588932
research-article2015
IJSXXX10.1177/1066896915588932International Journal of Surgical PathologyLo et al
Case Report
Isolated Gallbladder Intramucosal Metastatic Melanoma With Features Mimicking Lymphoepithelial Carcinoma
International Journal of Surgical Pathology 2015, Vol. 23(5) 409–413 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896915588932 ijs.sagepub.com
Amy A. Lo, MD1, Joseph Peevey, MD1, Edward C. Lo, MD2, Joan Guitart, MD1, M. Sambasivia Rao, MD1, and Guang-Yu Yang, MD, PhD1 Abstract Malignant melanoma has a variety of morphologic patterns and can metastasize and mimic any type of neoplastic process creating significant diagnostic difficulty. When metastasis to the gastrointestinal system is identified, it is most commonly associated with widely metastatic disease. We report a rare case of isolated gallbladder intramucosal metastatic melanoma with features mimicking lymphoepithelial carcinoma in an adult patient who presented with cholecystitis. Additionally, we report the imaging and morphologic features and discuss the importance of these findings along with a clear clinical history and immunohistochemical profile to make a definitive diagnosis. Keywords gallbladder, metastatic melanoma, intramucosal metastasis
Introduction Malignant cutaneous melanoma is a very aggressive tumor that can metastasize to virtually any organ of the body and to bizarre sites years after diagnosis. The most common metastatic sites, apart from region lymph nodes, are the lungs, liver, brain, and colon.1 When gastrointestinal metastases occur, they carry a very poor prognosis and commonly involve multiple organs.2,3 However, isolated metastasis to the gallbladder is an extremely rare phenomenon. As reports of gallbladder metastasis are rare, autopsy studies provide most of the information regarding the disease process and demonstrate gallbladder involvement in 4% to 20% of cases with widely metastatic melanoma.4,5 We report an extremely rare case of isolated gallbladder intramucosal melanoma metastasis in an adult patient presenting with symptoms of cholecystitis. Histopathologically, the metastatic tumor showed features mimicking lymphoepithelial carcinoma, which was significantly distinct from the remote, primary cutaneous melanoma diagnosed 5 years earlier. We discuss the imaging findings, morphologic features, and the significance of morphology and immunohistochemistry as a practical approach for identifying intramucosal metastasis.
Computed tomography (CT) revealed a thickened gallbladder consistent with cholecystitis. Cholecystectomy was attempted, but terminated secondary to obscuring inflammation and a cholecystostomy tube was placed and the patient was started on a 10-day course of antibiotics. Five months later, the patient presented again with symptoms of cholecystitis and a laparoscopic cholecystectomy was successfully performed.
CT-Image Findings Grayscale oblique longitudinal sonographic image demonstrated gallbladder distention, dependent sludge, and gallbladder wall thickening (Figure 1A). This constellation of findings could represent cholecystitis. An additional focal mass-like thickening at the liver interface was seen and was nonspecific (Figure 1A). The tissue origin of this mass-like thickening could not be delineated sonographically. Coronal reformatted images from contrast-enhanced CT demonstrated a distended gallbladder with diffuse wall thickening (Figure 1B). The mass-like focus was less conspicuous but appeared to arise from the gallbladder wall, 1
Northwestern Memorial Hospital, Chicago, IL, USA University of Illinois at Chicago, IL, USA
2
Case Report Clinical Presentation A 59-year-old male presented with a 3-day history of episodic right upper quadrant pain accompanied by nausea.
Corresponding Author: Guang-Yu Yang, Department of Pathology, Northwestern University, Feinberg School of Medicine, 303 E Chicago Ave, Ward 4-176, Chicago, IL 60611, USA. Email: [email protected]
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
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International Journal of Surgical Pathology 23(5)
Figure 1. Sonographic and computed tomography imaging of the gallbladder.
