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Mesothelial cell deposits in lymph nodes—a diagnostic pitfall
Annals of Diagnostic Pathology 25 (2016) 31–32
Contents lists available at ScienceDirect
Annals of Diagnostic Pathology
Letter to the Editor
Mesothelial cell deposits in lymph nodes—a diagnostic pitfall☆ Sir, Finding epithelioid keratin-positive cells in a lymph node poses little, if any, diagnostic challenge in a patient with known carcinoma. The same finding in a patient with no history of cancer raises a possibility of metastasis from unknown primary. Seeking an alternative explanation is critical, as the ramifications of the decisions in this situation are profound: stage IV malignancy vs benign. The lymph nodes filter the lymphatic fluid and can trap both benign and malignant cells. Among the benign cells, most common inclusions are nevus cells [1,2], glandular inclusions [3], decidua [4], salivary gland epithelium [5], benign breast epithelium [6], thyroid tissue [7], and rarely mesothelial cells [8]. We report a case of benign mesothelial cells present in a thoracic lymph node. A 25-year-old man presented to the hospital after sustaining a penetrating left chest wall injury between the third and fourth intercostal space. He developed mild pericardial effusion without any pneumothorax. Exploratory sternotomy was performed to repair the defect. A 15mm lymph node present adjacent to the left mammary artery was sent to histology because it appeared slightly enlarged. The histology revealed that most of the lymph node was replaced by sheets of relatively large epithelial cells spreading into the subcortical sinuses (Fig. 1A and B). These cells showed mild degree of nuclear pleomorphism with eosinophilic cytoplasm and relatively low nuclear to cytoplasmic ratio. There were rare (b1 per 10 high-power field) mitoses. Based on the histological features, a benign process, such as sinus histiocytosis, was suspected. As an alternative, a remote possibility of metastatic melanoma, carcinoma, and germ cell tumor was considered. The first panel of immunohistochemistry showed the tumor cells positive for cytokeratin CKAE1/3 (Fig. 1C) and negative for S100, Melan A, HMB45, CD30, CD45, OCT-4, and CD68. Another panel was requested, and the tumor cells revealed strong positivity for WT1 (Fig. 1D) and calretinin demonstrating mesothelial origin. The features were those of benign mesothelial cell deposits based on the clinical presentation and radiological absence of malignancy. The patient was followed up and subsequently discharged. He remains asymptomatic 6 months past surgery. (See Fig. 2.) Nodal inclusions were first described in 1897 by Ries [1]. Since that time, different benign inclusions have been described by various authors falling into 3 main groups: epithelial, nevus, and decidual, although leiomyomatosis [9] and lipomatosis [10] have also been described. The common sites are pelvic, axillary, mediastinal, paraaortic, and cervical lymph nodes [1-11]. On occasion, malignancy can arise from these benign inclusions [7]. Benign mesothelial cells involving mediastinal lymph nodes were originally described by Brooks et al in 1990 [11]. The authors described mesothelial “inclusions” in 2 patients with pleuritis and pleural ☆ Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose. 1092-9134/© 2016 Elsevier Inc. All rights reserved.
effusions. As in our case, that paper described a dilemma, where malignant diagnosis was considered based on morphology and cytokeratin positivity. In general, CKAE1/3-positive cells in a thoracic lymph node may represent metastatic carcinoma, metastatic mesothelioma, or benign mesothelial cell inclusions. In our case, we concluded that the latter is the most logical diagnosis based on hematoxylin and eosin (H&E) morphology, WT1, calretinin positivity, and the absence of clinical or radiographic evidence of malignancy. The history of recent injury to chest wall provides a logical explanation for the presence of these cells. Actual mechanism of the mesothelial cell deposition in the lymph nodes is not fully understood; however, transport of these cells through the lymphatics to the lymph node in patients with pleural effusion secondary to injury or manipulation is the prevailing theory, confirmed previously on several occasions [11]. Pleural or peritoneal effusions are documented in a vast majority of the cases of benign nodal mesothelial inclusions. It is the most likely mechanism in our case. It is important to recognize this rare and unique phenomenon, as it can be easily misdiagnosed as metastatic carcinoma of unknown primary. It is therefore recommended that any patient with this finding be evaluated thoroughly, using readily available immunohistochemical studies including WT-1 and calretinin, to avoid misdiagnosis and subsequent consequences. Archana Pandita* Vladimir Osipov Department of Anatomic Pathology Wellington Regional Hospital, New Zealand *Corresponding author E-mail address: [email protected]
http://dx.doi.org/10.1016/j.anndiagpath.2016.08.006 References [1] Amrani M, Jahid A, et al. Benign nevus cell inclusions in two patients treated for cancer. Ann Pathol 2002;22(4):321–3. [2] Holt JB, Sangueza OP, et al. Nodal melanocytic nevi in sentinel lymph nodes. Correlation with melanoma-associated cutaneous nevi. Am J Clin Pathol 2004;121(1):58–63. [3] Maaben V, Hiller K. Glandular inclusions in lymph nodes. Pattern of distribution and metaplastic transformation. Arch Gynecol Obstet 1994;255:1–8. [4] Wu DC, Sharon H, et al. Ectopic decidua of pelvic lymph nodes, a Petential diagnostic pitfall. Arch Pathol Lab Med 2005;129. [5] Lewis AL, Truong LD, et al. Benign salivary gland tissue inclusion in a pulmonary hilar lymph node from a patient with invasive well differentiated adenocarcinoma of the lung: a potential misinterpretation for the staging of carcinoma. Int J Surg Pathol 2011;19(3):382–5. [6] Chuang C, Hicks DG. Benign inclusion of axillary lymph nodes: report of two cases and literature review. Breast J 2009;15(6):664–5. [7] Ayumi N, Keiko N, et al. Primary papillary carcinoma arising from ectopic thyroid tissue in the cervical lymph nodes: a case report. J Oral Maxillofac Surg, Med Pathol 2015;27(2):240–4. [8] Peng L, Shen Q, et al. Diffuse hyperplastic mesothelial cells in multiple lymph nodes; case report with review of literature. Int J Clin Exp Pathol 2013;6(5):926–31.
