PRIMARY MUCINOUS ADENOCARCINOMA OF THE EYELID Thomas M. Andrews, MD, Jack L. Gluckman, MD, and Mark A. Weiss, MD
Primary mucinous adenocarcinoma of the skin is a rare entity arising from eccrine sweat glands with a propensity for local recurrence and metastasis. This tumor has been widely reported in the ophthalmology literature, but not to our knowledge in the otolaryngology literature. A case of a 48-year-old man with a mucinous adenocarcinoma extensively involving the right eyelid and orbit necessitating craniofacial resection is presented together with a discussion of the pathology, clinical features, and management. 0 John Wiley & Sons, Inc. HEAD 81NECK 1992;14:303-307
Primary mucinous adenocarcinoma of the skin is a rare tumor that occurs most frequently in the head and This tumor arises from eccrine sweat glands with origin from the eyelid in approximately half of the cases.3 The natural history of the tumor includes a propensity for local recurrence after excision and occasional regional and distant metastases. This tumor has been widely reported in the ophthalmology literature, but to our knowledge, not in the otolaryngology literature. We therefore present a case report of a 48-year-old man with a primary mucinous adenocarcinoma of the
From the Departments of Otoiaryngoiogy and Maxiliofaciai Surgery (Drs. Andrews and Gluckman) and Pathology (Dr. Weiss), University of Cincinnati Medical Center, Cincinnati, Ohio. Address reprint requests to Dr. Gluckman at the Department of Otolaryngology and Maxillofacial Surgery, Mail Location 528, 231 Bethesda Avenue, Cincinnati, OH 45267-0528. Accepted for publication October 15, 1991 CCC 0148-6403/92/040303-05$04.00 0 1992 John Wiiey & Sons, Inc
Primary Mucinous Adenocarcinorna
right eyelid, with extensive involvement of the periorbita necessitating craniofacial resection for removal. Pertinent pathologic findings, clinical features, and management options are highlighted. CASE REPORT
A 50-year-old man was initially seen at the Department of Otolaryngology- Head and Neck Surgery at the University of Cincinnati with a 6-year history of gradually progressive rightsided periorbital swelling. Four years prior to his presentation, this had been diagnosed both clinically and histologically as a metastatic adenocarcinoma from an unknown primary after extensive evaluation failed t o reveal a primary source, and no other evidence of metastasis was demonstrated. At that time, the patient had undergone external-beam radiotherapy of 45 Gy to the periorbita as definitive treatment. This stabilized the process until several months prior to presentation, at which time the patient began experiencing increasing diplopia and periorbital swelling. On clinical evaluation, firm swelling of the superior and inferior eyelids with erythema was noted with diplopia on upward and medial gaze. Visual acuity was normal. Biopsy confirmed the presence of recurrent or persistent tumor. Computed tomographic (CT) scan demonstrated tumor involvement of the entire right globe and optic nerve, as well as the medial and inferior recti muscles (Figure 1).A metastatic workup was negative. It was selected to perform a craniofacial re-
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A
B FIGURE 1. (A, B) Axial and coronal CT images demonstrate an infiltrating right orbital mass involving the globe, extraocular muscles, and optic nerve.
FIGURE 2. (Left) Confluent nodular masses of carcinoma in retro-orbital soft tissue (hematoxylin & eosin, x40). (Right) Uniform population of cells having oval, frequently eccentric nuclei with vesicular chromatin and prominent nucleoli (hematoxylin & eosin, x250).
304
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section after preoperative balloon occlusion of the right internal carotid artery. Surgical ablation consisted of a frontal craniotomy, with exenteration of tumor from the cavernous sinus, right orbit, and ethmoid and sphenoid sinuses with complete en bloc removal of the agggressively invading tumor. The defect was reconstructed with a free rectus abdominus flap. The patient remains free of disease 2 years following resection. PATHOLOGY
Grossly, the deeply infiltrating tumor consisted of solid sheets and nodular masses extending into the orbicularis muscle, periorbital soft tissues, and optic nerve (Figure 2). The findings were compatible with those of primary mucinous adenocarcinoma with clusters of tumor cells with cytoplasmic mucin-containing vacuoles in pools of extracellular mucin. The neoplasm was composed of a uniform population of medium-sized cells with central or eccentric oval nuclei having finely granular to
vesicular chromatin and one or two prominent nucleoli. Tumor cells contained scanty eosinophilic and finely granular cytoplasm, with a few cells demonstrating increased cytoplasm with vacuoles. Scattered signet-ring cells were also present. The tumor was composed of single cells, loosely cohesive cords, or, more characteristically, clusters of cells (Figure 3). Immunohistologic studies demonstrated the neoplastic cells to be positive for cytokeratin (AEl/AE3) and focally positive for vimentin; cells did not mark for HMB-45, CLA, and S-100 protein. Cytoplasmic vacuoles stained for mucin (digested PAS, mucicarmine, and alcian blue at pH 2.5). Extracellular accumulations of mucins were focally present in the resection specimen (Figure 4). DISCUSSION
Primary mucinous adenocarcinoma of the skin is a rare malignant neoplasm first described by Lennox in 1952.l This lesion frequently arises in the
FIGURE 3. (Left) Neoplastic infiltrate of single cells in dermis of eyelid (hematoxylin & eosin, x125). (Right) Note signet-ring cells (arrows) with intracellular mucin vacuole displacing the nucleus (hematoxylin & eosin, X400).