Ultrasound of the gallbladder (longitudinal view) shows a distended gallbladder with abnormal wall thickening (yellow asterisks), some sludge (blue arrow) with no definitive gallstones, and a focal mass-like heterogeneous area (red arrowheads) inseparable from the gallbladder wall and adjacent liver (A). Coronal images from contrast-enhanced CT demonstrate a distended gallbladder with diffuse wall thickening (blue arrow) and a mass (red arrowheads) appearing to arise from the gallbladder wall, projecting intraluminally (B). Axial CT showed an enlarged lymph node (red arrow) abutting the gallbladder (blue arrow, C).
projecting intraluminally (Figure 1B). CT imaging convincingly separated this process from the adjacent liver. Axial CT image showed an enlarged lymph node abutting the gallbladder (Figure 1C). No other lesions or masses were identified.
Pathology and Immunohistochemistry Findings Laparoscopic cholecystectomy revealed an 8.6 × 3.8 × 3.5 cm gallbladder with roughened, hemorrhagic serosa and a thickened (1.5 cm) wall (Figure 2A). The gallbladder lumen contained friable pink-tan tissue, which was adherent to the mucosa of the neck, body, fundus, and cystic duct. Histologic sections revealed infiltration of the gallbladder mucosa by a poorly differentiated neoplasm (Figure 2B). The cells were large and epithelioid and exhibited marked pleomorphism with abundant eosinophilic cytoplasm, and vesicular nuclei harboring prominent centrally located nucleoli (Figure 2C). Numerous multinucleated cells, mitoses including atypical mitotic figures, were identified (Figure 2C). Areas with significant numbers of small lymphocytes and plasma cells were noted throughout the lesion mimicking features of lymphoepithelial carcinoma (Figure 2C). Despite extensive
histologic examination, no areas of invasion into the muscularis propria were identified and the lesion was located entirely within the mucosa (low-power view; Figure 2B). There was no lymphovascular invasion or pigment production and a regional lymph node was negative for metastasis. Immunostaining revealed tumor cells to be completely negative for cytokeratin AE1/AE3 (Clone AE 1/3, Dako, Carpinteria, CA; Figure 2D), but diffusely and strongly positive for S-100 protein (Ventana, prediluted, Tucson, AZ; Figure 2E) and Sox-10 (Biocare Medical, prediluted, Concord, CA; Figure 2F) with rare cells exhibiting positivity for Melan-A (Clone A103, pre-diluted, Dako, Carpinteria, CA; data not shown). All tumor cells were negative for EBER in situ hybridization (Dako). The overall immunoprofile was consistent with a diagnosis of intramucosal melanoma. Extensive review of the clinical history revealed a remote history of primary cutaneous desmoplastic melanoma of the right anterior neck that was excised 5 years prior. Histologic evaluation revealed the Breslow depth to be 3 mm and the Clark Level V, but ulceration could not be evaluated. Morphologically, there was a dermal proliferation of dendritic and highly atypical spindle-shaped
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
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Lo et al
Figure 2. Gross, microscopic, and immunohistochemical profile of gallbladder intramucosal metastatic melanoma.
The gallbladder lumen grossly contained friable pink-tan tissue, which was adherent to the mucosa of the neck, body, fundus, and cystic duct (A). Histologically, the poorly differentiated lesion was located entirely within the mucosa (B) with large, epithelioid, pleomorphic cells with prominent nucleoli (C). Immunohistochemically, the lesional cells were negative for cytokeratin AE1/AE3 (D), but positive for S100 (E) and Sox 10 (F).
melanocytes with pleomorphism and hyperchromasia (Figure 3A and B). These cells were imbedded in a sclerotic stroma with some myxoid features. No vascular invasion or satellitosis was identified and no lymph nodes were examined in association with this specimen. Lesional cells were negative for AE1/AE3 (Clone AE 1/3, Dako; data not shown), strongly positive for S100 (Ventana, prediluted; Figure 3C), focally positive for Melan-A (Clone A103, prediluted, Dako; data not shown), and strongly positive for Sox-10 (Biocare Medical, prediluted, Concord, CA; Figure 3D). Although the morphology of the primary cutaneous melanoma was drastically different than the gallbladder intramucosal melanoma, the immunostaining profile of both lesions was identical and intramucosal metastasis to the gallbladder was diagnosed.
