Introduction
The eye is not only an organ of vision but also an index of beauty in the human race.1 The volume of the orbit is small and confined by bony walls on all sides except anteriorly. Within this space is a juxtaposition of numerous structures that subserve visual as well as extraorbital functions.2
The bony orbit is the smallest unit and can be defined as an enclosure bordered by bony structures and a space that contains all tissues and organs that contribute to the function of the eye. Tumors of the orbit arise primarily from soft tissues and bones.3
Tumors of the orbit are rare diseases in ophthalmic pathology-3.5 to 4%.4, 5 All anatomic structures of the orbit can give rise to neoplasm.6 Majority originate between the bony orbital wall and the extraocular muscle cone.7 Orbital tumors are classified into primary and secondary orbital tumors.2 Primary orbital tumors include benign and malignant neoplasms. The direct extension from contiguous anatomical structures, lymphoproliferative disorders, and hematogenous metastasis result in secondary orbital invasion.6 Also the proximity of the paranasal sinuses may lead to the secondary spread of sinus neoplasia and infections or inflammation into the confines of the orbit.3
Most common pediatric tumors are Dermoid cysts, Capillary hemangiomas and Rhabdomyosarcoma.8, 9 Most common adult tumors are Lymphoid tumors, Cavernous hemangiomas and Meningiomas.5, 6 The major presenting symptom is proptosis resulting from the mass effect. Changes in visual acuity or field of vision, diplopia, extraocular motility disturbances or pupillary abnormalities can result from invasion or compression of intraorbital contents secondary to solid tumor. Lid dysfunction and lagophthalmos or lacrimal gland dysfunction can result in exposure keratopathy,keratitis and thinning of cornea.5
Orbital tumors constitute a heterogenous array of lesions and as such pose numerous challenges in terms of diagnosis, imaging and management.10 They call for a closer attention due to its specific anatomic structure and location. Orbital tumors generally require a multidisciplinary approach with cooperation of a number of medical specialities.11
Materials and Methods
The present study is a prospective and retrospective study done between December 2013 to September 2016. All surgically resected specimens of orbital tumors received by Department Of Pathology, Sarojini Devi eye hospital were included. Samples were obtained either through incisional or excisional biopsy. An informed consent was taken from all the study subjects. A total of 54 cases were taken up for the study.
Exclusion criteria
A detailed history taking followed by a detailed ocular examination was done. Routine blood investigations, Xray, MRI and CT scan were done wherever necessary. The lesions were approached as per their anatomical location, size, extent and suspected pathology. The surgically resected specimens were fixed in 10% formalin. Thorough gross examination of each mass for its size, shape and consistency was done.
4-5 sections of 1.2 mm thickness were taken from different areas of the specimen and processed in automatic tissue processor. Blocks were prepared with the help of leuckharts piece. The sections were stained by H&E in all the cases. Immunohistochemistry by different immune markers was done selectively. A histopathological diagnosis thus made was entered in the proforma.
Results
For the period Dec 2013 to Sep 2016: 54 patients with orbital tumors.
Sex ratio: M/F-1.5.
Age ratio: Adult / children – 1.5.
Majority of the patients presented with mass and proptosis.
70.3% cases were benign and 29.6% cases were malignant.
Majority of childhood tumors were dermoid cysts.
