Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 447
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

  Table of Contents    
Year : 2013  |  Volume : 56  |  Issue : 2  |  Page : 172-175
Cytokeratin-positive interstitial reticulum cell sarcoma: Extranodal presentations mimicking carcinoma

1 Department of Pathology, Cancer Institute (W.I.A.), 38, Sardar Patel Road, Chennai, Tamil nadu, India
2 Department of Surgical Oncology, Cancer Institute (W.I.A.), 38, Sardar Patel Road, Chennai, Tamil nadu, India

Click here for correspondence address and email

Date of Web Publication23-Sep-2013


Cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma is a rare type of dendritic cell tumor derived from a subset of fibroblastic reticular cells. Expression of cytokeratins and extranodal location of these tumors can lead to a misdiagnosis of carcinoma. We report two cases of CIRC sarcomas primarily involving the scalp and breast. Patients were referred with an initial diagnosis of carcinoma. Case 1 underwent wide local excision of the scalp tumor with left posterolateral neck dissection. Case 2 had modified radical mastectomy for the tumor in left breast. Histopathological examination of both specimens showed an epithelioid to spindle cell malignant tumor that co-expressed CK 8, CK 18, vimentin, and smooth muscle actin. A diagnosis of CIRC sarcoma was made. Pathologists should be aware of this subset of dendritic cell sarcoma. Carcinomas, other sarcomas of the accessory dendritic cell family, and poorly differentiated malignant tumors have to be ruled out by combination of morphology, immunohistochemistry, and electron microscopic studies.

Keywords: Breast, cytokeratin-positive interstitial reticulum cell sarcoma, extranodal, scalp

How to cite this article:
Sundersingh S, Majhi U, Krishnamurthy A, Velusami SD. Cytokeratin-positive interstitial reticulum cell sarcoma: Extranodal presentations mimicking carcinoma. Indian J Pathol Microbiol 2013;56:172-5

How to cite this URL:
Sundersingh S, Majhi U, Krishnamurthy A, Velusami SD. Cytokeratin-positive interstitial reticulum cell sarcoma: Extranodal presentations mimicking carcinoma. Indian J Pathol Microbiol [serial online] 2013 [cited 2021 Oct 25];56:172-5. Available from: https://www.ijpmonline.org/text.asp?2013/56/2/172/118689

   Introduction Top

Accessory dendritic/reticulum cells in the lymph nodes are comprised of follicular dendritic cells (FDCs), interdigitating dendritic cells (IDCs), Langerhan's cells (LCs), and fibroblastic reticular cells (FRCs). Cytokeratin-positive interstitial reticulum cells (CIRCs) are a subset of FRCs. [1] While tumors derived from the first three cell types are well-recognized and reported; tumors derived from FRCs are uncommon, and those of CIRC origin are even more rare. This is attributed either to the lack of awareness of these tumors or their expression of cytokeratins leading to a misdiagnosis of carcinoma, particularly when they are of nodal origin, which is more often the case. Cytokeratin-positive interstitial reticulum cells were first described by Franke and Moll [2] in the year 1987. These cells considered to be indigenous to lymphoid organs, originate from mesenchymal stem cells. They have long slender cytoplasmic processes extending between lymphocytes and are found in the extrafollicular compartment, paracortex and medulla of lymph nodes, spleen and tonsils. They express cytokeratin 8 and 18 with some of them co-expressing smooth muscle actin (SMA) (20-60%) and desmin (1-10%). Tumors arising from CIRCs were first documented by Gould et al. [3] Altogether, 12 cases of CIRC tumors have been reported in the literature. [3],[4],[5],[6],[7],[8],[9],[10] Except for one case where tumor was located in the soft tissue, [4] remaining tumors were of nodal origin. Two additional cases of extranodal CIRC sarcomas, primarily involving the scalp and breast, are presented here for the first time in literature.