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Correspondence / Annals of Diagnostic Pathology 25 (2016) 31–32
Fig. 1. (A) Epithelioid cells in a lymph node, H&E, 40× magnification. (B) Higher-power view of these cells, H&E, 100×. (C) Cytokeratin CKAE1/3, 40×. Calretinin produced similar strong immunoreactivity. (D) WT-1, 40×.
[9] Yoon G, Kim T-J, et al. Benign metastasizing leiomyoma with multiple lymph node metastasis: a case report. Cancer Res Treat 2011;43(2):131–3. [10] Karaosmanoglu AF, Blake MA, et al. Abundant macroscopic fat in intraabdominal lymph nodes involved in the course of a patient with chronic
Fig. 2. Epithelioid cells with low nuclear to cytoplasmic ratio, open nuclear chromatin, rare nucleoli, mild nuclear pleomorphism, and occasional mitoses. H&E, 400× magnification.
lymphocytic leukemia: presentation of imaging findings with biopsy correlation. Br J Radiol 2012;85(1012). [11] Brooks JS, LiVolsi VA, Pietra GG, Am J. Mesothelial cell inclusions in mediastinal lymph nodes mimicking metastatic carcinoma. Clin Pathol 1990;93(6):741–8.
Contents lists available at ScienceDirect
Annals of Diagnostic Pathology
Letter to the Editor
Mesothelial cell deposits in lymph nodes—a diagnostic pitfall☆ Sir, Finding epithelioid keratin-positive cells in a lymph node poses little, if any, diagnostic challenge in a patient with known carcinoma. The same finding in a patient with no history of cancer raises a possibility of metastasis from unknown primary. Seeking an alternative explanation is critical, as the ramifications of the decisions in this situation are profound: stage IV malignancy vs benign. The lymph nodes filter the lymphatic fluid and can trap both benign and malignant cells. Among the benign cells, most common inclusions are nevus cells [1,2], glandular inclusions [3], decidua [4], salivary gland epithelium [5], benign breast epithelium [6], thyroid tissue [7], and rarely mesothelial cells [8]. We report a case of benign mesothelial cells present in a thoracic lymph node. A 25-year-old man presented to the hospital after sustaining a penetrating left chest wall injury between the third and fourth intercostal space. He developed mild pericardial effusion without any pneumothorax. Exploratory sternotomy was performed to repair the defect. A 15mm lymph node present adjacent to the left mammary artery was sent to histology because it appeared slightly enlarged. The histology revealed that most of the lymph node was replaced by sheets of relatively large epithelial cells spreading into the subcortical sinuses (Fig. 1A and B). These cells showed mild degree of nuclear pleomorphism with eosinophilic cytoplasm and relatively low nuclear to cytoplasmic ratio. There were rare (b1 per 10 high-power field) mitoses. Based on the histological features, a benign process, such as sinus histiocytosis, was suspected. As an alternative, a remote possibility of metastatic melanoma, carcinoma, and germ cell tumor was considered. The first panel of immunohistochemistry showed the tumor cells positive for cytokeratin CKAE1/3 (Fig. 1C) and negative for S100, Melan A, HMB45, CD30, CD45, OCT-4, and CD68. Another panel was requested, and the tumor cells revealed strong positivity for WT1 (Fig. 1D) and calretinin demonstrating mesothelial origin. The features were those of benign mesothelial cell deposits based on the clinical presentation and radiological absence of malignancy. The patient was followed up and subsequently discharged. He remains asymptomatic 6 months past surgery. (See Fig. 2.) Nodal inclusions were first described in 1897 by Ries [1]. Since that time, different benign inclusions have been described by various authors falling into 3 main groups: epithelial, nevus, and decidual, although leiomyomatosis [9] and lipomatosis [10] have also been described. The common sites are pelvic, axillary, mediastinal, paraaortic, and cervical lymph nodes [1-11]. On occasion, malignancy can arise from these benign inclusions [7]. Benign mesothelial cells involving mediastinal lymph nodes were originally described by Brooks et al in 1990 [11]. The authors described mesothelial “inclusions” in 2 patients with pleuritis and pleural ☆ Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose. 1092-9134/© 2016 Elsevier Inc. All rights reserved.