6 Out of 54 cases were secondaries.
12 Out of 54 cases were lacrimal gland lesions.
4 Out of 54 cases were meningiomas.
Table 1
Classification of orbital tumors
Table 2
Sex wise distribution of orbital tumors
| S. No. | Sex | Total no. of tumors | No. of benign tumors | No. of malignant tumors |
| 1. | Males | 33(61%) | 21 | 12 |
| 2. | Females | 21 (39%) | 17 | 4 |
| Total | 54 cases | 38 | 16 |
Table 3
Age wise distribution of orbital tumors
| S. No. | Age | Benign Tumors | Malignant Tumors |
| 1. | 1-10 | 11 | 1 |
| 2. | 11-20 | 10 | 2 |
| 3. | 21-30 | 3 | 3 |
| 4. | 31-40 | 4 | 1 |
| 5. | 41-50 | 7 | 4 |
| 6. | 51-60 | 3 | 3 |
| 7. | 61-70 | 0 | 2 |
Table 4
Percentage distribution of clinical features of orbital tumors
| S. No. | Symptoms | Percentage |
| 1. | Swelling | 57.4% |
| 2. | Axial Proptosis | 35% |
| 3. | Eccentric Proptosis | 7.4% |
| 4. | Others | 12.9% |
Table 5
No. of cases based on histopathological diagnosis
Table 6
Percentage distribution of orbital tumors in childhood age group (first and second decades)
| Benign | No. of cases | Malignant | No. of cases |
| Dermoid cyst | 17 | RMS | 2 |
| Capillary hemangioma | 03 | Retinoblastoma orbital extension | 1 |
| Meningioma | 01 | ||
| Total | 21 | Total | 3 |
Table 7
Case distribution of lacrimal gland lesions
| S. No. | Histopathological diagnosis | No. of cases |
| 1. | Lacrimal ductal cyst | 03 |
| 2. | Pleomorphic adenoma | 04 |
| 3. | Adenoid cystic carcinoma | 03 |
| 4. | DLBCL | 02 |
| Total | 12 |
Table 8
Distribution and typing of orbital lymphomas
Table 9
Comparative analysis of studies based on the no. of patients and the duration of period studied
Table 10
Comparative analysis of Age and sex distribution of orbital tumors
Table 11
Comparative analysis of clinical presentation
Table 12
Comparative analysis of percentage distribution of orbital tumors in various studies
Table 13
Percentage distribution of lacrimal gland tumors with epithelial and nonepithelial origin
Table 14
Comparative analysis of orbital lymphomas in various studies
Table 15
Reporting of pattern of Follicular lymphoma
| S. No. | Reporting of pattern | Proportion follicular |
| 1. | Follicular | >75% |
| 2. | Follicular and diffuse | 25-75% |
| 3. | Focally follicular | <25% |
| 4. | Diffuse | 0% |
Table 16
Comparative analysis of secondaries in various studies
Figure 1
Gross image of Dermoid cyst: Grey white cystic specimen measuring 1.5 x1 cm. Cut surface shows hair structures
Figure 2
H&E 10X Dermoid cyst lined by stratified squamous epithelium and subepiithelium shows dermal appendages
Figure 3
Embryonal Rhabdomyosarcoma: 15 year old patient presented with right eye proptosis. CT scan image showing soft tissue mass in the superomedial orbital space
Figure 4
H&E 10X Embryonal RMS: composed of primitive mesenchymal cells, small, polyhedral, oval and spindle cells with lightly amphophilic cytoplasm and cells with more cytoplasmic eosinophilia and elongated, “tadpole,” strap,” or “spider” cells and myxoid appearance of stroma
Figure 8
H&E 10X Pleomorphic adenoma with epithelial component showing tubules and sheets and mesenchymal component showing chondromyxoid material
Figure 9
Gross image of Adenoid Cystic Carcinoma: lacrimal gland mass measuring 2x1 cm. Cut surface showing grey white areas.
Figure 10
H&E 10X Adenoid cystic carcinoma showing cribriform pattern with small hyperchromatic cells
Discussion
Most common pediatric tumors are Dermoid cysts, Capillary hemangiomas and RMS.8, 9 Most common adult tumors are Lymphoid tumors, Cavernous hemangiomas and Meningiomas.5, 6 Most lymphomas are low-grade B-cell lymphoma, with extranodal marginal zone lymphoma (ENMZL) as the most common type.12
In the present study out of 54 cases, benign tumors (70.3%) were found to be common than malignant tumors (29.6%). In Tanushree et al 201513 out of 48 patients, benign tumors accounted for 90% and malignant 10% of the cases. In Radha et al 200514 out of 24 patients studied 70.8% accounted for benign tumors and 29.2% malignant tumors. Thus correlating with Tanushree et al, Radha et al and Jasna et al. But in Boriana et al 200715 malignant tumors were found to more common.