   Case Reports Top

Case 1

A 64-yrs-old gentleman complained of swelling in the scalp of 20 yrs duration. There was an increase in the size of the swelling associated with pain for the past 3 months and a swelling in the back of his neck of 1-month duration. A biopsy of the posterior cervical lymph node done at another hospital was reported as metastatic carcinoma. He was referred to our institute for further management. Local examination revealed a swelling in the left parieto-occipital region, arising from the scalp. There was discoloration of the overlying skin. The swelling was non-tender, measuring 3 × 2.5 cm, firm, and freely mobile over the underlying structures. Examination of the neck on the left side showed a transverse scar at level 5 with underlying induration. Palpation of the neck revealed a firm sub-centimeter lymph node in the left sub-occipital triangle. No other lymph nodes were palpable. Computed tomography scan of the scalp showed a highly vascular lesion in the parieto-occipital region supplied by the occipital and posterior auricular branches of the posterior carotid artery. No intracranial SOL was seen. The slides of the lymph node biopsy done outside were reviewed, and in view of the epithelioid appearance of tumor cells, a diagnosis of metastatic poorly differentiated carcinoma was made. Wide local excision of the scalp tumor with left postero-lateral neck dissection was done. Gross examination of the scalp specimen showed a grey-white, firm tumor measuring 3 × 2.5 × 1 cm. Histopathological examination showed ill-defined tumor nodules in the dermis of the skin [Figure 1]a composed of dense collections of lymphocytes, plasma cells, and scattered plump, oval to elongated cells with moderate eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli in the background, arranged in fascicles and sheets [Figure 1]b. Mitoses were 7-9/10 hpf. Immunohistochemistry showed positive reaction of the plump cells for cytokeratin in a dendritic manner [Figure 1]c, vimentin and negative reaction for CD45, CD20, CD3, CD43, CD30, EMA, Alk 1, HMB45, S100 P, CD31, and CD34. Scattered histiocytoid cells were positive for CD68. Ki 67 index was 40%. Following the dendritic pattern of cytokeratin positivity, an additional panel of immunohistochemistry markers was done. The tumor cells were positive for CK8, CK 18 [Figure 1]d and e, SMA and negative for desmin, CD21, CD23, and CD35. Scattered tumor cells also showed positive reaction for p53. One left level 2B lymph node measuring 0.8 cm across showed metastatic tumor with a more epithelioid histology [Figure 1]f and immunohistochemical features similar to the scalp tumor. A diagnosis of CIRC sarcoma of scalp metastatic to lymph node was made. This patient received adjuvant radiotherapy of 55 Gy in 180 cGy per fraction over 5.5 weeks to the scalp and left neck, using a combination of electrons and photons. He subsequently died of brain metastasis 10 months following surgery.
Figure 1: (a) Scalp tumor showing ill-defined tumor nodules in the dermis of the skin (H and E, x40). (b) Higher power showing fascicles and sheets of plump oval to spindle cells in a background of dense collections of lymphocytes and plasma cells (H and E, x200). (c,d,e) Immunohistochemistry of scalp tumor showing positive reaction of plump cells for cytokeratin (CK), CK 8 and CK 18 in a dendritic manner (DAB, x200). (f) Lymph node showing metastatic tumor with an epithelioid histology (H and E, x200)

Click here to view

Case 2

A 45-yrs-old female was referred with a lump in her left breast of 2 months duration. She had undergone biopsy outside, which was reported as infiltrating duct carcinoma, grade 3. On examination, there was a large, firm tumor occupying the upper inner quadrant and central sector of the left breast. There were no enlarged lymph nodes. Ultrasonography of the left breast showed a solid nodule in the upper inner quadrant and central sector. The slides of the biopsy done earlier was reviewed and reported as poorly differentiated malignant tumor. Patient underwent a left modified radical mastectomy. Gross examination of the mastectomy specimen showed a circumscribed, pink, fleshy tumor, measuring 6 × 6 × 6 cm, involving the upper inner quadrant and central sector of the left breast [Figure 2]a. Histopathological examination showed a tumor composed of sheets and fascicles of round oval to fusiform and epithelioid cells with moderate cytoplasm and irregular vesicular nuclei with prominent nucleoli exhibiting moderate nuclear pleomorphism. Scattered lymphoid cells were seen amidst the tumor cells [Figure 2]b. Mitoses were 10-12/10 hpf. Areas of necrosis and degeneration were seen. Axillary lymph nodes were free. Immunohistochemistry showed positive reaction of the tumor cells for CK8, CK18, vimentin, SMA [Figure 2]c-f and negative for desmin, Alk1, CD21, CD23, CD35, CD68, and S100 P. Most tumor cells showed strong positivity for p53, and Ki67 index was 80-90%. ER, PR was negative. A diagnosis of CIRC sarcoma was made. This patient received adjuvant radiotherapy of 50 Gy in 180 cGy per fraction over 5 weeks to the left side chest wall, using medial and lateral tangential fields with 6 Mv photons. She was offered CHOP chemotherapy but declined it and died of metastatic disease 14 months following surgery.
Figure 2: (a) Mastectomy specimen showing a circumscribed, pink, fleshy tumor of the breast. (b) Breast tumor showing sheets of oval to epithelioid cells with irregular vesicular nuclei and prominent nucleoli admixed with scattered lymphoplasmacytoid cells (H and E x200). (c,d,e,f) Immunohistochemistry of breast tumor showing positive reaction of neoplastic cells for CK 8, CK18, vimentin and SMA (DAB, x200)