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305
FIGURE 4. Focus of neoplastic cells floating in extracellular rnucin (M) (hematoxylin & eosin, ~250).
head and neck area, usually from the eyelids. It most commonly occurs in older men. No racial predilection has been found,. Wright and Font reported on 45 cases of mucinous adenocarcinoma, 78% of which occurred in the head and neck.' Forty-seven percent of these lesions involved the eyelid.'^^ Other sites of involvement include the scalp, as well the trunk and extremities.4 Clinical presentation usually consists of a painless red, pink, or bluish lesion in the form of a papule, cyst, or ulcer. The surface may be smooth or crusted. It may also present as a subcutaneous mass as in our case. It is usually slowgrowing and may be present for 1 t o 3 years or even as long as 20 years prior to clinical presentation. Locally, it gradually infiltrates into adjacent structures and has a propensity for local bony invasion. Aggressive lesions may occasionally lead to fatal result^.'^^ Regional metastasis is uncommon but has been reported in 5% to 15% of cases with distant metastasis reported in 2% to 7% of cases.''4
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Primary Mucinous Adenocarcinoma
Histologic examination of primary mucinous adenocarcinomas reveals uniform round or cuboidal cells with sialomucin-rich cytoplasmic vacuoles or extracellular mucin pools and positive histochemical staining for PAS, mucicarmine, and alcian blue (pH 2.5). However, mucinous adenocarcinomas of the breast, colon, ovary, rectus, and bronchus have similar histochemical reactions. Breast carcinoma is especially similar histologically. The key for the clinician is therefore to differentiate this lesion from metastatic adenocarcinoma. On light microscopy, metastatic lesions would be expected to show pleomorphism and moderately high mitotic activity. In addition, using electron microscopy, stem cell origin of primary sweat gland neoplasms can be determined and can be useful in differentiating these lesions from metastases.6 Nevertheless, it may occasionally be extremely difficult to differentiate these lesions histologically and, therefore, all patients should undergo a thorough search for a possible primary tumor site.
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July/August 1992
If no primary tumor is found, wide en bloc excision is the preferred treatment. Mohs’ surgery has been described for smaller lesion^.^ Localized recurrence after resection may occur in up to 37% of As regional metastases are rare, a therapeutic regional neck dissection is only indicated in the presence of palpable nodal spread, and prophylactic neck dissection is not indicated. Mucinous adenocarcinoma appears unresponsive to chemotherapy and radi~therapy.’~’ CONCLUSION
A case of a mucinous adenocarcinoma of the eyelid is presented with a view to increasing awareness of the entity for the practicing otolaryngologist. While well reported in the ophthalmology literature, the otolaryngology- head and neck literature appears devoid of any description of this condition.
Primary Mucinous Adenocarcinoma
REFERENCES
1. Lennox B, Pearse AGE, Richard HGH. Mucin-secreting tumors of the skin. J Path01 1952;64:865-880. 2. Wright JD, Font RL. Mucinous sweat gland adenocarcinoma of eyelid. Cancer 1979;441757- 1768. 3. Cohen KL, Peiffer RL, Lipper S. Mucinous sweat gland adenocarcinoma of the eyelid. A m J Ophthalmol 1981;92:183- 188. 4. Sanke RF. Primary mucinous adenocarcinoma of the eyelid. Ophthalmic Surg 1989;20:668-671. 5. Jakobiec FA, Austin P, Twamoto T, Trokel SL, Marquardt MD, Harrison W. Primary infiltrating signet ring carcinoma of the eyelids. Ophthalmology 1983;90:291-299. 6. Headington John T. Primary mucinous carcinoma of skin histochemistry and election. Cancer 1977;39:1055- 1063. 7. Weber PJ, Hevia 0, Gretzula JC, Rabinovitz HC. Primary mucinous carcinoma. J Dermatot Surg Oncol 1988;14: 170-172. 8. Yeung KY, Stinsm JC. Mucinous (adenocystic) carcinoma of sweat glands with widespread metastasis. Cancer 1977;39:2556-2562. 9. Santa-Cruz DJ, Meyers JH, Gnepp DR, Perez BM. Primary mucinous carcinoma of the skin. Br J Dermatol 1978;98:645-653.