Discussion Isolated metastasis of melanoma to the gallbladder or biliary tree is extremely rare with only 11 cases reported in the English literature.6 More commonly, metastasis to the gallbladder is one of a multitude of sites involved in widely metastatic disease. Five cases of isolated metastatic melanoma to the gallbladder were also reported in one study, but additional metastases were later identified in each case.6 An intramucosal isolated gallbladder metastasis has been reported in another case, but this patient later
developed widely metastatic disease.7 We report a case of isolated metastatic intramucosal melanoma to the gallbladder, which histopathologically demonstrated features mimicking lymphoepithelial carcinoma and was significantly distinct from the remote primary cutaneous melanoma. Per our clinical follow-up for 8 months after gallbladder resection, no addition metastases have been identified (data not shown). Patients with metastatic tumor in the gallbladder commonly present with cholecystitis and/or abdominal pain.8,9 In symptomatic patients, sonography is often the first utilized imaging modality because of the high accuracy in diagnosing cholelithiasis and high sensitivity for diagnosing cholecystitis.10 As seen in our case, the clinical and sonographic initial diagnosis was cholecystitis. The gross examination of the cholecystectomy specimen was correlated with the sonography and CT imaging findings and revealed a friable “mass-like” thickened mucosa involving the entire gallbladder including the gallbladder neck, body, fundus, and cystic duct. Histopathologically, an isolated gallbladder intramucosal poorly differentiated malignancy appeared as an incidental finding that was further confirmed as an extremely rare case of isolated gallbladder intramucosal metastasis of melanoma in a patient with a remote history of cutaneous melanoma. In our case, the intramucosal tumor histopathologically exhibited features mimicking lymphoepithelial carcinoma
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
412
International Journal of Surgical Pathology 23(5)
Figure 3. Histologic and immunohistochemical findings of the primary cutaneous melanoma of the anterior neck.
Low-power view shows a diffuse cell infiltrate deep to the epidermis (A) consisting of highly atypical spindle-shaped melanocytes in a background of desmoplasia (B). Immunostaining revealed lesional cells to be positive for S100 (C) and Sox-10 (D).
including pleomorphic, epitheloid neoplastic cells mixed with lymphoplasmacytic cells. Given this morphology, the main consideration in the differential diagnosis was poorly differentiated carcinoma, particularly EBERpositive lymphoepithelial carcinoma. However, negative staining for cytokeratin AE1/AE3 and EBER ruled out poorly differentiated carcinoma. Although the morphology was significantly distinct from the remote cutaneous desmoplastic melanoma with a predominantly spindle cell pattern, positive staining of S100 and SOX10 supported the diagnosis of isolated gallbladder intramucosal metastatic melanoma. It is well known that malignant melanoma has various morphologic patterns cytomorphologically and architecturally that can mimic any type of neoplastic process ranging from benign to malignant including but not limited to carcinoma, sarcoma, lymphoma, or even germ cell tumors.11 Distinct morphology of metastatic melanoma from its primary cutaneous source is also not an uncommon phenomenum.11 All of these pathologic variations cause tremendous diagnostic difficulty, particularly in cases of metastasis. Therefore, immunostaining is the most important ancillary approach to diagnose metastatic melanoma, especially in poorly differentiated tumors. Difficult
cases, like our case, which stain positively for S100 and Sox-10, solidify a diagnosis of melanoma. The diagnosis of metastatic melanoma in our case was further substantiated when we discovered the patient’s remote history of primary cutaneous melanoma excised 5 years previously. Although histologically both the primary melanoma and the intramucosal metastasis demonstrated drastically different morphology, both lacked pigment production and had identical immunohistochemical profiles, which favored a diagnosis of metastatic gallbladder intramucosal melanoma. In summary, we have documented a very rare case of isolated gallbladder intramucosal metastasis of melanoma in an adult patient with symptoms of cholecystitis and a remote history of primary cutaneous desmoplastic melanoma. Our case highlights the need for careful imaging analysis in patients with primary cutaneous melanoma, as even nonspecific changes identified may represent metastatic disease. Our case further demonstrates the importance of a broad differential diagnosis in evaluation of cases of poorly differentiated gallbladder tumors and emphasizes the importance of a clear clinical history and need for immunostaining to help deliver a definitive diagnosis.
