Ординатура / Офтальмология / Английские материалы / Surgical Atlas of Orbital Diseases_Mallajosyula_2009

Langerhans’ cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized bone marrow–derived Langerhans’ cells (LCs) and mature eosinophils. These can be subdivided into three clinico-pathological entities: acute disseminated LCH, unifocal and multifocal unisystem LCH, and multisystem LCH. There are three forms of presentation.

Eosinophilic Granuloma: single organ involvement.

Hand-Schuller-Christian Syndrome: lytic bone lesions, diabetes insipidus and exophthalmos.

Letterer-Siwe disease: severest form of the disease found in infants, involving lesions in the liver, bone marrow, spleen and skin.

Langerhans’ cell histiocytosis (LCH) accounts for less than 1% of all orbital tumours. Orbital involvement in LCH is characterised by osteolytic lesions with sclerotic margins along with soft tissue involvement.

The typical cytopathological picture consists of Langerhans’ cells along with eosinophils and a varying number of neutrophils, lymphocytes, macrophages and multinucleated giant cells with pale ill-defined eosinophilic cytoplasm and lobulated nuclei with longitudinal grooves, best visualized in Papanicolaou-stained smears.1 A definitive diagnosis is made by presence of Birbeck granules on electron microscopy (rod-like structures with a striated core having dilated ends giving a tennis racket appearance) or positivity for CDI antigen determinants on cryostat sections. In an appropriate clinicoradiological setting, a typical pathology alone can be used for effective diagnosis and definite proof of LCH.2

Management modalities vary from observation, curettage, intralesional steroids, low-dose radiation, high-dose systemic corticosteroids and chemotherapy, bone marrow transplantation and antibody therapy for recalcitrant cases. The most effective treatment is chemotherapy with Vincristine, Vinblastine, Etoposide and steroids. Low dose radiation in 4-6 fractions may be used when the disease is extensive, inaccessible or if it threatens an important organ.3

1.Ayala AG, RO-JY, Famming CV, Flores JP, Yaskee AW. Core needle biopsy and fine needle aspiration in diagnosis of bone and soft tissue lesions. Hematol Oncol Clin North Am Jun 1995; 9:633-51.

2.Pohar-Marinsek Z, Us-Krasovec M. Cytology of Langrehans cell histiocytosis. Acta Cytol 1996; 40:1257-64.

3.Sessa S, Sommelet D, Lascombes P, Prevol J. Treatment of Langerhans cell histiocytosis in children - Experience at the children’s Hospital of Nancy. J Bone Joint Surgery-Am 1994; 76:1513-25.

ROSAI-DORFMAN DISEASE

Synonyms: Sinus Histiocytosis with Massive Lymphadenopathy, Destombes Rosai-Dorfman disease.

Sinus Histiocytosis with Massive Lymphadenopathy (SHML) otherwise known as Rosai Dorfman Disease, (RDD), is a rare, benign systemic, idiopathic reactive proliferation of distinctive histiocytes, characterised by massive lymphadenopathy, particularly in the head and neck region, and often associated with extra nodal involvement. The orbit is a common extranodal site of RDD.1

Widespread dissemination with liver, kidney, respiratory organs, orbit, and eyeball involvement has been reported rarely. Lymphoproliferation in the soft tissues of the orbit and in the lids has been reported in 12% of cases but intraocular involvement is rare.

The histologic hallmark of sinus histiocytosis with massive lymphadenopathy (SHML) are large intrasinusoidal cells exhibiting cytophagocytosis. Microscopic examination of the lymph nodes shows a polymorphous infiltrate composed of plasma cells, neutrophils, lymphocytes, and histiocytes. The histiocytes often contain phagocytised lymphocytes, a histological finding termed emperipolesis. An immunohistochemical staining panel that includes CD31 and S100 facilitates the diagnosis of SHML.2

Most effective regimen is a vinca alkaloid combined with an alkylating agent and a corticosteroid. The most commonly used regimen is a combination of cyclophosphamide, vincristine, mercaptopurine, and prednisolone. Treatment causes regression of the tumor and resolution of

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lymphadenopathy with minimal recurrence. Surgery is indicated rarely, in life or function threatening situations.

REFERENCES

1.Friendly DS, Font RL, Rao NA. Orbital involvement in ‘sinus’ histiocytosis. Arch Ophthalmol 1977;95:2006–11.