Click here to view

   Discussion Top

Cytokeratin-positive interstitial reticulum cells (CIRCs) are found in variable numbers and distribution in normal lymph nodes, spleen and tonsil. The etiology of CIRC sarcoma remains speculative. Gould et al.[11] described an increased number of CIRCs in lymphadenopathy associated with various conditions as a result of hyperplasia-like response or CK 8/18 gene induction. This process has the potential capability to undergo dysplastic changes and eventually malignant transformation, giving rise to tumors with features similar to carcinomas. Fibroblastic reticular cells (FRCs) play a role in maintaining the integrity of lymph nodes, production and transport of cytokines and other mediators. High levels of IL-6 and VEGF were detected in supernatant from primary culture of a recurrent CIRC sarcoma, confirmed by immunostaining of sections with IL-6 and VEGF. [5] Increased p53 expression was observed in metastatic and relapsed tumors, and hence a role for p53 in the malignant transformation of these tumors suggested. [5],[7] No viral etiology has been established in these so far.

Grossly, the tumors have a homogenous, tan, nodular appearance. Microscopically, ill-defined fascicles and sheets of non-cohesive oval to spindle cells with ill-defined cytoplasmic border, elongated to ovoid vesicular nuclei with distinct nucleoli exhibiting mild to moderate nuclear atypia admixed with a rich reactive lymphoplasmacytic infiltrate is seen. Necrosis may be present. Mitosis varies from 2-7/10 hpf. Immunohistochemistry shows co-expression of the tumor cells for keratin and vimentin. Cytokeratin highlights the elongated cytoplasmic process of tumor cells. Desmin and SMA can also be co-expressed. Dendritic cell markers are negative. Electron microscopy shows slender cytoplasmic interdigitating projections and desmosome-like junctions between the tumor cells corresponding to the expression of cytokeratins and rich intermediate filaments and tonofilament-like tight bundles/dense bodies in the cytoplasm corresponding to the expression of vimentin and SMA. These findings suggest that CIRCs originate from mesenchymal stem cells that show bi-directional differentiation towards epithelioid and myoid/myofibroblastic cells. [8]

CIRC sarcomas need to be distinguished from carcinomas, tumors derived from other accessory dendritic cells, myofibroblasts, and poorly differentiated malignant tumors. CIRC sarcomas have no characteristic clinical symptoms or histological features. These tumors with an epithelioid morphology can be misdiagnosed as carcinomas. The characteristic elongated reticulum shape of the tumor cells exhibiting a dendritic pattern of cytokeratin positivity helps in distinguishing them from carcinomas. Carcinomas, on the other hand, usually exhibit a greater degree of nuclear atypia, increased mitosis, and complete epithelial characteristics under electron microscopy. Metastatic carcinomas have primary sites, and EBV infection is detected in lymphoepithelial carcinoma. Langerhan's cell sarcoma consistently expresses S100 protein and CD1a. Interdigitating dendritic cell sarcoma expresses S100 protein and is weakly positive for CD 68, lysozyme, and CD 45. Follicular dendritic cell sarcomas, although at instances do express cytokeratin, are strongly positive for one or more of the follicular dendritic cell markers like CD 21, CD 23, and CD 35. Histiocytic sarcomas express CD 68 and CD 163. Inflammatory myofibroblastic tumors are positive for Alk1 and desmin. Cytokeratin may be positive in some inflammatory myofibroblastic tumors, and the difficulty in distinguishing a CIRC tumor from a cytokeratin-positive and desmin-negative inflammatory myofibroblastic tumor suggest a close relationship between the two entities, which might be included in the same tumor spectrum, with inflammatory myofibroblastic tumors representing the low-grade and CIRC sarcomas representing the high-grade version of the tumor. Negative immunostaining for CD30, EMA, Alk1, HMB45, and S100 P can help in distinguishing anaplastic large cell lymphoma and malignant melanoma.

Surgical excision is the primary mode of treatment. The role of adjuvant chemotherapy and radiotherapy is not clearly defined. In non-metastatic tumors, surgery alone or surgery followed by adjuvant radiotherapy is recommended for prolonged survival; [3] however, its efficacy in metastatic cases is questionable. Prognosis of CIRC sarcomas is difficult to establish due to its variable biologic behavior and limited number of cases. However, increased nuclear atypia, increased mitosis, and presence of necrosis was associated with an aggressive behavior, and patients died of distant metastasis. [5],[7] These tumors might benefit from chemotherapy/radiotherapy to prevent distant metastasis and extend the life span. The use of targeted therapy like antibodies or inhibitors of IL-6 and VEGF, which are highly expressed by these tumor cells, may also be considered in an adjuvant setting. [8]

