Correspondence Can J Ophthalmol 2013;48:e151–e154 0008-4182/13/$-see front matter & 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2013.07.008
15. Lacey J, Ramakrishna N, Hamer A, et al. Grain fungi. In: Arora DK, Mukerji KG, Marth EH, eds. Handbook of Applied Mycology. Volume 3: Foods and Feeds. New York: Marcel Dekker, 1991:121-78.
Pigmented conjunctival growing lesion in a teenager: nevus or melanoma? Conjunctival melanoma (CM) is a rare tumour (0.06–0.74 case/million1,2), with a 10-year melanoma-related mortality rate around 30%.1,3 It arises from epithelial melanocytes and may develop from primary acquired melanosis, pre-existing nevus, or de novo in white adults. The spectrum of these tumours differs in the pediatric age group, which are predominantly benign nevi rarely evolving into melanoma.4 We present a case of a teenager with a growing pigmented conjunctival lesion, with pathologic characteristics of malignancy. A 15-year-old male presented with a conjunctival lesion since childhood that showed growth during the previous year (Fig. 1A–C). Ocular examination revealed an 11 9mm temporal pigmented mass, adjacent to the limbus. Excisional biopsy was proposed, but parents rejected that option. Two months later, the mass showed nodular growth in addition to basal growth (Fig. 1D). Wide microsurgical excisional biopsy with 3-mm free margins was performed, working with the “no-touch” technique. Microscopic examination showed a nodular lesion composed of a proliferation of confluent atypical epithelioid cells nests with nuclear pleomorphism involving fullthickness conjunctival epithelium with ulceration (Fig. 2A, 2B). It also extended into the underlying stroma, with lack
of maturation, focal dense lymphocytic infiltrate, and epithelial inclusion cysts. Surgical margins were free. Immunohistochemically, the tumour cells stained for melanocytic markers HMB-45 (Fig. 2C), S100, and Melan A. The Ki-67 growth fraction ranged from 10% to 25% (Fig. 2D). This marker has an accepted role in distinguishing benign from malignant lesions. According to Jakobiec et al.,5 melanomas display more than 10% nuclear positivity among all cells counted, whereas current nevi display approximately 1%. First diagnosis was juvenile conjunctival nevus (JCN) with atypical cells versus CM. Based on the development of ulceration, HMB-45 positivity, and the high proliferation index, the lesion as described represents a malignant transformation of a conjunctival nevus. The term melanoma in situ is not used anymore. Oncologic examination was performed obtaining negative results for regional lymph nodes and systemic extension by CT body scan including neck, chest, and abdomen examination. Ten months after biopsy, no signs of recurrence or systemic extension were found. CM is rare in children. In Triay et al.’s1 series of CM (170 cases), all patients were older than 35 years at the diagnosis time, except 2 of them, aged 20 and 22 years. In Shields and Shields’4 review (1643 cases), no patients with CM were younger than 20 years. Taban and Traboulsi,6
Fig. 1 — A, Pigmented temporal flat conjunctival lesion 7 years before examination. B, Two years later, lesion increased slightly in size and pigmentation. C, Conjunctival pigmented and elevated mass, reaching the limbus, with marked vascularization at first ocular examination. D, Two months later, it presented evident growth with conjunctival ulceration.
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Correspondence
Fig. 2 — A, Light microscopy shows a proliferation involving full thickness of conjunctival epithelium by nests of cells containing melanin with surface layers ulceration and intraepithelial cysts (hematoxylin and eosin staining, original magnification 2). B, Nests of atypical epithelioid cells with nuclear pleomorphism (hematoxylin and eosin staining, original magnification 40). C, Positivity for HMB-45 (original magnification 40). D, Growth fraction between 10% and 25% in Ki-67 proliferative marker (original magnification 40).