2.Slone SP, Fleming DR, Buchino JJ. Arch Pathol Lab Med 2003 Mar;127(3):341-4.

ORBITAL XANTHOGRANULOMA

Adult xanthogranulomatous diseases are nonLangerhans histiocytic disorders (type II) involving the ocular or orbital tissues and constitute a group of entities with varying manifestations. They are adult onset xanthogranuloma (AOX), which is isolated with no systemic associations, adult onset asthma with periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX) and ErdheimChester disease (ECD). Juvenile xanthogranulomas usually present with skin or intraocular lesions and orbital involvement which is rare, occurs almost exclusively in children.1

Ocular involvement maybe in the form of eyelid or orbital mass, proptosis, orbital bone mass and extraocular muscle involvement,epibulbar mass, uveal mass, uveitis and rarely retinal and choroidal involvement. While the orbit or adnexal xanthogranuloma tends to be anterior in AOX, AAPOX, and NBX, it is often diffuse in ECD and leads to visual loss.

Diagnosis is confirmed by biopsy. The characteristic appearance of xanthogranulomas on histopathology is proliferation of histiocytes, plasma cells and lymphocytes with Touton giant cells that stain positive for lipid. Touton giant cells are multinucleate cells with the nuclei arranged in a wreath around a nidus of eosinophilic cytoplasm and separated from the cell membrane by a rim of translucent foamy cytoplasm.2 Necrosis (necrobiosis) with pallisading epitheliod histiocytes is mostly seen in NBX whereas large lymphoid aggregates with germinal centers are often found in cases of AAPOX. ECD exhibits florid fibrosis with fewer follicles and more dispersed lymphocytes and lipid laden histiocytes.

The clinical course is chronic and often progressive. Various treatment modalities include local excision, periocular and systemic steroids, chemotherapy with low dose chlorambucil, nitrogen mustard, cyclophosphamide, melphalan, local radiation and plasma exchange.

REFERENCES

1.Zelger B, Cerio R, Orchard G, et al. Juvenile and adult xanthogranuloma. A histological and immunohistochemical comparison. Am J Surg Pathol 1994;18:126–35.

2.Murthy R, Honavar SG, Vemuganti GK, Naik M, Burman S. Isolated giant xanthogranuloma of the orbit. Indian J Ophthalmol [serial online] 2007 [cited 2007 Jul 22]; 55: 156-58.

CASE ILLUSTRATIONS

Case 1

An 18-year-old female, presented with recurrent swelling of the right upper lid of 4 months duration.There was no history of pain, redness, diplopia or defective vision. A cystic mass was excised elsewhere 8 months back, histopathology reports were not available.

On examination, best corrected visual acuity in both eyes was 6/6,N6. Ocular movements were full and painless.There was fullness of the upper temporal part of the right orbit. A firm to hard cord like mass was felt preseptally. The mass was adherent to the bone at the lateral canthus. (Figure 8.3) There was no lymphadenopathy.

CT scan (Figure 8.4) showed enlarged mass, not separate from lacrimal gland, surrounding the globe. It was heterogenous in density.

Figure 8.3: Showing fullness of upper temporal part of the right orbit in a patient with sarcoidosis

Figure 8.4: CT scan showing anteriorly located heterogenous mass in the upper temporal quadrant in patient with sarcoidosis

Total excision of the mass was performed through anterior orbitotomy.Intraoperatively the mass was found to be arising from the palpebral part of the lacrimal gland.

Histopathological examination revealed chronic granulomatous inflammation with no evidence of caseation. Large amounts of granuloma with epitheloid cells and giant cells were observed, suggestive of sarcoidosis (Figure 8.5).

Special stain for fungus and acid fast bacilli were negative.

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Blood tests for serum calcium, phosphorus, proteins, angiotensin converting enzyme and serum lysozyme were within normal limits.

No systemic medications were started in view of normal blood investigations.

The patient was asymptomatic and there was no recurrence during the postoperative follow up of two years.

Case 2

A male farmer, 45 years of age, presented with complaints of protrusion of right eyeball for the past 2 months. His general health was good. Previous thyroid profile was normal.

Examination revealed best corrected visual acuity of 6/6p, N6 and 6/5, N6 in the right and left eyes respectively. There was periocular fullness and inferior scleral show of 2 mm.The globe was pushed forwards by 9 mm,outwards by 3 mm and upwards by 2 mm. Ocular motility was normal. There was no relative afferent papillary defect.There was increased resistance to retropulsion (Figure 8.6). A firm mass was palpable in the inferomedial orbit, posterior extent of which could not be felt.

