Abstract
Eosinophilic granuloma (EG) is a benign bone tumor of unknown origin usually seen in children. It is typically found in flat and long bones of the skull and of the appendicular skeleton, respectively. Small bones are rarely affected. The diagnosis and treatment of EG can be challenging as differential diagnosis includes several disorders that can cause osteolytic lesions. Moreover, surgical treatment can be difficult due to the small size of the bone and surrounding structures. Here we describe a case of EG of the proximal phalanx of the thumb (P1 D1) presenting in a 4-month-old boy with persistent swelling and limited range-of-motion of the interphalangeal joint in the left thumb. Over a 6-year follow-up, no sign of relapse was observed. Moreover, the curetted bone did regenerate, and it appeared homogenously dense as normal trabecular bone on the last plain radiographs; the patient was symptom-free at the last follow-up visit. Clinical presentation, treatment, pathoanatomy, localization, and complication of this form of tumor are discussed, and all previously reported cases are reviewed to give a more comprehensive picture of EG of the hand and fingers.
Keywords: eosinophilic granuloma, hand, finger, phalanx, diagnosis, children
Introduction
Langerhans cell histiocytosis (LCH) consists of a group of histologically similar disorders, characterized by abnormal proliferation of histiocyte-like cells with characteristic Birbeck granules. 1 Letterer–Siwe disease, Hand–Schüller–Christian disease, and eosinophilic granuloma (EG) belong to the same disease entity although clinical presentation varies considerably, ranging from generalized and fulminant to localized and curable.
EG, initially described by Otani and Ehrhch 2 and, subsequently, by Lichtenstein and Jaffe, 3 is one of the mildest forms of the disease, with satisfactory outcome uniformly being reported, especially in children. Although immunitary, inflammatory, and reactive etiology of EG have been investigated, its pathogenesis is still debated. 4 5
The incidence of LCH is estimated to be 3 cases per 1,000,000 children each year. 6 EG predominantly affects children with the highest frequency occurring in patients between 5 and 10 years of age, with a male predominance. 5 7 Seventy percent of all LCH bone lesions are solitary EGs. 4
Any bone is vulnerable to this condition, yet the majority of cases involve flat bones of the skull, mandible, ribs, clavicle, pelvis, and long tubular bones of the extremities; small bones of the extremities are rarely affected. 8 9
The literature counts very few cases of EG of the hand phalanges: several authors report the percentage of phalanx location as <1%, and some cases have been diagnosed in adults. 1 2 5 6 7 8 9 10 11 12 13 14 15 16 17
The primary aim of this report is to present a case of a 4-month-old boy with solitary EG of the proximal phalanx of the thumb (P1 D1) presenting with persistent swelling and limited range of motion of interphalangeal joint of the left thumb. The secondary aim is to give a literature review of EG of the hand and fingers in children.
Case Report
A 4-month-old infant presented at our institution with a 1-month history of ventral swelling and limited range of motion in the left thumb. No fever or lymphadenopathy was recorded.
Examination of the thumb revealed a circumferentially enlarged finger compared with the contralateral side, with a 2 × 2 cm mass present over the proximal phalanx. The overlying skin was intact, with positive inflammatory signs. The interphalangeal joint showed limited passive and active flexion, 20°and 10°, respectively, and full extension. No neurovascular deficits were noted.
Laboratory studies showed a white blood cell count of 7,900 mm 3 , an erythrocyte sedimentation rate (ESR) of 2 mm/h, and a C-reactive protein (CRP) of 0.4 mg/dL. Plain radiographs and computed tomography (CT) scan of the left thumb showed a lytic lesion of the proximal phalanx of the left thumb with swelling of the surrounding soft tissues ( Fig. 1 ). Post-gadolinium T1-weight enhancement and T2-weighted images showed hyperintensity involving the lesion with some extension into the surrounding soft tissues ( Fig. 2 ). Given the history of the patient, we advised open biopsy of the lesion; however, no fine needle aspiration cytology was performed. A lateral surgical approach, centered on the lesion, was implemented. Multiple tumor fragments were removed, and curettage was performed. Complete tumor excision was checked under fluoroscopy control and bone grafting was completed ( Fig. 3 ).
Fig. 1.
Lateral radiograph of the left hand showing osteolytic lesion in the proximal phalanx of the thumb (P2 D1) and swelling in the surrounding soft tissues.
Fig. 2.
Lateral T2-weighted ( A ) and post-gadolinium T1-weighted ( B ) MRI scans showing the involvement of the proximal phalanx of the left thumb (arrow). MRI, magnetic resonance imaging.
Fig. 3.
Postoperative lateral radiograph of the left hand following open biopsy, curettage of the lesion, and bone grafting.
Histopathological examination highlighted proliferation of eosinophils, histiocytes, lymphocytes, and macrophages, as well as aggregates of dendritic Langerhans cells (hematoxylin-eosin staining; low magnification). Moreover, immunohistochemical staining showed positive reaction S-100 protein, CD 68, and CD 1a antibodies ( Fig. 4 ). All these findings confirmed the diagnosis of EG.
