 19: 611-614
5. Geoffray A: Case of the season. Histiocytosis X of the central nervous system. Semin Roentgenol 1984, 9: 257-258
6. George JC, Edwards MK, Smith RR, Provisor AJ: MR of intracranial Langerhan's cell histiocytosis. Case report. J Comput Assist Tomogr 1994, 18(2): 295-297
7. Goldberg R, Han JS, Ganz E, Roessman V: Computed tomography demonstration of multiple parenchymal central nervous system nodules due to histiocytosis X. Surg Neurol 1987, 27: 377-380
8. Greenwood SM, Martin JS, Towfighi J: Unifocal eosinophilic granuloma of the temporal lobe. Surg Neurol 1982, 17: 441-444
9. Kepes JJ, Kepes M: Predominantly cerebral forms of histiocytosis-X. A reappraisal of “Gagel’s hypothalamic granuloma”, “granuloma infiltrates of the hypothalamus” and “Ayala’s disease” with a report of four cases. Acta Neuro Pathol 1969, 14: 77-98
10. Kepes JJ: “Xanthomatous” lesions of the central nervous system: definition, classification and some recent observations. Prog Neuro Pathol 1979, 4: 179-211
11. Kim E-Y, Choi J-U, Kim T-S, Kim D-I, Kin K-Y: Huge Langerhan's cell histiocytosis granuloma of choroid plexus in a child with Hand-Schuller-Christian disease. Case report. J Neurosurg 1985, 83: 1080-1084
12. Montine TJ, Hollensead SC, Ellis WG, Martin JS, Moffat EJ, Burger PC: Solitary eosinoplic granuloma of the temporal lobe: a case report and long-term follow-up of previously reported cases. Clin Neuro Pathol 1994, 13: 225-228
13. Penar PL, Kim JH, Cyatte D: Solitary eosinophilic granuloma of frontal lobe. Neurosurg 1987, 21: 566-568

GENTLE REMINDERS
  Vasogenic Cytotoxic Hydrocephalic
Pathogenesis Increased capillary permeability Cellular swelling-glial, neuronal, endothelial Increased brain fluid due to block of CSF absorption
Location of oedema Chiefly white matter Gray and white matter Chiefly periventricular white matter
Oedema fluid composition Plasma filtrate, including plasma proteins
Increased 		Increased intracellular water and sodium
Decrease 		CSF

Increased
Extracellular fluid volume Increased Normal Normal
Capillary permeability to large molecules (inulin)      
Therapeutic effects Stereoids Beneficial in brain tumour and abscess Not effective (possibly Reye's syndrome) Uncertain effectiveness (possibly pseudotumour
Osmotherapy Acutely reduces volume of normal brain tissue only Acutely reduces brain volume in hypo- osmolality Rarely useful
  Improves compliance Improves compliance Improves compliance
Acetazolamide ?Effect No direct effect Minor usefulness
Furosemide ?Effect No direct effect Minor usefulness
CSF = Cerebrospinal Fluid
 


HOME | UP | FEEDBACK
Historical Notes | Executive Committee| Regional Societies and Links | Forthcoming Meetings
Bylaws | Journal | News and Letters

http://www.panarabneurosurgery.org/
Copyright 2001