Slit lamp examination of the anterior segment and intraocular pressure were within normal limits.Fundus examination revealed disc edema with no choroidal folds. CT scan revealed an illdefined heterogenous mass lesion in the right inferomedial orbit extending upto the apex.Medial rectus and inferior rectus were included in the mass lesion (Figures 8.7 and 8.8). We did a right orbital biopsy through a subciliary incision, with debulking of the tumor under general anesthesia. Intraoperatively an infiltrating grey white firm mass was seen, which

Figure 8.5: Photomicrograph showing non-caeseating granulomas (Hematoxylin Eosin x 200)

Figure 8.6: Photograph showing periocular fullness, proptosis and scleral show in a patient with nonspecific inflammation of right orbit

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Figure 8.7: Axial CT scan showing illdefined heterogenous mass lesion extending upto apex in a patient with nonspecific inflammation

Figure 8.8: Coronal CT scan - Medial rectus and Inferior rectus muscles involvement in the nonspecific inflammation of orbit

was difficult to cut and hence was removed piecemeal. Histopathological examination of the specimen was consistent with a diagnosis of non specific inflammation with extensive fibrocollagenous tissue. In view of this finding,ultrasound abdomen was done to rule out retroperitoneal fibrosis. ANCA test was advised to rule out Wegener’s granulomatosis. Both test reports were found to be within normal limits. Patient was started on tapering dose of oral steroids, starting with prednisolone 50 mg/day, reducing it by 10 mg every 3 days and tab pentoxyfylline 400 mg TDS for one month

followed by 400 mg BD for one month. There was significant clinical improvement postoperatively with vision improving to 6/6, and complete resolution of proptosis.

Case 3

A young female aged 15 years, presented with small swelling in the upper outer quadrant of the left eye since 2 years. The swelling was progressively increasing in size. There was no pain, visual disturbance or diplopia.

On examination, fullness of superotemporal region with displacement of the globe downwards and medially was seen (Figure 8.9). A soft to firm swelling with illdefined margins was palpable. It was compressible, non reducible, non pulsatile and non tender. There was increased resistance to retropulsion. There was no lymphadenopathy. CT scan revealed well defined, heterogeneously dense, non enhancing enlargement of lacrimal gland. (Figures 8.10A and B). We excised the mass in toto through lateral orbitotomy. Histopathology examination revealed focal collection of chronic inflammatory cells with abundant fibrocollagenous tissue suggestive of nonspecific inflammation of lacrimal gland (Figure 8.11). Postoperatively, patient was symptom free on follow up of 5 years.

Case 4

A 32-year-old female presented with complaints of protrusion, pain and redness in the right eye associated with progressive dimunition in vision since 1 year.

On examination, the best corrected visual acuity in right eye was 2/60, N36. Marked lid edema and

Figure 8.9: Photograph showing fullness of superotemporal region with downward displacement of the right globe in a patient with nonspecific inflammation of lacrimal gland

Figure 8.11: Photomicrograph showing specimen of lacrimal gland with chronic inflammatory cells surrounding it, suggestive of inflammation of lacrimal gland (Hematoxylin Eosin x 100)

conjunctival congestion was seen, globe was displaced forwards and downwards. Elevation and abduction of the globe was restricted. A palpable mass was felt in the superotemporal quadrant. Preauricular and submandibular lymphadenopathy was present on the same side. Ultrasound abdomen was normal, FNAC showed reactive changes with mild eosinophilia. CT scan showed large extraconal orbital mass surrounding the globe all round, infiltrating the periocular structures (Figure 8.12). We

Figure 8.12: CT scan showing large extraconal orbital mass surrounding the globe and infiltrating the periocular structures in a patient with Kimura's disease

performed a lateral orbitotomy. Intraoperatively, the mass was firm in consistency and was extensively infiltrating the periorbital, lateral orbital and the lacrimal gland region extending upto the apex.