Figure 17
H&E 40X of Sinonasal Adenocarcinoma showing glandular pattern lined by neoplastic tumor epithelial cells
Figure 18
Gross image of Orbital extension of Conjunctival Squamous Cell Carcinoma: Irregular mass measuring 2x2 cm. Cut surface shows grey yellow to grey black areas
Figure 19
H&E 40 X Conjunctival Squamous Cell Carcinoma: slands and nests of polygonal cell with abundant cytoplasm and pleomorphic nucleus
Among the benign tumors, dermoid cyst was found to be most common(33.3%). This correlated with Tanushree et al.13 Other studies show varied percentages. 88% of the dermoid cysts were seen in 1st and 2nd decade. Dermoid cyst is the most common orbital cystic lesion in children. It accounts for over 40% of all orbital lesions of childhood and for 89% of all orbital cystic lesions of childhood that come to the biopsy or surgical removal.16
In the present study, maximum number of patients were in 1st, 2nd and 5th decades. A total of 24 (44.4%) orbital tumors were seen in 1st and 2nd decades. Of these, 21 cases (87.5%) were benign and 3 cases (12.5%) were malignant. Thus benign tumors were the majority in the first and second decades. Of the benign tumors, dermoid cysts predominated. In the present study, among the malignant tumors in childhood age group, 2 cases of embryonal rhabdomyosarcoma were diagnosed based on the morphology and 1 case of secondary with direct extension from ocular retinoblastoma. Of the 2 cases of RMS, 1 case was seen in 13 year old male patient and other case was seen in 15 year old male child. Both cases presented with proptosis.
In Jasna et al 200417 and Saha somnath et al 20021 also, there were 2 cases of rhabdomyosarcoma. In Saha somnath et al 20021 pediatric tumors were rare (22.6%). Most of the orbital tumors of childhood are distinct from the tumors that occur in adults. The most common orbital malignancy in childhood is Rhabdomyosarcoma.18 However, the majority of pediatric orbital tumors are benign and usually include developmental cysts, capillary hemangioma and hamartoma.19
Rhabdomyosarcoma is malignant soft tissue sarcoma that recapitulates the phenotypic and biological features of skeletal muscle.20 RMS is the most common soft tissue sarcoma in children.21, 22 About 42% of patients with orbital rhabdomyosarcoma are aged 5–9 years; they present with proptosis or dysconjugate gaze.23 Embryonal rhabdomyosarcomas constitute the most common subtype of rhabdomyosarcoma of the orbit by far. A special subtype of embryonal rhabdomyosarcoma is botryoid rhabdomyosarcoma (involving the conjunctiva).24 Overall 5-year survival rates have improved to more than 80% with the combined use of surgery, radiation therapy, and chemotherapy in patients with localized orbital disease.23, 24, 25
In this study, lacrimal gland lesions accounted for 12 cases (22.2%). Out of 12 cases, 3 cases were lacrimal ductal cyst, 4 cases pleomorphic adenoma, 3 cases adenoid cystic carcinoma and 2 cases non hodgkins lymphoma. In Tanushree et al13 of 5 cases,4 cases were pleomorphic adenoma and 1 case of adenoid cystic carcinoma. In Radha et al14 out of 2 cases, 1 case of pleomorphic adenoma and 1 case of adenoid cystic carcinoma. In Jasna et al 2004 out of 25 cases, 2 cases were pleomorphic adenoma. Thus all were of epithelial origin in Tanushree et al, Radha et al and Jasna et al. Lacrimal gland lesions represent 5–25% of orbital tumors, and the proportion in the literature that are epithelial in origin, range from 23% to 70% of biopsied cases.26, 27, 28, 29
In the present study, among the lacrimal gland tumors, benign tumors were 44.4% and malignant 55.5%. Thus malignant tumors were slightly common than benign tumors. The age group ranged from 28 to 62 years. Thus in Radha et al14 among the lacrimal gland tumors 50% benign and 50% were malignant.us the present study shows similar observation as seen in Radha et al study. In Tanushree et al 13mong the lacrimal gland tumors, 80% were benign and 20% were malignant. Thus, benign tumors were in much greater number in Tanushree et al. In Jasna et al, only benign tumors were seen.