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
413
Lo et al Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Vernadakis S, Rallis G, Danias N, et al. Metastatic melanoma of the gallbladder: an unusual clinical presentation of acute cholecystitis. World J Gastroenterol. 2009;15:3434-3436. 2. Velez AF, Penetrante RB, Spellman JE Jr, Orozco A, Karakousis CP. Malignant melanoma of the gallbladder: report of a case and review of the literature. Am Surg. 1995;61:1095-1098. 3. Crippa S, Bovo G, Romano F, Mussi C, Uggeri F. Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature. Melanoma Res. 2004;14:427-430. 4. Dasgupta TK, Brasfield RD. Metastatic melanoma of the gastrointestinal tract. Arch Surg. 1964;88:969-973.
5. Cellerino P, Corsi F, Morandi E, Foschi D, Trabucchi E. Metastatic melanoma of the gallbladder. Eur J Surg Oncol. 2000;26:815-816. 6. Katz RI, Cimino L, Vitkun SA. Preoperative medical consultations: impact on perioperative management and surgical outcome. Can J Anaesth. 2005;52:697-702. 7. Samplaski MK, Rosato EL, Witkiewicz AK, Mastrangelo MJ, Berger AC. Malignant melanoma of the gallbladder: a report of two cases and review of the literature. J Gastrointest Surg. 2008;12:1123-1126. 8. Langley RG, Bailey EM, Sober AJ. Acute cholecystitis from metastatic melanoma to the gall-bladder in a patient with a low-risk melanoma. Br J Dermatol. 1997;136: 279-282. 9. Dong XD, DeMatos P, Prieto VG, Seigler HF. Melanoma of the gallbladder: a review of cases seen at Duke University Medical Center. Cancer. 1999;85:32-39. 10. Anderson JC, Harned RK. Gray scale ultrasonography of the gallbladder: an evaluation of accuracy and report of additional ultrasound signs. AJR Am J Roentgenol. 1977;129:975-977. 11. Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma. Histopathology. 2000;36:387-402.
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
research-article2015
IJSXXX10.1177/1066896915588932International Journal of Surgical PathologyLo et al
Case Report
Isolated Gallbladder Intramucosal Metastatic Melanoma With Features Mimicking Lymphoepithelial Carcinoma
International Journal of Surgical Pathology 2015, Vol. 23(5) 409–413 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896915588932 ijs.sagepub.com
Amy A. Lo, MD1, Joseph Peevey, MD1, Edward C. Lo, MD2, Joan Guitart, MD1, M. Sambasivia Rao, MD1, and Guang-Yu Yang, MD, PhD1 Abstract Malignant melanoma has a variety of morphologic patterns and can metastasize and mimic any type of neoplastic process creating significant diagnostic difficulty. When metastasis to the gastrointestinal system is identified, it is most commonly associated with widely metastatic disease. We report a rare case of isolated gallbladder intramucosal metastatic melanoma with features mimicking lymphoepithelial carcinoma in an adult patient who presented with cholecystitis. Additionally, we report the imaging and morphologic features and discuss the importance of these findings along with a clear clinical history and immunohistochemical profile to make a definitive diagnosis. Keywords gallbladder, metastatic melanoma, intramucosal metastasis
Introduction Malignant cutaneous melanoma is a very aggressive tumor that can metastasize to virtually any organ of the body and to bizarre sites years after diagnosis. The most common metastatic sites, apart from region lymph nodes, are the lungs, liver, brain, and colon.1 When gastrointestinal metastases occur, they carry a very poor prognosis and commonly involve multiple organs.2,3 However, isolated metastasis to the gallbladder is an extremely rare phenomenon. As reports of gallbladder metastasis are rare, autopsy studies provide most of the information regarding the disease process and demonstrate gallbladder involvement in 4% to 20% of cases with widely metastatic melanoma.4,5 We report an extremely rare case of isolated gallbladder intramucosal melanoma metastasis in an adult patient presenting with symptoms of cholecystitis. Histopathologically, the metastatic tumor showed features mimicking lymphoepithelial carcinoma, which was significantly distinct from the remote, primary cutaneous melanoma diagnosed 5 years earlier. We discuss the imaging findings, morphologic features, and the significance of morphology and immunohistochemistry as a practical approach for identifying intramucosal metastasis.