effusions. As in our case, that paper described a dilemma, where malignant diagnosis was considered based on morphology and cytokeratin positivity. In general, CKAE1/3-positive cells in a thoracic lymph node may represent metastatic carcinoma, metastatic mesothelioma, or benign mesothelial cell inclusions. In our case, we concluded that the latter is the most logical diagnosis based on hematoxylin and eosin (H&E) morphology, WT1, calretinin positivity, and the absence of clinical or radiographic evidence of malignancy. The history of recent injury to chest wall provides a logical explanation for the presence of these cells. Actual mechanism of the mesothelial cell deposition in the lymph nodes is not fully understood; however, transport of these cells through the lymphatics to the lymph node in patients with pleural effusion secondary to injury or manipulation is the prevailing theory, confirmed previously on several occasions [11]. Pleural or peritoneal effusions are documented in a vast majority of the cases of benign nodal mesothelial inclusions. It is the most likely mechanism in our case. It is important to recognize this rare and unique phenomenon, as it can be easily misdiagnosed as metastatic carcinoma of unknown primary. It is therefore recommended that any patient with this finding be evaluated thoroughly, using readily available immunohistochemical studies including WT-1 and calretinin, to avoid misdiagnosis and subsequent consequences. Archana Pandita* Vladimir Osipov Department of Anatomic Pathology Wellington Regional Hospital, New Zealand *Corresponding author E-mail address: [email protected]
http://dx.doi.org/10.1016/j.anndiagpath.2016.08.006 References [1] Amrani M, Jahid A, et al. Benign nevus cell inclusions in two patients treated for cancer. Ann Pathol 2002;22(4):321–3. [2] Holt JB, Sangueza OP, et al. Nodal melanocytic nevi in sentinel lymph nodes. Correlation with melanoma-associated cutaneous nevi. Am J Clin Pathol 2004;121(1):58–63. [3] Maaben V, Hiller K. Glandular inclusions in lymph nodes. Pattern of distribution and metaplastic transformation. Arch Gynecol Obstet 1994;255:1–8. [4] Wu DC, Sharon H, et al. Ectopic decidua of pelvic lymph nodes, a Petential diagnostic pitfall. Arch Pathol Lab Med 2005;129. [5] Lewis AL, Truong LD, et al. Benign salivary gland tissue inclusion in a pulmonary hilar lymph node from a patient with invasive well differentiated adenocarcinoma of the lung: a potential misinterpretation for the staging of carcinoma. Int J Surg Pathol 2011;19(3):382–5. [6] Chuang C, Hicks DG. Benign inclusion of axillary lymph nodes: report of two cases and literature review. Breast J 2009;15(6):664–5. [7] Ayumi N, Keiko N, et al. Primary papillary carcinoma arising from ectopic thyroid tissue in the cervical lymph nodes: a case report. J Oral Maxillofac Surg, Med Pathol 2015;27(2):240–4. [8] Peng L, Shen Q, et al. Diffuse hyperplastic mesothelial cells in multiple lymph nodes; case report with review of literature. Int J Clin Exp Pathol 2013;6(5):926–31.
32
Correspondence / Annals of Diagnostic Pathology 25 (2016) 31–32
Fig. 1. (A) Epithelioid cells in a lymph node, H&E, 40× magnification. (B) Higher-power view of these cells, H&E, 100×. (C) Cytokeratin CKAE1/3, 40×. Calretinin produced similar strong immunoreactivity. (D) WT-1, 40×.
[9] Yoon G, Kim T-J, et al. Benign metastasizing leiomyoma with multiple lymph node metastasis: a case report. Cancer Res Treat 2011;43(2):131–3. [10] Karaosmanoglu AF, Blake MA, et al. Abundant macroscopic fat in intraabdominal lymph nodes involved in the course of a patient with chronic
Fig. 2. Epithelioid cells with low nuclear to cytoplasmic ratio, open nuclear chromatin, rare nucleoli, mild nuclear pleomorphism, and occasional mitoses. H&E, 400× magnification.
lymphocytic leukemia: presentation of imaging findings with biopsy correlation. Br J Radiol 2012;85(1012). [11] Brooks JS, LiVolsi VA, Pietra GG, Am J. Mesothelial cell inclusions in mediastinal lymph nodes mimicking metastatic carcinoma. Clin Pathol 1990;93(6):741–8.