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307
Primary mucinous adenocarcinoma of the skin is a rare entity arising from eccrine sweat glands with a propensity for local recurrence and metastasis. This tumor has been widely reported in the ophthalmology literature, but not to our knowledge in the otolaryngology literature. A case of a 48-year-old man with a mucinous adenocarcinoma extensively involving the right eyelid and orbit necessitating craniofacial resection is presented together with a discussion of the pathology, clinical features, and management. 0 John Wiley & Sons, Inc. HEAD 81NECK 1992;14:303-307
Primary mucinous adenocarcinoma of the skin is a rare tumor that occurs most frequently in the head and This tumor arises from eccrine sweat glands with origin from the eyelid in approximately half of the cases.3 The natural history of the tumor includes a propensity for local recurrence after excision and occasional regional and distant metastases. This tumor has been widely reported in the ophthalmology literature, but to our knowledge, not in the otolaryngology literature. We therefore present a case report of a 48-year-old man with a primary mucinous adenocarcinoma of the
From the Departments of Otoiaryngoiogy and Maxiliofaciai Surgery (Drs. Andrews and Gluckman) and Pathology (Dr. Weiss), University of Cincinnati Medical Center, Cincinnati, Ohio. Address reprint requests to Dr. Gluckman at the Department of Otolaryngology and Maxillofacial Surgery, Mail Location 528, 231 Bethesda Avenue, Cincinnati, OH 45267-0528. Accepted for publication October 15, 1991 CCC 0148-6403/92/040303-05$04.00 0 1992 John Wiiey & Sons, Inc
Primary Mucinous Adenocarcinorna
right eyelid, with extensive involvement of the periorbita necessitating craniofacial resection for removal. Pertinent pathologic findings, clinical features, and management options are highlighted. CASE REPORT
A 50-year-old man was initially seen at the Department of Otolaryngology- Head and Neck Surgery at the University of Cincinnati with a 6-year history of gradually progressive rightsided periorbital swelling. Four years prior to his presentation, this had been diagnosed both clinically and histologically as a metastatic adenocarcinoma from an unknown primary after extensive evaluation failed t o reveal a primary source, and no other evidence of metastasis was demonstrated. At that time, the patient had undergone external-beam radiotherapy of 45 Gy to the periorbita as definitive treatment. This stabilized the process until several months prior to presentation, at which time the patient began experiencing increasing diplopia and periorbital swelling. On clinical evaluation, firm swelling of the superior and inferior eyelids with erythema was noted with diplopia on upward and medial gaze. Visual acuity was normal. Biopsy confirmed the presence of recurrent or persistent tumor. Computed tomographic (CT) scan demonstrated tumor involvement of the entire right globe and optic nerve, as well as the medial and inferior recti muscles (Figure 1).A metastatic workup was negative. It was selected to perform a craniofacial re-
HEAD & NECK
July/August 1992
303
A
B FIGURE 1. (A, B) Axial and coronal CT images demonstrate an infiltrating right orbital mass involving the globe, extraocular muscles, and optic nerve.
FIGURE 2. (Left) Confluent nodular masses of carcinoma in retro-orbital soft tissue (hematoxylin & eosin, x40). (Right) Uniform population of cells having oval, frequently eccentric nuclei with vesicular chromatin and prominent nucleoli (hematoxylin & eosin, x250).
304
Primary Mucinous Adenocarcinorna
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section after preoperative balloon occlusion of the right internal carotid artery. Surgical ablation consisted of a frontal craniotomy, with exenteration of tumor from the cavernous sinus, right orbit, and ethmoid and sphenoid sinuses with complete en bloc removal of the agggressively invading tumor. The defect was reconstructed with a free rectus abdominus flap. The patient remains free of disease 2 years following resection. PATHOLOGY
Grossly, the deeply infiltrating tumor consisted of solid sheets and nodular masses extending into the orbicularis muscle, periorbital soft tissues, and optic nerve (Figure 2). The findings were compatible with those of primary mucinous adenocarcinoma with clusters of tumor cells with cytoplasmic mucin-containing vacuoles in pools of extracellular mucin. The neoplasm was composed of a uniform population of medium-sized cells with central or eccentric oval nuclei having finely granular to
vesicular chromatin and one or two prominent nucleoli. Tumor cells contained scanty eosinophilic and finely granular cytoplasm, with a few cells demonstrating increased cytoplasm with vacuoles. Scattered signet-ring cells were also present. The tumor was composed of single cells, loosely cohesive cords, or, more characteristically, clusters of cells (Figure 3). Immunohistologic studies demonstrated the neoplastic cells to be positive for cytokeratin (AEl/AE3) and focally positive for vimentin; cells did not mark for HMB-45, CLA, and S-100 protein. Cytoplasmic vacuoles stained for mucin (digested PAS, mucicarmine, and alcian blue at pH 2.5). Extracellular accumulations of mucins were focally present in the resection specimen (Figure 4). DISCUSSION
Primary mucinous adenocarcinoma of the skin is a rare malignant neoplasm first described by Lennox in 1952.l This lesion frequently arises in the
FIGURE 3. (Left) Neoplastic infiltrate of single cells in dermis of eyelid (hematoxylin & eosin, x125). (Right) Note signet-ring cells (arrows) with intracellular mucin vacuole displacing the nucleus (hematoxylin & eosin, X400).