Computed tomography (CT) revealed a thickened gallbladder consistent with cholecystitis. Cholecystectomy was attempted, but terminated secondary to obscuring inflammation and a cholecystostomy tube was placed and the patient was started on a 10-day course of antibiotics. Five months later, the patient presented again with symptoms of cholecystitis and a laparoscopic cholecystectomy was successfully performed.
CT-Image Findings Grayscale oblique longitudinal sonographic image demonstrated gallbladder distention, dependent sludge, and gallbladder wall thickening (Figure 1A). This constellation of findings could represent cholecystitis. An additional focal mass-like thickening at the liver interface was seen and was nonspecific (Figure 1A). The tissue origin of this mass-like thickening could not be delineated sonographically. Coronal reformatted images from contrast-enhanced CT demonstrated a distended gallbladder with diffuse wall thickening (Figure 1B). The mass-like focus was less conspicuous but appeared to arise from the gallbladder wall, 1
Northwestern Memorial Hospital, Chicago, IL, USA University of Illinois at Chicago, IL, USA
2
Case Report Clinical Presentation A 59-year-old male presented with a 3-day history of episodic right upper quadrant pain accompanied by nausea.
Corresponding Author: Guang-Yu Yang, Department of Pathology, Northwestern University, Feinberg School of Medicine, 303 E Chicago Ave, Ward 4-176, Chicago, IL 60611, USA. Email: [email protected]
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
410
International Journal of Surgical Pathology 23(5)
Figure 1. Sonographic and computed tomography imaging of the gallbladder.
Ultrasound of the gallbladder (longitudinal view) shows a distended gallbladder with abnormal wall thickening (yellow asterisks), some sludge (blue arrow) with no definitive gallstones, and a focal mass-like heterogeneous area (red arrowheads) inseparable from the gallbladder wall and adjacent liver (A). Coronal images from contrast-enhanced CT demonstrate a distended gallbladder with diffuse wall thickening (blue arrow) and a mass (red arrowheads) appearing to arise from the gallbladder wall, projecting intraluminally (B). Axial CT showed an enlarged lymph node (red arrow) abutting the gallbladder (blue arrow, C).
projecting intraluminally (Figure 1B). CT imaging convincingly separated this process from the adjacent liver. Axial CT image showed an enlarged lymph node abutting the gallbladder (Figure 1C). No other lesions or masses were identified.
Pathology and Immunohistochemistry Findings Laparoscopic cholecystectomy revealed an 8.6 × 3.8 × 3.5 cm gallbladder with roughened, hemorrhagic serosa and a thickened (1.5 cm) wall (Figure 2A). The gallbladder lumen contained friable pink-tan tissue, which was adherent to the mucosa of the neck, body, fundus, and cystic duct. Histologic sections revealed infiltration of the gallbladder mucosa by a poorly differentiated neoplasm (Figure 2B). The cells were large and epithelioid and exhibited marked pleomorphism with abundant eosinophilic cytoplasm, and vesicular nuclei harboring prominent centrally located nucleoli (Figure 2C). Numerous multinucleated cells, mitoses including atypical mitotic figures, were identified (Figure 2C). Areas with significant numbers of small lymphocytes and plasma cells were noted throughout the lesion mimicking features of lymphoepithelial carcinoma (Figure 2C). Despite extensive
histologic examination, no areas of invasion into the muscularis propria were identified and the lesion was located entirely within the mucosa (low-power view; Figure 2B). There was no lymphovascular invasion or pigment production and a regional lymph node was negative for metastasis. Immunostaining revealed tumor cells to be completely negative for cytokeratin AE1/AE3 (Clone AE 1/3, Dako, Carpinteria, CA; Figure 2D), but diffusely and strongly positive for S-100 protein (Ventana, prediluted, Tucson, AZ; Figure 2E) and Sox-10 (Biocare Medical, prediluted, Concord, CA; Figure 2F) with rare cells exhibiting positivity for Melan-A (Clone A103, pre-diluted, Dako, Carpinteria, CA; data not shown). All tumor cells were negative for EBER in situ hybridization (Dako). The overall immunoprofile was consistent with a diagnosis of intramucosal melanoma. Extensive review of the clinical history revealed a remote history of primary cutaneous desmoplastic melanoma of the right anterior neck that was excised 5 years prior. Histologic evaluation revealed the Breslow depth to be 3 mm and the Clark Level V, but ulceration could not be evaluated. Morphologically, there was a dermal proliferation of dendritic and highly atypical spindle-shaped
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
411
Lo et al
Figure 2. Gross, microscopic, and immunohistochemical profile of gallbladder intramucosal metastatic melanoma.