Shields et al 17 in 2004 concluded that approximately 55% are benign and 45% are malignant. In Perez et al,30 out of 18 cases, 66.7% were Adenoid cystic carcinoma, 27.8% were pleomorphic adenoma and 5.5% were carcinoma ex pleomorphic adenoma. This indicates a different distribution of benign and malignant epithelial lesions with a higher rate of malignancy.
In the present study, Pleomorphic adenoma was found to be most common benign epithelial tumor. Similar observation was found in Tanushree et al,13 Radha et al,14 Jasna et al.18 Although pleomorphic adenomas are histologically benign, incomplete excision will lead to recurrences and even malignant transformation. Hence, when suspected, lateral orbitotomy is mandatory and entire tumor must be excised enbloc.31
In the present study,out of 9 cases of lacrimal gland tumors, there were 3 cases of adenoid cystic carcinoma. It was found to be most common malignant epithelial tumor. In Radha et al.14 Whereas in Tanushree et al,13 mucoepidermoid was found to be common. In Jasna et al,18 there were no malignant cases.
In the present study, all the three cases of adenoid cystic carcinoma were seen in 3rd decade (21-30). Thus it is seen in young adults.Whereas in Radha et al14 it was seen in older age group (6th decade). Lacrimal gland ACC generally affects young to middle aged patients (range 6.5–79 years).3
The outcome for patients with ACC in the lacrimal gland is reportedly poorer than that with ACC in the salivary gland.32 Thorough histologic examination of ACC in order to detect any solid or dedifferentiated component and evaluation of the margins as well as perineural invasion are important. Major cause of death is intracranial spread hastened by perineural invasion. Treatment is exenteration and post- operative radiotherapy.14
In the present study, out of 9 cases of lacrimal gland tumors, 2 cases (22%) were non epithelial. Of the non epithelial tumors, all were non hodgkins lymphomas. After running a panel of markers, all were confirmed as Diffuse Large Bcell Lymphoma. Thus DLBCL was found to be most common type of lymphoma among lacrimal gland tumors. In Sjo LD, et al33 out of 15 primary lacrimal sac lymphomas, five cases (33%) were diffuse large B cell lymphomas.
The Ocular Adnexal Lymphoma (OAL) represents malignant lymphoid neoplasms, which can develop as primary or secondary tumor manifestations. Lymphoma localized in the ocular region (eyelid, conjunctiva, lacrimal drainage system, orbit, and intraocular) is one of the most common orbital malignancies.34, 17 78% of lymphomas involving the ocular adnexa are primary, whereas 22% are secondary.12 OAL is primarily a disease of older adults (peak age 65 years) with a slight female preponderance.33 The deep orbital tissue is considered as true extranodal/nonfunctional mucosa-associated tissue (ENMZL) whereas the lacrimal gland, the conjunctiva, and the lacrimal sac are considered as functional mucosa-associated tissues.35 Mucosa associated lymphoid tissue lymphoma (MALT) is therefore not synonymous with ENMZL and is characterized by mucosal location and lymphoepithelial lesions. Lymphoma arising in the lacrimal sac was surprisingly predominantly DLBCL.33
FL are BCL-2 and CD10 positive in 85% of cases: BCL-2 is quite specific versus germinal centers. CD10 is quite specific versus other small B lymphomas. They also stain positive for BCL-6 and show expansion of follicular dendritic cell networks staining positive for CD21, CD23, and CD35. They are graded as low and high grade.
LOW GRADE -0 to 15 centroblasts per high power field.
HIGH GRADE –more than 15 centroblasts per high power field.36
In the present study, there were 6 cases (11%) of secondaries. Of these, 5 cases were of direct extension and 1 case of metastatic deposit. Of the 5 cases of direct extension, there was 1 case each of sinonasal adenocarcinoma extending from paranasal sinus, 1 case of squamous cell carcinoma extending from conjunctiva, 1 case of retinoblastoma extending from eye and 2 cases of choroidal malignant melanoma. Metastatic deposit was from breast carcinoma.