   References Top

1.Jaffe R, Pileri SA, Facchetti F, Jones DM, Jaffe ES. Histiocytic and dendritic cell neoplasms, Introduction. In: Swerdlow SH, Campo E, Harris NL, et al, editors. WHO Classification of Tumours of Haematopoeitic and Lymphoid Tissues. Lyon: IARC Press; 2008. p. 354-5.  Back to cited text no. 1
2.Franke WW, Moll R. Cytoskeletal components of lymphoid organs. I. Synthesis of cytokeratins 8 and 18 and desmin in subpopulations of extrafollicular reticulum cells of human lymph nodes, tonsils, and spleen. Differentiation 1987;36:145-6.  Back to cited text no. 2
3.Gould VE, Warren WH, Faber LP, Kuhn C, Franke WW. Malignant cells of epithelial phenotype limited to thoracic lymph nodes. Eur J Cancer 1990;26:1121-6.  Back to cited text no. 3
4.Chan AC, Serrano-Olmo J, Erlandson RA, Rosai J. Cytokeratin-positive malignant tumors with reticulum cell morphology: A subtype of fibroblastic reticulum cell neoplasm? Am J Surg Pathol 2000;24:107-16.  Back to cited text no. 4
5.Kakiuchi C, Ishida T, Sato H, Katano H, Ishiko T, Mukai H, et al. Secretion of interleukin-6 and vascular endothelial growth factor by spindle cell sarcoma complicating Castleman's disease (so-called 'vascular neoplasia'). J Pathol 2002;197:264-71.  Back to cited text no. 5
6.Schuerfeld K, Lazzi S, De Santi MM, Gozzetti A, Leoncini L, Pileri SA. Cytokeratin-positive interstitial cell neoplasm: A case report and classification issues. Histopathology 2003;43:491-4.  Back to cited text no. 6
7.Lucioni M, Boveri E, Rosso R, Benazzo M, Necchi V, Danova M, et al. Lymph node reticulum cell neoplasm with progression into cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma: A case study. Histopathology 2003;43:583-91.  Back to cited text no. 7
8.Dong YC, Wu B, Sheng Z, Wang JD, Zhou HB, Zhou XJ. Cytokeratin-positive interstitial reticulum cell tumors of lymph nodes: A case report and review of literature. Chin Med J (Engl) 2008;121:658-63.  Back to cited text no. 8
9.Kwon JE, Yang WI, Kim HK, Kwon KW, Kwon TJ, Choi EC, et al. Cytokeratin-positive interstitial reticulum cell sarcoma: A case report with cytological, immunohistochemical, and ultrastructural findings. Cytopathology 2009;20:202-5.  Back to cited text no. 9
10.Suárez D, Izquierdo FM, Méndez JR, Escobar J, Cabeza A, Junco P. Tumor of fibroblastic reticular cells of lymph node coincidental with an undifferentiated endometrial stromal sarcoma. Report of a case with distinctive immunophenotype and Kikuchi-like necro-inflammatory response. APMIS 2011;119:216-20.  Back to cited text no. 10
11.Gould VE, Bloom KJ, Franke WW, Warren WH, Moll R. Increased numbers of cytokeratin-positive interstitial reticulum cells in reactive, inflammatory and neoplastic lymphadenopathies: Hyperplasia or induced expression? Virchows Arch 1995;425:617-29.  Back to cited text no. 11

Correspondence Address:
Shirley Sundersingh
New No.23, Jambulingam Street, Nungambakkam, Chennai - 600 034, Tamil nadu
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.118689

Rights and Permissions


  [Figure 1], [Figure 2]

This article has been cited by
1 Fibroblastic Reticulum Cell Tumor of the Breast: A Case Report and Review of Literature
Priya Iyer,Shirley Sundersingh,E. Venkatesan,Balasubramanian Ananthi,Ganesarajah Selvaluxmy,Venkatraman Radhakrishnan
Indian Journal of Gynecologic Oncology. 2017; 15(3)
[Pubmed] | [DOI]
2 Fibroblastic reticular cell tumor of the breast: A case report and review of the literature
Experimental and Therapeutic Medicine. 2016; 11(2): 561
[Pubmed] | [DOI]
3 A Rare Case of Cytokeratin-Positive Interstitial Reticulum Cell Sarcoma and Review of the Entity
Shravasti Roy,Indranil Das,Kaushik Saha,Rakesh Roy,Sumanta Bhattacharya
Indian Journal of Surgical Oncology. 2015;
[Pubmed] | [DOI]
4 A Rare Case of Follicular Dendritic Cell Sarcoma with Pseudochylous Effusion and Review of Literature From India
Kamal Kant Sahu,Gaurav Prakash,Sandeep Rao,Amanjit Bal,Pankaj Malhotra,Jasmina Ahluwalia,Rakesh K. Vashistha
Indian Journal of Hematology and Blood Transfusion. 2014;
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Reports
    Article Figures

 Article Access Statistics
    PDF Downloaded122    
    Comments [Add]    
    Cited by others 4    

Recommend this journal