Fig. 4.
( A ) Photomicrograph showing proliferation of eosinophils, histiocytes, lymphocytes, and macrophages, as well as aggregates of dendritic Langerhans cells (hematoxylin-eosin staining; low magnification). Moreover, immunohistochemical staining showed positive reaction for S-100 protein ( B ) and CD 68 ( C ) and CD 1a antibodies ( D ) (low magnification).
Following surgery, the patient was immobilized with a soft tissue hand immobilizer for 3 weeks.
Over a 6-year follow-up, no sign of relapse was observed. Moreover, the curetted bone did regenerate, and it appeared as homogenously dense as normal trabecular bone on the last plain radiographs ( Fig. 5 ). The range of motion of the interphalangeal joint of the left thumb has been completely restored (flexion–extension: 85–0°), and the patient has resumed full activities with no pain or swelling in his left thumb ( Fig. 6 ).
Fig. 5.
Lateral ( A ) and anteroposterior radiograph ( B ) of the left thumb at the last follow-up visit.
Fig. 6.
Range of movement of operated left thumb 6 years after index surgery (full flexion–extension).
Literature Review
A search of the Medline database from 1954 to 2018 was performed to identify papers related to EG of the hand. A variety of search terms (“eosinophilic granuloma,” “hand,” “finger,” and “phalanx”) were used, including combinations of index and free-text terms, as recommended in the Cochrane Handbook for Systematic Reviews of Interventions.
Abstracts were screened and relevant full-text articles were retrieved for further review. Reference sections of identified papers were also screened to identify further literature. All levels of evidence were included.
To date, only five cases of EG of the hand, including the present one, have been reported in the scientific literature, 10 11 12 13 and four of these occurred in skeletally immature patients. However, only two cases occurred in infants and were located at the level of the phalanges of the hand, the remaining three being at the level of the metacarpal bone of the hand. The present case is the second and youngest infantile patient with proven diagnosis of EG involving a phalanx of the hand. All cases underwent open biopsy and curettage and showed no sign of recurrence. Table 1 compiles case reports of EG of the hand.
Table 1. Literature review.
| Year | Author | Case number/Age | Location | Treatment | Follow-up | Outcome |
|---|---|---|---|---|---|---|
| 1982 | Jennings et al | 1/Child | Third metacarpal (right) | Biopsy, curettage | N/A | Good, no recurrence |
| 1984 | Palmer | 1/Infant | P1 D3 (left) | Biopsy, curettage | N/A | Good, no recurrence |
| 1993 | Miller and Williams | 1/Adult | Third metacarpal (right) | Biopsy and curettage | 6 months | Good, no recurrence |
| 2003 | Demiral et al | 1/Child | Third metacarpal (right) | Biopsy, curettage | 2 years | Good, no recurrence |
| Present case | 1/Infant | P1 D1 (left) | Biopsy, curettage and bone graft | 6 years | Good, no recurrence | |
Discussion
EGs are relatively uncommon tumors (<1% of bone tumors), and it is extremely rare to find them localized in the bones of the hand. 2 Location at the level of the hand during infancy is particularly unusual. 10 11 12 13 Only two cases of EG involving a phalanx of the hand have been reported ( Table 1 ). Moreover, during the period 2003 to 2018, 36 children, including the present one, with EG of bone were treated and followed up at our institution. Only 5 out of 36 patients had lesions located at the level of the upper extremity (13.9%), and only 1 lesion was located at the level of the hand (present case; 2.8%) ( Table 2 ).
Table 2. Clinical and radiographic data on 34 infants and children with bony Langerhans cell histiocytosis followed at our Institution during the period 2003–2018.