The gallbladder lumen grossly contained friable pink-tan tissue, which was adherent to the mucosa of the neck, body, fundus, and cystic duct (A). Histologically, the poorly differentiated lesion was located entirely within the mucosa (B) with large, epithelioid, pleomorphic cells with prominent nucleoli (C). Immunohistochemically, the lesional cells were negative for cytokeratin AE1/AE3 (D), but positive for S100 (E) and Sox 10 (F).
melanocytes with pleomorphism and hyperchromasia (Figure 3A and B). These cells were imbedded in a sclerotic stroma with some myxoid features. No vascular invasion or satellitosis was identified and no lymph nodes were examined in association with this specimen. Lesional cells were negative for AE1/AE3 (Clone AE 1/3, Dako; data not shown), strongly positive for S100 (Ventana, prediluted; Figure 3C), focally positive for Melan-A (Clone A103, prediluted, Dako; data not shown), and strongly positive for Sox-10 (Biocare Medical, prediluted, Concord, CA; Figure 3D). Although the morphology of the primary cutaneous melanoma was drastically different than the gallbladder intramucosal melanoma, the immunostaining profile of both lesions was identical and intramucosal metastasis to the gallbladder was diagnosed.
Discussion Isolated metastasis of melanoma to the gallbladder or biliary tree is extremely rare with only 11 cases reported in the English literature.6 More commonly, metastasis to the gallbladder is one of a multitude of sites involved in widely metastatic disease. Five cases of isolated metastatic melanoma to the gallbladder were also reported in one study, but additional metastases were later identified in each case.6 An intramucosal isolated gallbladder metastasis has been reported in another case, but this patient later
developed widely metastatic disease.7 We report a case of isolated metastatic intramucosal melanoma to the gallbladder, which histopathologically demonstrated features mimicking lymphoepithelial carcinoma and was significantly distinct from the remote primary cutaneous melanoma. Per our clinical follow-up for 8 months after gallbladder resection, no addition metastases have been identified (data not shown). Patients with metastatic tumor in the gallbladder commonly present with cholecystitis and/or abdominal pain.8,9 In symptomatic patients, sonography is often the first utilized imaging modality because of the high accuracy in diagnosing cholelithiasis and high sensitivity for diagnosing cholecystitis.10 As seen in our case, the clinical and sonographic initial diagnosis was cholecystitis. The gross examination of the cholecystectomy specimen was correlated with the sonography and CT imaging findings and revealed a friable “mass-like” thickened mucosa involving the entire gallbladder including the gallbladder neck, body, fundus, and cystic duct. Histopathologically, an isolated gallbladder intramucosal poorly differentiated malignancy appeared as an incidental finding that was further confirmed as an extremely rare case of isolated gallbladder intramucosal metastasis of melanoma in a patient with a remote history of cutaneous melanoma. In our case, the intramucosal tumor histopathologically exhibited features mimicking lymphoepithelial carcinoma
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
412
International Journal of Surgical Pathology 23(5)
Figure 3. Histologic and immunohistochemical findings of the primary cutaneous melanoma of the anterior neck.
