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Primary Endobronchial Histiocytic Sarcoma in a Case of Papillary Carcinoma Thyroid: A Complex Clinical Scenario

Aggarwal, Riti MD*; Rao, Seema MD*; Sarangi, Rathindra MS

Journal of Bronchology & Interventional Pulmonology: October 2014 - Volume 21 - Issue 4 - p 353–357
doi: 10.1097/LBR.0000000000000114
Case Reports

Histiocytic sarcoma is a rare malignant neoplasm showing histiocytic differentiation. We document a case of a 55-year-old man presenting with cough and breathlessness following a subtotal thyroidectomy for infiltrating papillary thyroid carcinoma. An endobronchial growth was seen on endoscopy. Histopathologic examination revealed a neoplasm of histiocytic lineage with positivity for leucocyte common antigen, Vimentin, CD68, CD4, and CD45RO. To the best of our knowledge, primary endobronchial histiocytic sarcoma in association with infiltrating papillary thyroid carcinoma has not been reported in the literature so far. Our case emphasizes the importance of clinicopathologic and radiologic correlation in resolving difficult diagnostic dilemmas.

Departments of *Pathology

General Surgery, Sir Ganga Ram Hospital, New Delhi, India

R.A., S.R., and R.S. contributed equally.

Disclosure: There is no conflict of interest or other disclosures.

Reprints: Seema Rao, MD, Department of Pathology, Sir Ganga Ram Hospital, New Delhi 110060, India (e-mail:

Received October 3, 2013

Accepted August 13, 2014

Histiocytic sarcoma (HS) is an exceedingly rare hematolymphoid neoplasm showing morphologic and immunophenotypic features of mature histiocytes. Commonly these tumors are underrecognized because of poorly differentiated morphology and the difficulties in characterizing their histiocytic derivation. The most common site of involvement is lymph nodes; however, infrequent extranodal presentation is also known to occur. HS is also reported to manifest infrequently as a secondary neoplasm in patients with other malignancies. To our knowledge, this case represents the first case of unique association of primary endobronchial HS with papillary carcinoma of thyroid.

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In October 2012, a 55-year-old man presented with complaint of midline neck swelling, hoarseness, and difficulty in breathing. The swelling was present since 1996, contrast-enhanced computed tomography (CECT) of the neck and chest at that time revealed enlargement of the left lobe of thyroid, extending into the superior mediastinum. The trachea was shifted to the right. A hypodense lesion of 3.5×3 cm was also seen involving the right chest close to the mediastinum, most probably a benign neurogenic tumor (Fig. 1). However, he was symptomless and did not receive any treatment at that time.



In the present episode (October 2012), he had a large left-sided thyroid swelling which was extending from submandibular area to retrosternal region. On fine-needle aspiration cytology, possibility of a follicular thyroid neoplasm was suggested. On CECT, there was a heterogeneously enhancing mass arising from left lobe of thyroid, extending from angle of mandible to the arch of aorta, and compressing the trachea and the larynx. The mass was nodular in its appearance, showing areas of enhancement, necrosis, and calcification. Lung parenchyma showed multiple nodular lesions of varying sizes on both sides. There was a round enhancing lesion in the right lobe of the liver in segment VII (Figs. 2A, B).



The patient underwent total thyroidectomy. Intraoperatively, tumor was infiltrating the soft tissue near the arch of aorta and could not be shelled out completely. Therefore, a maximum possible clearance of mediastinal extension was performed.

The thyroidectomy specimen was submitted for histopathologic examination. Grossly, left lobe of thyroid with mediastinal extension measured 14×7×5 cm and right lobe was 5×2×2 cm. Cut surface of the left lobe was grey-white in color, firm with focal areas of cystic degeneration, hemorrhage, and calcification. Right lobe was unremarkable. Sections examined showed a tumor in the lobe arranged predominantly in follicular pattern along with trabecular and papillary arrangement. Lining cells had round to ovoid nuclei and pale cytoplasm. Many of the cells had ground glass nuclei. However, no nuclear grooving or pseudoinclusion was seen. The tumor was extending up to the cut margins in focal areas. Right lobe of thyroid was histologically unremarkable. Hence a final diagnosis of follicular variant of papillary carcinoma, left lobe of thyroid was given (Fig. 2C). Postoperatively, patient received radioiodine ablation therapy. Postoperative period was uneventful and he was asymptomatic for almost 3 months.