| Case | Gender | Age at diagnosis (y) | Site of lesion (s) | Initial symptoms |
|---|---|---|---|---|
| Abbreviations: F, female; M, male. | ||||
| 1 | F | 1.8 | Humerus | Pain |
| 2 | M | 4 | Spine (L3) | Pain, limping |
| 3 | M | 1.2 | Rib Skull (parietal bone) |
Pain, swelling |
| 4 | M | 1.3 | Spine (C1) Humerus Femur |
Pain, limited activity |
| 5 | M | 2.3 | Spine (T4, L3) | Pain |
| 6 | M | 1.5 | Clavicle | Swelling |
| 7 | M | 10 | Clavicle | Swelling |
| 8 | M | 2.3 | Spine (C4) | Pain, limited activity |
| 9 | M | 4 months | Thumb (P1) | Swelling, limited range of motion |
| 10 | M | 3 months | Spine (L3) | Postural deformity |
| 11 | F | 6 | Spine (T3) | Pain |
| 12 | M | 2 | Tibia | Pain |
| 13 | F | 1.1 | Skull (parietal bone) Humerus |
Pain |
| 14 | M | 4.8 | Spine (C5) | Pain, limited activity |
| 15 | F | 7.8 | Spine (T10) Humerus Pelvis |
Pain |
| 16 | M | 1.6 | Radius | Pain |
| 17 | M | 8 | Spine (T11) | Pain |
| 18 | F | 3.9 | Pelvis | limping, fever |
| 19 | M | 0.7 | Pelvis | Fever |
| 20 | F | 6 | Spine (C3) | Pain, limited activity |
| 21 | M | 4 | Sternum | Pain, swelling |
| 22 | F | 3.7 | Skull (parietal bone) | Pain |
| 23 | M | 1.3 | Spine (C1) | Pain |
| 24 | M | 4 | Skull (parietal bone) Humerus Tibia |
Pain, limited activity |
| 25 | M | 3 | Pelvis | Pain, limping |
| 26 | M | 4 | Spine (T12) | Postural deformity |
| 27 | M | 3 | Spine (L3) | Pain |
| 28 | M | 2 | Scapula | Pain, limited activity |
| 29 | M | 2.8 | Spine (T5,T8) | Pain |
| 30 | M | 6 | Skull (parietal bone) Spine (C3) |
Pain |
| 31 | M | 3.2 | Skull (parietal bone) Pelvis |
Rash, fever |
| 32 | M | 5 | Rib Scapula Sternum Spine (T) |
Postural deformity |
| 33 | F | 2 | Femur | Pain, limping |
| 34 | F | 10 | Pelvis | Pain |
| 35 | M | 1.5 | Spine (C2) | Torticollis |
| 36 | M | 6 | Spine (T6) | Pain |
The pathogenesis of EG is unknown, and various hypotheses have been proposed about its possible etiology. EG is considered by some authors a disorder of the immune system, representing a hypersensitivity reaction to an unknown antigen, with stimulation of the histiocyte–macrophage system. This hypothesis is supported by the fact that the immaturity of the immune system directly influences the severity of the disease. 14 15 EG is considered by other authors a neoplastic process, as clonal proliferation of Langerhans cells and increased expression of several tumor-related factors (wild-type 53,MDM2, p21, p16, Rb, B cell leukemia/lymphoma 2, and transforming GF-A receptor), and the disease’s response to chemotherapeutic drugs have been documented. 16 17 18 19 Moreover, although no specific causal organisms have been identified, an inflammatory origin of the disease has also been suspected due to its self-limiting nature and its response to steroids and antibiotics. 15 20 21
Differential diagnosis includes several disorders that can cause osteolytic lesions, such as Ewing’s sarcoma, osteogenic sarcoma, metastatic tumor, osteomyelitis, Brodie’s abscess, and fibrous dysplasia. However, diagnosis of the lesion is not easily done on plain radiographs alone as EG can be difficult to differentiate from malignant tumors, such as Ewing’s sarcoma, or infection. Moreover, the unusual location of the primary lesion can make diagnosis more difficult, requiring further radiographic examinations such as CT scan, magnetic resonance imaging (MRI), and/or bone scintigraphy. 22
The clinical course of EG of bone is variable. In most patients, EG is a self-limiting process with alternating phases of relapse–remission and spontaneous resolution. Patients with osseous involvement present with pain, swelling, and soft-tissue mass, and local bone pain is the initial symptom in 50 to 90% of the patients with osseous lesions, although it can be difficult to assess in infants. Surgery is indicated in cases of unremitting pain, significant restriction of joint range of motion, aggressive lesion involving the adjacent growth plate, and/or the likelihood of a pathological fracture based on the size and location of the lesion. In particular, surgical curettage, curettage and bone grafting, wide excision, local irradiation, systemic chemotherapy, and intralesional methylprednisolone injection have shown similar success rates. 5 Age of patient, history, presence of symptoms, and single versus multiple localizations are important for making the correct diagnosis. However, a definitive diagnosis can only be made by histological examination. 3 22 The present case was treated with surgery after 1 month of clinical presentation of the disease, as diagnosis was not clear after imaging investigations. Tissue sampling made by open biopsy enabled the diagnosis of EG by showing proliferation of eosinophilic histiocytes as well as positive reaction for S-100 protein and CD 68 and CD 1a antibodies ( Fig. 4 ).
Over a 6-year period, no sign of relapse was observed. Moreover, the curetted bone did regenerate, and it appeared as homogenously dense as normal trabecular bone on the last plain radiographs ( Fig. 5 ). At the last visit, the patient was symptom-free ( Fig. 6 ).
Conclusion
It is unusual for an EG to occur in the hand. In particular, single location at the level of the phalanx is extremely rare. Symptoms depend on tumor location and volume. EG originating in the phalanx can cause loss of finger motion and significant swelling. Due to the rarity of the lesion, its unusual location, and the very young age of the patient, biopsy is needed to make the correct diagnosis.
EG should be considered in the differential diagnosis if clinical examination of the hand or fingers reveals a growing mass, and plain radiographs show signs of osteolysis and bone disruption. As per literature review, a single lesion at the level of the hand usually has a good prognosis and responds well to surgical treatment (curettage and bone grafting), regardless of the anatomical location (metacarpal versus phalanx).
Footnotes
Conflict of Interest None.
References
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