in a review of CM in children younger than 15 years (from 1965 to 2006), found only 8 published patients with clinical details (8–14 years old). Three of them arose from pre-existing nevus, as the present case, and 2 cases showed metastasis in the follow-up. In our experience, reviewing more than 300 conjunctival tumours, 149 (48%) were melanocytic and 129 (87%) were benign; we found only 8 CM, with the youngest patient being 38 years old.3 Nevus is the most common conjunctival tumour in children. Over time it can change in size and pigmentation, and show cysts, with less than 1% risk for transformation into malignant melanoma, which usually occurs during the adult years.3,4 Nevertheless, histologic pattern in a growing conjunctival nevus in children and adolescents can be difficult to differentiate from melanoma. Growing conjunctival nevi can display extensive junctional activity, nuclear pleomorphism, and lack of maturation in the subepithelial component, which are worrisome characteristics for melanoma in adults. Thiagalingam et al.7 identified a subcategory of childhood nevi displaying a confluent growth pattern and lack of maturation with no ulceration and rare mitotic activity that was defined as JCN, but HMB-45 and a higher Ki-67 proliferation index may indicate melanoma. The present case shows characteristics more consistent with CM than with JCN, such as ulceration, mitotic activity, and HMB-45 positivity. The differential diagnosis between them may present a diagnostic dilemma.
In conclusion, CM is a highly malignant tumour that is rare in children. Nonetheless, it should be considered, to achieve early and accurate diagnosis. Excisional biopsy with security margins is recommended in any growing suspicious nevus to prevent local recurrence and systemic dissemination. Anna Burgués-Ceballos, Maria Antonia Saornil, Ciro García-Alvarez, Elena García Lagarto Hospital Clı´nico Universitario de Valladolid, Valladolid, Spain. Correspondence to: Anna Burgue´s-Ceballos, MD: [email protected]
REFERENCES 1. Triay E, Bergman L, Nilsson B, All-Ericsson C, Seregard S. Time trends in the incidence of conjunctival melanoma in Sweden. Br J Ophthalmol. 2009;93:1524-8. 2. Yu GP, Hu DN, McCormick S, Finger PT. Conjunctival melanoma: is it increasing in the United States? Am J Ophthalmol. 2003;135:800-6. 3. Saornil MA, Becerra E, Mendez MC, Blanco G. Conjunctival tumors. Arch Soc Esp Oftalmol. 2009;84:7-22. 4. Shields CL, Shields JA. Conjunctival tumors in children. Curr Opin Ophthalmol. 2007;18:351-60. 5. Jakobiec FA, Colby K, Bajart AM, Saragas SJ, Moulin A. Immunohistochemical studies of atypical conjunctival melanocytic nevi. Arch Ophthalmol. 2009;127:970-80. 6. Taban M, Traboulsi EI. Malignant melanoma of the conjunctiva in children: a review of the international literature 1965-2006. J Pediatr Ophthalmol Strabismus. 2007;44:277-82.
CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013
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Correspondence 7. Thiagalingam S, Johnson MM, Colby KA, Zembowicz A. Juvenile conjunctival nevus. Clinicopathologic analysis of 33 cases. Am J Surg Pathol. 2008;32:399-406.
Can J Ophthalmol 2013;48:e154–e156 0008-4182/13/$-see front matter & 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2013.08.010
Orbital signet-ring cell lymphoma of diffuse, large, B-cell type
preseptal plane to the mid-orbit nasally and into the extraocular muscle cone. Anteriorly the mass extended up to the bridge of the nose; the bony orbit showed no change, and there was no involvement of the nose or sinuses (Fig. 1B, 1C). Microscopic examination of the incision biopsy from the orbital mass showed a diffusely infiltrating cellular tumour composed of large, noncohesive cells in a sclerotic stroma with foci of necrosis. Many of the tumour cells had large, round, cytoplasmic vacuoles and eccentrically placed atypical nuclei (Fig. 2A). Immunostaining was positive for leukocyte common antigen (Fig. 2B) and CD20 (Fig. 2C) in all tumour cells. Fifty-three percent of the cells were immunoreactive for Bcl-6. A positive reaction was seen for lambda light-chain restriction. Ki-67 activity was 70% to 80% (Fig. 2D). The tumour cells were negative for CD5, CD10, CD23, HMB45, pancytokeratin, S100, epithelial membrane antigen, smooth muscle actin, cytokeratin 7, and cytokeratin 20. They were also negative on periodic acid–Schiff (PAS) and Alcian blue staining. Systemic examination and bone marrow examination were normal. Our patient was thus categorized as Ann Arbor stage I and American Joint Committee on Cancer stage T3N0M0. He was started on a CHOP regimen composed of cyclophosphamide, hydroxydaunorubicin, Oncovin (Vincristine), and prednisolone. In addition, external beam radiotherapy (EBRT) of 4000 cGy was also given. A marked reduction in size of the tumour was seen after the first cycle, and a CT scan at the end of third cycle did not show any residual tumour. Ocular adnexal lymphomas are rare, accounting for only 1% to 2% of all lymphomas.2 Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma that commonly presents with systemic involvement.3 Most ocular adnexal lymphomas are low-grade extranodal marginal zone lymphomas of B-cell type. Morphologic variants of DLBCL include centroblastic, immunoblastic, T-cell/histiocyte-rich and anaplastic subtypes.4 SRCL, most commonly described as a variant of follicular lymphoma, has been rarely described in DLBCL.5 To date, only about 50 cases of SRCL have been described in the literature.6 Most commonly affecting the lymph nodes, SRCLs have been described to involve the skin, stomach, thyroid,1 small bowel, and bone marrow.7–12 Orbital SRCL is rare, with only 1 such case described previously in the literature.13 Our case represents the second reported case of orbital SRCL. Based on the morphologic and immunohistochemical features, SRCLs are classified into 3 subtypes: clear vacuole type, Russell