In the present study, out of 54 cases, one case of solitary fibrous tumor is seen on histopathology. IHC revealed CD 34 positivity. Hemangiopericytomas and Solitary fibrous tumors are uncommon neoplasms found in orbit. Local recurrences of SFT are possible and usually follow an incomplete initial excision.37 In Furusato et al 2010,36 Forty-one fibroblastic orbital tumors, originally diagnosed as hemangiopericytomas (n = 16), fibrous histiocytomas (n = 9), mixed tumors (hemangiopericytomas/fibrous histiocytoma) (n = 14), and giant cell angiofibromas of orbit (n = 2) between 1970 and 2009, were retrieved, the Ophthalmic Registry, at the Armed Forces Institute of Pathology. Slides and clinical records were reviewed, analyzed, and compared. IHC was performed for CD34, CD99, Bcl-2, Ki-67, and p53 and all cases were reclassified as solitary fibrous tumor (41/41).
In Furusato et al 2010,36 overlapping features with soft tissue giant cell fibroblastoma were observed. IHC revealed positivity for CD34 in all cases (100%), p53 in 85%, CD99 in 67.5%, and Bcl-2 in 47.5%. Although Ki-67 labeling was seen in all cases, it ranged from less than 1% in 54.3% of cases to 5% to 10% in 20% of cases.
In the present study, 4 cases(7.4%) of Meningioma are seen and 2 cases(3.2%) of Schwannomas (confirmed on IHC–S100 positive). All the patients presented with axial proptosis and other findings such as diminution of vision, defective pupillary reaction and optic atrophy. Of these, 1 case was seen in 1st decade and 4th decade each and 2 cases seen in 5th decade. All the cases presented as intraconal mass. Of these, 3 cases diagnosed as Meningothelial Meningioma, WHO grade 1 and 1 case as Angiomatous Meningioma WHO grade 1. In Tanushree et al 2015,13 there were 3 cases (6%) of meningioma and 2 cases (4%) of schwannoma. All the patients had axial proptosis and other findings such as diminution of vision, defective pupillary reaction and optic atrophy. Thus correlating with Tanushree et al study. In Jasna et al 2004,18 there were 4 cases(16%) of meningioma. In Saha Somnath et al 2002,1 there was 1 case (3%) of schwannoma.
Meningiomas can arise from the optic nerve or extend into the orbit from adjacent structures.38 The age at presentation of patients with optic nerve meningiomas is typically younger than for intracranial meningiomas.39 A number of meningioma subtypes have been proposed through the years, and the current (2016) World Health Organization (WHO) classification includes 15 named entities.40
Intraorbital meningiomas were most frequently of the meningothelial or transitional subtypes and were WHO grade 1. Significant changes that affect tumor grade are further classified (1) meningiomas showing central nervous system invasion as grade II rather than grade III (2) meningiomas with 4 or more mitotic figures per 10 high-power fields (HPFs) as grade II (3) Clear Cell and Chordoid Meningiomas as grade II (4) Papillary and Rhabdoid Meningiomas as grade III, and (5) tumors with 20 or more mitotic figures per 10 HPFs as grade III.41
In Deepali Jain et al 2010,42 a total of 51 intraorbital meningiomas were reviewed. Meningothelial type was most common (25 of 51 tumors; 49%). Most (47 of 51; 92%) of the tumors were WHO grade I. They concluded that Intraorbital meningiomas were most frequently of the meningothelial or transitional subtypes and were WHO grade I.
Schwannomas are benign peripheral nerve sheath tumors derived from Schwann cells. Nuclear atypia with hyperchromatic pleomorphic nuclei can be observed in Ancient Schwannoma.43 Mitotic figures with counts of 6 mitoses per 10 HPF can be observed. True malignant change of Schwannoma is very rare.
Article DOI