In February 2013, patient suddenly developed cough and breathlessness. There was no hepatosplenomegaly or lymphadenopathy. CECT thorax revealed a heterogeneously enhancing lesion in the left thyroid bed, infiltrating the mediastinum, although regressed in size as compared with previous scan. The mediastinal lesion was reported to be pushing the trachea to right and infiltrating and partly obstructing its lumen. Clinical and radiologic findings were suggestive of the possibility of infiltrating/metastatic papillary carcinoma thyroid (Figs. 3A, B). Right lobe of the liver lesion has regressed in size. On bronchoscopy, a nodular growth was seen arising from the right-sided tracheal wall, which was removed and tracheal stent was placed. Patient’s symptoms were relieved after the therapeutic bronchoscopy and he was discharged.



Endobronchial biopsy showed a tumor composed of large pleomorphic cells arranged in diffuse sheets. Cells were oval to polygonal with distinct cell borders and moderate to abundant eosinophilic granular cytoplasm. Nuclei were large and vesicular with prominent 1 to 2 nucleoli. Mitotic activity was high. Hemophagocytosis was noted in some of the tumor cells (Fig. 3C). The histomorphologic features were those of a high-grade poorly differentiated malignant tumor.

Various clinical and morphologic possibilities were considered and a basic panel of immunohistochemical markers was applied to determine the tumor lineage that included CK, EMA, P63, Vimentin, leucocyte common antigen (LCA), and Thyroglobulin. The first possibility considered was that the retrosternal component of thyroid tumor which was not completely removed had undergone a dedifferentiation to poorly differentiated/insular or to undifferentiated/anaplastic thyroid carcinoma. However, the tumor morphology was not characteristic of papillary, insular, or anaplastic thyroid carcinoma and negativity for Thyroglobulin, CK, and EMA ruled out this possibility. Endobronchial tumors such as non–small cell carcinomas, squamous cell carcinoma, and malignant melanoma were also ruled out as CK, P63, and HMB-45 were negative. Tumor cells showed strong positivity for Vimentin and weak positivity for LCA (Figs. 4A, B), so further hematolymphoid markers (CD3, CD20, CD30, and Alk-1; MPO, CD43, and CD138) were done to exclude T-cell/B-cell lymphoma, anaplastic large cell lymphoma, granulocytic sarcoma, and plasmacytoma, respectively. All of these markers were negative. A broad panel of markers to rule out malignant mesenchymal tumor including CD31, S-100, SMA, and Desmin were performed. Only S-100 was equivocally positive, rest were all negative.



Finally, histiocytic marker (CD68) (Fig. 4C), dendritic cell markers (Fascin), Langerhan’s cell marker (CD1a), and additional T-cell markers (CD45RO and CD4) were obtained. CD4 (Fig. 4D), CD45RO, and CD68 were focally positive, CD1a and Fascin were negative.

Reviewing all the immunohistochemical markers, a final overall positivity of the tumor cells for LCA, Vimentin, CD68, CD4, and CD45RO was diagnostic of endobronchial HS.

In the meanwhile, patient returned within 2 weeks with complaint of dyspnea. Repeat endoscopy showed recurrent endobronchial growth occluding the lumen, and stent placement was repeated for symptomatic relief. In light of a discord between clinicoradiologic possibility of infiltrating/metastatic thyroid carcinoma and a histomorphologic diagnosis of HS; radiologic images were reviewed and reassessed. It was found that the mediastinal mass present predominantly on left side and shifting the trachea to right, was not coalescent with the endobronchial mass, which was present on the right wall occluding tracheal lumen (Figs. 3A, B). The continuity of tracheal rings was maintained throughout. Hence, it was concluded that the patient had 2 different malignancies, one, papillary thyroid carcinoma with pulmonary and liver metastases and other, a primary endobronchial HS which has recently emerged and was causing respiratory symptoms in the patient at present.

Subsequently, the patient was placed on CAP regimen for lymphoma, and after receiving 5 cycles of chemotherapy, his [18F]-fluorodeoxyglucose–positron emission tomography scan showed complete regression of endobronchial lesion. After a follow-up of 6 months, patient is doing well.