Low-power view shows a diffuse cell infiltrate deep to the epidermis (A) consisting of highly atypical spindle-shaped melanocytes in a background of desmoplasia (B). Immunostaining revealed lesional cells to be positive for S100 (C) and Sox-10 (D).
including pleomorphic, epitheloid neoplastic cells mixed with lymphoplasmacytic cells. Given this morphology, the main consideration in the differential diagnosis was poorly differentiated carcinoma, particularly EBERpositive lymphoepithelial carcinoma. However, negative staining for cytokeratin AE1/AE3 and EBER ruled out poorly differentiated carcinoma. Although the morphology was significantly distinct from the remote cutaneous desmoplastic melanoma with a predominantly spindle cell pattern, positive staining of S100 and SOX10 supported the diagnosis of isolated gallbladder intramucosal metastatic melanoma. It is well known that malignant melanoma has various morphologic patterns cytomorphologically and architecturally that can mimic any type of neoplastic process ranging from benign to malignant including but not limited to carcinoma, sarcoma, lymphoma, or even germ cell tumors.11 Distinct morphology of metastatic melanoma from its primary cutaneous source is also not an uncommon phenomenum.11 All of these pathologic variations cause tremendous diagnostic difficulty, particularly in cases of metastasis. Therefore, immunostaining is the most important ancillary approach to diagnose metastatic melanoma, especially in poorly differentiated tumors. Difficult
cases, like our case, which stain positively for S100 and Sox-10, solidify a diagnosis of melanoma. The diagnosis of metastatic melanoma in our case was further substantiated when we discovered the patient’s remote history of primary cutaneous melanoma excised 5 years previously. Although histologically both the primary melanoma and the intramucosal metastasis demonstrated drastically different morphology, both lacked pigment production and had identical immunohistochemical profiles, which favored a diagnosis of metastatic gallbladder intramucosal melanoma. In summary, we have documented a very rare case of isolated gallbladder intramucosal metastasis of melanoma in an adult patient with symptoms of cholecystitis and a remote history of primary cutaneous desmoplastic melanoma. Our case highlights the need for careful imaging analysis in patients with primary cutaneous melanoma, as even nonspecific changes identified may represent metastatic disease. Our case further demonstrates the importance of a broad differential diagnosis in evaluation of cases of poorly differentiated gallbladder tumors and emphasizes the importance of a clear clinical history and need for immunostaining to help deliver a definitive diagnosis.
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
413
Lo et al Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Vernadakis S, Rallis G, Danias N, et al. Metastatic melanoma of the gallbladder: an unusual clinical presentation of acute cholecystitis. World J Gastroenterol. 2009;15:3434-3436. 2. Velez AF, Penetrante RB, Spellman JE Jr, Orozco A, Karakousis CP. Malignant melanoma of the gallbladder: report of a case and review of the literature. Am Surg. 1995;61:1095-1098. 3. Crippa S, Bovo G, Romano F, Mussi C, Uggeri F. Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature. Melanoma Res. 2004;14:427-430. 4. Dasgupta TK, Brasfield RD. Metastatic melanoma of the gastrointestinal tract. Arch Surg. 1964;88:969-973.
5. Cellerino P, Corsi F, Morandi E, Foschi D, Trabucchi E. Metastatic melanoma of the gallbladder. Eur J Surg Oncol. 2000;26:815-816. 6. Katz RI, Cimino L, Vitkun SA. Preoperative medical consultations: impact on perioperative management and surgical outcome. Can J Anaesth. 2005;52:697-702. 7. Samplaski MK, Rosato EL, Witkiewicz AK, Mastrangelo MJ, Berger AC. Malignant melanoma of the gallbladder: a report of two cases and review of the literature. J Gastrointest Surg. 2008;12:1123-1126. 8. Langley RG, Bailey EM, Sober AJ. Acute cholecystitis from metastatic melanoma to the gall-bladder in a patient with a low-risk melanoma. Br J Dermatol. 1997;136: 279-282. 9. Dong XD, DeMatos P, Prieto VG, Seigler HF. Melanoma of the gallbladder: a review of cases seen at Duke University Medical Center. Cancer. 1999;85:32-39. 10. Anderson JC, Harned RK. Gray scale ultrasonography of the gallbladder: an evaluation of accuracy and report of additional ultrasound signs. AJR Am J Roentgenol. 1977;129:975-977. 11. Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma. Histopathology. 2000;36:387-402.
Downloaded from ijs.sagepub.com at UNIV CALIFORNIA SAN DIEGO on November 16, 2015