Signet-ring cell lymphoma (SRCL) is a rare morphologic variant of non-Hodgkin lymphoma with a “signet-ring cell” appearance. It has been described in both B-cell and T-cell lymphomas.1 We report an orbital SRCL of diffuse large B-cell type in a 60-year-old male, which, to the best of our knowledge, is only the second case to be described in the literature. A 60-year-old male presented to our clinic with complaints of painless, gradually progressive protrusion of his left eye for 18 months. External examination of the left eye showed a firm swelling superomedial and inferomedial to the globe associated with lid swelling (Fig. 1A). The distinct masses were nodular, and the posterior extent could not be ascertained. Orbital rims were intact and the overlying skin was normal. The masses were not freely mobile. Anterior segment evaluation, visual acuity, and fundus examination were normal. Computed tomography showed a well-defined hypodense to isodense, lobulated soft tissue lesion on the left side extending from the
Fig. 1 — External examination of the left eye showing a firm to hard swelling, superomedial and inferomedial to the globe associated with lid swelling (A). CT shows a well-defined hypodense to isodense, lobulated soft tissue lesion on the left side extending from the preseptal plane to the mid-orbit medially and into the extraocular muscle cone within the orbit (B, C).
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CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013
15. Lacey J, Ramakrishna N, Hamer A, et al. Grain fungi. In: Arora DK, Mukerji KG, Marth EH, eds. Handbook of Applied Mycology. Volume 3: Foods and Feeds. New York: Marcel Dekker, 1991:121-78.
Pigmented conjunctival growing lesion in a teenager: nevus or melanoma? Conjunctival melanoma (CM) is a rare tumour (0.06–0.74 case/million1,2), with a 10-year melanoma-related mortality rate around 30%.1,3 It arises from epithelial melanocytes and may develop from primary acquired melanosis, pre-existing nevus, or de novo in white adults. The spectrum of these tumours differs in the pediatric age group, which are predominantly benign nevi rarely evolving into melanoma.4 We present a case of a teenager with a growing pigmented conjunctival lesion, with pathologic characteristics of malignancy. A 15-year-old male presented with a conjunctival lesion since childhood that showed growth during the previous year (Fig. 1A–C). Ocular examination revealed an 11 9mm temporal pigmented mass, adjacent to the limbus. Excisional biopsy was proposed, but parents rejected that option. Two months later, the mass showed nodular growth in addition to basal growth (Fig. 1D). Wide microsurgical excisional biopsy with 3-mm free margins was performed, working with the “no-touch” technique. Microscopic examination showed a nodular lesion composed of a proliferation of confluent atypical epithelioid cells nests with nuclear pleomorphism involving fullthickness conjunctival epithelium with ulceration (Fig. 2A, 2B). It also extended into the underlying stroma, with lack
of maturation, focal dense lymphocytic infiltrate, and epithelial inclusion cysts. Surgical margins were free. Immunohistochemically, the tumour cells stained for melanocytic markers HMB-45 (Fig. 2C), S100, and Melan A. The Ki-67 growth fraction ranged from 10% to 25% (Fig. 2D). This marker has an accepted role in distinguishing benign from malignant lesions. According to Jakobiec et al.,5 melanomas display more than 10% nuclear positivity among all cells counted, whereas current nevi display approximately 1%. First diagnosis was juvenile conjunctival nevus (JCN) with atypical cells versus CM. Based on the development of ulceration, HMB-45 positivity, and the high proliferation index, the lesion as described represents a malignant transformation of a conjunctival nevus. The term melanoma in situ is not used anymore. Oncologic examination was performed obtaining negative results for regional lymph nodes and systemic extension by CT body scan including neck, chest, and abdomen examination. Ten months after biopsy, no signs of recurrence or systemic extension were found. CM is rare in children. In Triay et al.’s1 series of CM (170 cases), all patients were older than 35 years at the diagnosis time, except 2 of them, aged 20 and 22 years. In Shields and Shields’4 review (1643 cases), no patients with CM were younger than 20 years. Taban and Traboulsi,6
Fig. 1 — A, Pigmented temporal flat conjunctival lesion 7 years before examination. B, Two years later, lesion increased slightly in size and pigmentation. C, Conjunctival pigmented and elevated mass, reaching the limbus, with marked vascularization at first ocular examination. D, Two months later, it presented evident growth with conjunctival ulceration.