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Neoplasms of histiocytes and antigen-presenting dendritic cells are extremely rare hematopoietic malignancies. The diagnostic criteria of these tumors still remain complicated and controversial due to their rarity. However, because of continually improving immunohistochemical and other diagnostic tools, there is evolution in the classification of such tumors. International Lymphoma Study Group classified histiocytic/dendritic cell neoplasms into 4 groups: (i) histiocytic sarcoma; (ii) Langerhans cell tumor; (iii) follicular dendritic cell tumor/sarcoma; and (iv)interdigitating dendritic cell tumor/sarcoma.1

HS is a malignant proliferation of cells showing histiocytic differentiation. No single immunophenotypic marker is diagnostic of HS. A comprehensive panel is necessary to make a definite lineage distinction with certainty. CD68, lysozyme, CD11C, and CD14 help to ascertain histiocytic phenotype, whereas LCA, CD45RO, and CD4 are useful in confirming the hematolymphoid nature of HS. In addition, markers of Langerhans cells (CD1a), follicular dendritic cells (Fascin) are negative.2

HS occurs most commonly in adults, equally between men and women. Both nodal and extranodal sites have been reported. The common primary extranodal sites of involvement are skin, gastrointestinal tract with few cases also reported in spleen, central nervous system, soft tissues, and lungs.1,3,4 No case of endobronchial HS has been reported so far.

Although exceedingly rare, HS is also reported to manifest as a secondary neoplasm in patients treated for acute lymphoblastic leukemia.5 The association of HS with a primary gonadal/mediastinal germ cell tumor has also been described.6 In present case, we describe the unique association of endobronchial HS with papillary carcinoma of thyroid.

HS is a rare entity with very limited published data available. Existing data are in the form of case reports or short case series and suggest that most of the cases present at a clinically advanced stage and follow an aggressive clinical course with limited response to chemotherapy.2,7 However, a subset of cases presenting with clinically localized disease may have a favorable long-term outcome. Although there are no well-established prognostic markers, Hornick et al,8 reported that tumor size may correlate with prognosis.

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Although distant metastasis of infiltrating thyroid carcinomas is well known; however, all new lesions arising in a given case need not necessarily imply metastasis. Second malignancies in thyroid carcinoma patients, although not frequent, are well documented. Therefore, in such setting, the possibility of a synchronous/metachronous second malignancy should also be considered.

The case highlights that a clear pattern can emerge within the clinical complexities if due attention is given to the clinical features and relevant investigations including radiology. A careful and thorough examination of CT scans was most useful in the present case to establish the pathologist’s view of a second malignancy. An open mind, systematic multidisciplinary approach, and comprehensive but judicious use of immunohistochemical markers can help to achieve a definite diagnosis in majority of poorly differentiated tumors. Such a clinicopathologic correlation is important to avoid the possibility of overlooking a new second malignancy which may prove critical for further management and prognosis.

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1. Pileri SA, Grogan TM, Harris NL, et al.. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology. 2002;41:1–29.
2. Swerdlow SH, Campo E, Harris NL, et al.. Pathology and Genetics of Tumors of Hematopoietic and Lymphoid Tissues. 2008.Lyon, France:IARC PressWorld Health Organisation Classification of Tumours.
3. Alvaro T, Bosch R, Salvado MT, et al.. True histiocytic lymphoma of the stomach associated with low-grade B-cell mucosa-associated lymphoid tissue (MALT)-type lymphoma. Am J Surg Pathol. 1996;20:1406–1411.
4. Sun W, Nordberg ML, Fowler MR. Histiocytic sarcoma involving the central nervous system: clinical, immunohistochemical, and molecular genetic studies of a case with review of the literature. Am J Surg Pathol. 2003;27:258–265.
5. Wongchanchailert M, Laosombat V. True histiocytic lymphoma following acute lymphoblastic leukemia. Med Pediatr Oncol. 2003;40:51–53.
6. Margolin K, Traweek T. The unique association of malignant histiocytosis and a primary gonadal germ cell tumor. Med Pediatr Oncol. 1992;20:162–164.
7. Solomonov A, Zuckerman T, Goralnik L, et al.. Non-Hodgkin’s lymphoma presenting as an endobronchial tumor: report of eight cases and literature review. Am J Hematol. 2008;83:416–419.
8. Hornick JL, Jaffe ES, Fletcher CD. Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy. Am J Surg Pathol. 2004;28:1133–1144.

primary; endobronchial tumor; histiocytic sarcoma; papillary carcinoma thyroid

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