Histopathological report confirmed the diagnosis of angiolymphoid hyperplasia with eosinophilia

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(Kimura’s disease) (Figure 8.13). A course of systemic steroids was given. Visual acuity improved to 6/6, N6 in the affected eye. She came back 4 months later with severe pain and headache, with massive proptosis and keratinization of conjunctiva and cornea. Right eye had no perception of light. Patient was referred to oncologist for chemotherapy and radiotherapy. The response was not satisfactory. In view of the above, exenteration of the right orbit was done. (Figure 8.14) Patient was fitted with a spectacle mounted prosthesis. Recurrence was seen the form of tiny nodular subcutaneous lesions. CT scan evidence of orbital recurrence was seen in the form of soft tissue filling orbit (Figure 8.15). As the lesion was non malignant, it was decided to watch the lesion for 6 months. Patient thereafter was lost

Figure 8.13: CT scan post exenteration of the patient with Kimura's disease

Figure 8.15: Photomicrograph showing blood vessels with scattered eosinophils and lymphocytes in a patient with Kimura's disease (Hematoxylin Eosin x 200)

to follow up. This case shows that some of the benign orbital inflammations may be very aggressive and severe disease may even necessitate orbital exenteration.

Case 5

A male aged 41 years, presented with recurrent left cheek swelling with protrusion of left eye since 5 months. He had undergone partial maxillectomy surgery of the left side 1 year back.

On examination, his best corrected vision was 6/9, N6 in both the eyes.Left proptosis with upward displacement of the globe was seen. A firm to hard swelling was palpable in the left inferior orbit and cheek area. Elevation and depression of the left eye was restricted. (Figure 8.16 ).No afferent papillary defect was present. CT scan revealed soft tissue

Figure 8.14: Appearance following orbital exenteration for severe Kimura's disease

Figure 8.16: Photograph showing left proptosis, upward displacement of globe and fullness in periocular area in a patient with Wegener's Granulomatosis

lesion in the left maxillary sinus with extraconal extension into the orbit (Figures 8.17A and B). The CT scans showed evidence of partial resolution of findings following treatment with oral steroids (Figures 8.18A and B).

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Histopathological examination showed deposits of fibrocollagenous tissue with areas of necrosis with vessel obstruction and dense collection of chronic inflammatory cells (Figure 8.19). A diagnosis of Wegener’s granulomatosis was kept in mind. Chest

X-ray was normal. p ANCA and c ANCA were borderline.Patient was evaluated by rheumatologist and based on clinical diagnosis of Wegener’s granulomatosis, was started on oral steroids. Patient had resolution of symptoms and decrease in swelling following treatment.

Case 6

A male child aged 4 years was referred with CT scan of orbit as a case of malignant lacrimal gland tumor. He had painful swelling of right upper lid of 2 months duration and raised ESR. On examination, his best corrected vision was 6/18 in the right eye. Tender

Figure 8.20: Photograph showing swelling of the lateral part of right upper eyelid in a patient with Langerhans’ cell histiocytosis

swelling of the right upper lid, more on lateral aspect was noticed (Figure 8.20). There was no proptosis. Ocular motility was normal.Rest of anterior segment and fundus examination was normal. CT scan (Figures 8.21A and B) revealed an irregular heterodense mass in the lacrimal gland region, associated with lysis of lateral wall and temporal part of roof of orbit. With the presumptive diagnosis of Langerhan cell histiocytosis, he underwent a complete evaluation including bone marrow which was normal. Chest X-ray revealed interstitial pneumonia. An anterior orbitotomy revealed yellowish black material. Impression cytology and permanent sections confirmed the diagnosis of Langerhans cell histiocytosis. On pediatrician’s advise, patient was started on oral prednisolone and 6-Mercaptopurine. Patient has been free of symptoms on a followup of 3 years.

Case 7

A male child aged 2 years presented with gradual onset of swelling in the right upper lid since 3 months.There was sudden increase in swelling in the last 2 days. On examination, a well circumscribed, non tender, firm lesion was palpable in the superior orbit.Posterior limit could not be felt (Figure 8.22). CT scan showed heterogenous soft tissue in the

Case 8

A 31-year-old female, presented with recurrent episodes of swelling and prominence of left eye since 8 months.She had been on steroids off and on. On examination, fullness of left side of face was seen. There was 4mm left axial proptosis. Firm irregular mass was palpable in the left inferior orbit.There was no lymphadenopathy (Figure 8.25). MRI scan showed a huge fusiform retrobulbar mass (Figures 8.26A to D). Histopathological and immunochemistry study of the biopsy specimen revealed features consistent

A

Figure 8.25: Photographs showing left proptosis, upward globe displacement and fullness of the left side of the face in a patient with

Rosai-Dorfman disease

B