Primary Mucinous Adenocarcinoma
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305
FIGURE 4. Focus of neoplastic cells floating in extracellular rnucin (M) (hematoxylin & eosin, ~250).
head and neck area, usually from the eyelids. It most commonly occurs in older men. No racial predilection has been found,. Wright and Font reported on 45 cases of mucinous adenocarcinoma, 78% of which occurred in the head and neck.' Forty-seven percent of these lesions involved the eyelid.'^^ Other sites of involvement include the scalp, as well the trunk and extremities.4 Clinical presentation usually consists of a painless red, pink, or bluish lesion in the form of a papule, cyst, or ulcer. The surface may be smooth or crusted. It may also present as a subcutaneous mass as in our case. It is usually slowgrowing and may be present for 1 t o 3 years or even as long as 20 years prior to clinical presentation. Locally, it gradually infiltrates into adjacent structures and has a propensity for local bony invasion. Aggressive lesions may occasionally lead to fatal result^.'^^ Regional metastasis is uncommon but has been reported in 5% to 15% of cases with distant metastasis reported in 2% to 7% of cases.''4
306
Primary Mucinous Adenocarcinoma
Histologic examination of primary mucinous adenocarcinomas reveals uniform round or cuboidal cells with sialomucin-rich cytoplasmic vacuoles or extracellular mucin pools and positive histochemical staining for PAS, mucicarmine, and alcian blue (pH 2.5). However, mucinous adenocarcinomas of the breast, colon, ovary, rectus, and bronchus have similar histochemical reactions. Breast carcinoma is especially similar histologically. The key for the clinician is therefore to differentiate this lesion from metastatic adenocarcinoma. On light microscopy, metastatic lesions would be expected to show pleomorphism and moderately high mitotic activity. In addition, using electron microscopy, stem cell origin of primary sweat gland neoplasms can be determined and can be useful in differentiating these lesions from metastases.6 Nevertheless, it may occasionally be extremely difficult to differentiate these lesions histologically and, therefore, all patients should undergo a thorough search for a possible primary tumor site.
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July/August 1992
If no primary tumor is found, wide en bloc excision is the preferred treatment. Mohs’ surgery has been described for smaller lesion^.^ Localized recurrence after resection may occur in up to 37% of As regional metastases are rare, a therapeutic regional neck dissection is only indicated in the presence of palpable nodal spread, and prophylactic neck dissection is not indicated. Mucinous adenocarcinoma appears unresponsive to chemotherapy and radi~therapy.’~’ CONCLUSION
A case of a mucinous adenocarcinoma of the eyelid is presented with a view to increasing awareness of the entity for the practicing otolaryngologist. While well reported in the ophthalmology literature, the otolaryngology- head and neck literature appears devoid of any description of this condition.
Primary Mucinous Adenocarcinoma
REFERENCES
1. Lennox B, Pearse AGE, Richard HGH. Mucin-secreting tumors of the skin. J Path01 1952;64:865-880. 2. Wright JD, Font RL. Mucinous sweat gland adenocarcinoma of eyelid. Cancer 1979;441757- 1768. 3. Cohen KL, Peiffer RL, Lipper S. Mucinous sweat gland adenocarcinoma of the eyelid. A m J Ophthalmol 1981;92:183- 188. 4. Sanke RF. Primary mucinous adenocarcinoma of the eyelid. Ophthalmic Surg 1989;20:668-671. 5. Jakobiec FA, Austin P, Twamoto T, Trokel SL, Marquardt MD, Harrison W. Primary infiltrating signet ring carcinoma of the eyelids. Ophthalmology 1983;90:291-299. 6. Headington John T. Primary mucinous carcinoma of skin histochemistry and election. Cancer 1977;39:1055- 1063. 7. Weber PJ, Hevia 0, Gretzula JC, Rabinovitz HC. Primary mucinous carcinoma. J Dermatot Surg Oncol 1988;14: 170-172. 8. Yeung KY, Stinsm JC. Mucinous (adenocystic) carcinoma of sweat glands with widespread metastasis. Cancer 1977;39:2556-2562. 9. Santa-Cruz DJ, Meyers JH, Gnepp DR, Perez BM. Primary mucinous carcinoma of the skin. Br J Dermatol 1978;98:645-653.
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