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CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013
Correspondence
Fig. 2 — A, Light microscopy shows a proliferation involving full thickness of conjunctival epithelium by nests of cells containing melanin with surface layers ulceration and intraepithelial cysts (hematoxylin and eosin staining, original magnification 2). B, Nests of atypical epithelioid cells with nuclear pleomorphism (hematoxylin and eosin staining, original magnification 40). C, Positivity for HMB-45 (original magnification 40). D, Growth fraction between 10% and 25% in Ki-67 proliferative marker (original magnification 40).
in a review of CM in children younger than 15 years (from 1965 to 2006), found only 8 published patients with clinical details (8–14 years old). Three of them arose from pre-existing nevus, as the present case, and 2 cases showed metastasis in the follow-up. In our experience, reviewing more than 300 conjunctival tumours, 149 (48%) were melanocytic and 129 (87%) were benign; we found only 8 CM, with the youngest patient being 38 years old.3 Nevus is the most common conjunctival tumour in children. Over time it can change in size and pigmentation, and show cysts, with less than 1% risk for transformation into malignant melanoma, which usually occurs during the adult years.3,4 Nevertheless, histologic pattern in a growing conjunctival nevus in children and adolescents can be difficult to differentiate from melanoma. Growing conjunctival nevi can display extensive junctional activity, nuclear pleomorphism, and lack of maturation in the subepithelial component, which are worrisome characteristics for melanoma in adults. Thiagalingam et al.7 identified a subcategory of childhood nevi displaying a confluent growth pattern and lack of maturation with no ulceration and rare mitotic activity that was defined as JCN, but HMB-45 and a higher Ki-67 proliferation index may indicate melanoma. The present case shows characteristics more consistent with CM than with JCN, such as ulceration, mitotic activity, and HMB-45 positivity. The differential diagnosis between them may present a diagnostic dilemma.
In conclusion, CM is a highly malignant tumour that is rare in children. Nonetheless, it should be considered, to achieve early and accurate diagnosis. Excisional biopsy with security margins is recommended in any growing suspicious nevus to prevent local recurrence and systemic dissemination. Anna Burgués-Ceballos, Maria Antonia Saornil, Ciro García-Alvarez, Elena García Lagarto Hospital Clı´nico Universitario de Valladolid, Valladolid, Spain. Correspondence to: Anna Burgue´s-Ceballos, MD: [email protected]
REFERENCES 1. Triay E, Bergman L, Nilsson B, All-Ericsson C, Seregard S. Time trends in the incidence of conjunctival melanoma in Sweden. Br J Ophthalmol. 2009;93:1524-8. 2. Yu GP, Hu DN, McCormick S, Finger PT. Conjunctival melanoma: is it increasing in the United States? Am J Ophthalmol. 2003;135:800-6. 3. Saornil MA, Becerra E, Mendez MC, Blanco G. Conjunctival tumors. Arch Soc Esp Oftalmol. 2009;84:7-22. 4. Shields CL, Shields JA. Conjunctival tumors in children. Curr Opin Ophthalmol. 2007;18:351-60. 5. Jakobiec FA, Colby K, Bajart AM, Saragas SJ, Moulin A. Immunohistochemical studies of atypical conjunctival melanocytic nevi. Arch Ophthalmol. 2009;127:970-80. 6. Taban M, Traboulsi EI. Malignant melanoma of the conjunctiva in children: a review of the international literature 1965-2006. J Pediatr Ophthalmol Strabismus. 2007;44:277-82.
CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013
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Correspondence 7. Thiagalingam S, Johnson MM, Colby KA, Zembowicz A. Juvenile conjunctival nevus. Clinicopathologic analysis of 33 cases. Am J Surg Pathol. 2008;32:399-406.
Can J Ophthalmol 2013;48:e154–e156 0008-4182/13/$-see front matter & 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2013.08.010
Orbital signet-ring cell lymphoma of diffuse, large, B-cell type
preseptal plane to the mid-orbit nasally and into the extraocular muscle cone. Anteriorly the mass extended up to the bridge of the nose; the bony orbit showed no change, and there was no involvement of the nose or sinuses (Fig. 1B, 1C). Microscopic examination of the incision biopsy from the orbital mass showed a diffusely infiltrating cellular tumour composed of large, noncohesive cells in a sclerotic stroma with foci of necrosis. Many of the tumour cells had large, round, cytoplasmic vacuoles and eccentrically placed atypical nuclei (Fig. 2A). Immunostaining was positive for leukocyte common antigen (Fig. 2B) and CD20 (Fig. 2C) in all tumour cells. Fifty-three percent of the cells were immunoreactive for Bcl-6. A positive reaction was seen for lambda light-chain restriction. Ki-67 activity was 70% to 80% (Fig. 2D). The tumour cells were negative for CD5, CD10, CD23, HMB45, pancytokeratin, S100, epithelial membrane antigen, smooth muscle actin, cytokeratin 7, and cytokeratin 20. They were also negative on periodic acid–Schiff (PAS) and Alcian blue staining. Systemic examination and bone marrow examination were normal. Our patient was thus categorized as Ann Arbor stage I and American Joint Committee on Cancer stage T3N0M0. He was started on a CHOP regimen composed of cyclophosphamide, hydroxydaunorubicin, Oncovin (Vincristine), and prednisolone. In addition, external beam radiotherapy (EBRT) of 4000 cGy was also given. A marked reduction in size of the tumour was seen after the first cycle, and a CT scan at the end of third cycle did not show any residual tumour. Ocular adnexal lymphomas are rare, accounting for only 1% to 2% of all lymphomas.2 Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma that commonly presents with systemic involvement.3 Most ocular adnexal lymphomas are low-grade extranodal marginal zone lymphomas of B-cell type. Morphologic variants of DLBCL include centroblastic, immunoblastic, T-cell/histiocyte-rich and anaplastic subtypes.4 SRCL, most commonly described as a variant of follicular lymphoma, has been rarely described in DLBCL.5 To date, only about 50 cases of SRCL have been described in the literature.6 Most commonly affecting the lymph nodes, SRCLs have been described to involve the skin, stomach, thyroid,1 small bowel, and bone marrow.7–12 Orbital SRCL is rare, with only 1 such case described previously in the literature.13 Our case represents the second reported case of orbital SRCL. Based on the morphologic and immunohistochemical features, SRCLs are classified into 3 subtypes: clear vacuole type, Russell
Signet-ring cell lymphoma (SRCL) is a rare morphologic variant of non-Hodgkin lymphoma with a “signet-ring cell” appearance. It has been described in both B-cell and T-cell lymphomas.1 We report an orbital SRCL of diffuse large B-cell type in a 60-year-old male, which, to the best of our knowledge, is only the second case to be described in the literature. A 60-year-old male presented to our clinic with complaints of painless, gradually progressive protrusion of his left eye for 18 months. External examination of the left eye showed a firm swelling superomedial and inferomedial to the globe associated with lid swelling (Fig. 1A). The distinct masses were nodular, and the posterior extent could not be ascertained. Orbital rims were intact and the overlying skin was normal. The masses were not freely mobile. Anterior segment evaluation, visual acuity, and fundus examination were normal. Computed tomography showed a well-defined hypodense to isodense, lobulated soft tissue lesion on the left side extending from the
Fig. 1 — External examination of the left eye showing a firm to hard swelling, superomedial and inferomedial to the globe associated with lid swelling (A). CT shows a well-defined hypodense to isodense, lobulated soft tissue lesion on the left side extending from the preseptal plane to the mid-orbit medially and into the extraocular muscle cone within the orbit (B, C).
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CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013
