The medical guidelines for childhood LCH have been published in Pediatric Blood & Cancer  (PBC), Wiley Online Library.

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Biopsy and Histological Examination

Author(s): Euro Histio Net Work Group for LCH Guidelines (see introduction page), Created: 2011/03/09, last update: 2013/08/28

The diagnosis of LCH should be based on histological and immunophenotypic examination of a biopsy of lesional tissue. Biopsy should be taken from the most accessible organ: skin if involved; while in case of multiple skeletal involvement, the bony lesion that is most easily accessible should be chosen for biopsy. The main diagnostic feature is the morphologic identification of the characteristic LCH cells, but positive staining of the lesional cells with CD1a and/or Langerin (CD207) is required for definitive diagnosis [Chikwava/Jaffe 2004; Lau/Chu/Weiss 2008; Swerdlow et al 2008;Valladeau et al 2000].

Electron microscopy is no longer recommended since it has been shown that the expression of Langerin fully correlates with the presence on electron microscopy of Birbeck granules, which were previously one of the criteria required for definitive diagnosis. There are, however, very few exceptions as the fact that in organs such as liver Birbeck granules are not present and CD1a and/or Langerin may be negative.

When tissue sample is taken from a bone lesion, curettage of the center of the lesion is usually sufficient for pathologic diagnosis and also may trigger the initiation of a healing process. Complete excision of bone lesions is not indicated since it may increase the size of the bony defect and the time to healing; it might also result in permanent skeletal defects.

In very few circumstances, when the only lesion involves particular structures and the risk of biopsy outweighs the need for a definitive diagnosis, the risk/ benefit of biopsy should be carefully considered. This is the case in patients with isolated involvement of a vertebral body without adjacent soft tissue affection, as in case of “vertebra plana” or the isolated involvement of the odontoid peg.

The “vertebra plana” radiologic imaging is due to a lesion in the vertebral bone that leads to collapse of the vertebral body. However, if the decision to skip or postpone a biopsy is met, every effort should be made to consider other clinical conditions that might lead to a similar radiological finding, such as Ewing sarcoma, non Hodgkin lymphoma of the bone, osteomyelitis.

Possible other conditions for manifestations of LCH.

Appropriate additional investigations should be performed in order to exclude other diseases with a great deal of certainty. In particular in case of vertebra plana, a spinal MRI within two weeks is mandatory and a further multidisciplinary work up (including orthopedic surgeon and hemato-oncologist) is preferable in order to exclude a malignant tumor. Patients without histologically confirmed diagnosis need to be carefully monitored by appropriate imaging at least for the next 6 months in order to re-consider the need for biopsy and its justification (e.g. to exclude malignancy). Another possible, but rare situation is that of pituitary deficit (e.g. diabetes insipidus) and/or neurological impairment with a small and not easily accessible lesion on head or spinal MRI. The same approach of close monitoring and re-assessment of the need for biopsy is recommended.

References

[Chikwava/Jaffe 2004] Chikwava K, Jaffe R: Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2004 Nov-Dec; 7: 607 [PMID: 15630529]

[Lau/Chu/Weiss 2008] Lau SK, Chu PG, Weiss LM: Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders. The American journal of surgical pathology 2008, 32: 615 [PMID: 18277880]

[Swerdlow et al 2008] Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Thiele J, Vardiman JW: WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. IARC press, Lyon Fourth Edition. 252, pp.358 [ISBN: 9789283224310

[Valladeau et al 2000] Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, Duvert-Frances V, Vincent C, Schmitt D, Davoust J, Caux C, Lebecque S, Saeland S: Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 2000, 12: 71 [PMID: 10661407]