Address for correspondence : Dong Wook Lee, MD, Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Chungbuk National University, 776 1sunhwan-ro, Seowon-gu, Cheongju 28644, Korea
Tel : +82-43-269-6157, Fax : +82-43-265-6157, E-mail : dwlee@chungbuk.ac.kr

Introduction

Histiocytic sarcomas (HSs) are malignant proliferations of non-Langerhans histiocytes, excluding acute monocytic leukemia and associated neoplasms.1) The most frequently involved organs are the skin, lymph nodes, and intestinal tract.2) The presentation of HS has been reported to have a mean age of 44 years.3) Morphologically, HSs comprise a diffuse, noncohesive proliferation of large cells, with generally large, round-to-oval, irregularly folded, and eccentrically placed nuclei, similar to macrophages.1,4) Although HSs generally show focal areas of spindling (sarcomatoid areas), multifocal areas of diffuse desmin-positive spindle-to-ovoid cells, with tight storiform patterns, were noted in the present case of a 55-year-old man with a mass in the left supraclavicular area of 5 months' duration. Thus, it was difficult to exclude a rhabdomyosarcoma, leiomyosarcoma, or dendritic cell tumor. The patient was diagnosed with primary HS, with rhabdoid differentiation. To the best of knowledge, this is the first such case to be reported worldwide.

Case

A 55-year-old man visited the hospital for an evaluation of a 3 cm nontender mass in the left supraclavicular area that was increasing in size. The mass had first been detected 5 months before the visit. An examination of the area revealed a left supraclavicular multiple, mobile mass. The patient had discovered the left supraclavicular mass one week earlier. On his first visit to the hospital, fine needle aspiration (FNA) cytology was done one week after the patient had first discovered the mass. The cytology results revealed no malignant cells and no evidence of tuberculosis. We explained the result of the FNA and discussed a treatment plan with the patient. The patient decided on an observation-only approach. However the left supraclavicular mass enlarged after five month. The patient had no medical disease or symptoms, and his weight was stable. The results of laboratory tests including a complete blood count, chemical battery, and C-Reactive Protein were unremarkable. Neck computed tomography revealed an irregularly shaped mass in the left supraclavicular region, suspected to be malignant (Fig. 1). To confirm the diagnosis, left neck modified radical neck dissection (MRND) was performed. Multiple enlarged lymph node were found during the surgery.
Postoperative pathologic evaluation revealed that the tumor was composed of non-cohesive large cells, with abundant eosinophilic to amphophilic cytoplasm. The nuclei were located eccentrically, and the chromatin was coarsely clumped, with occasional visible nucleoli. The nuclei were large, and nuclear atypia was more severe than in normal histiocytes (Fig. 2A). Hemophagocytosis was occasionally observed in the neoplastic cells (Fig. 2B), and a necrotic area was also observed. Interestingly, the spindle cells exhibited rhabdoid features and grew in a tight storiform pattern, necessitating the inclusion of rhabdomyosarcoma, and leiomyosarcoma in the differential diagnosis (Fig. 2C).
To exclude metastatic carcinoma, melanoma, non-Hodgkin lymphoma, acute monocytic leukemia, Langerhans cell histiocytosis, and dendritic cell tumors, immunohistochemical study was performed. The tumor cells were positive for CD45 (Fig. 3A), CD68 (Fig. 3B), focally positive for desmin (Fig. 3C), and negative for cytokeratin, HMB-45, CD3, CD20, CD21, CD23, CD1a, S100, and myeloperoxidase. Desmin-positive cells were identical to the spindle cells that exhibited rhabdoid features and were arranged in the storiform pattern. These findings suggested their histiocytic nature, and diagnosis of HS with rhabdoid differentiation was made based on the evident rhabdoid differentiation. After MRND, chemotherapy was recommended. However, the patient refused chemotherapy, preferring alternative and complementary treatment.
The mass recurred at the same site one month later. Chemotherapy and surgical excision was recommended. Again, the patient accepted only surgical excision and refused chemotherapy. Residual mass excision wes done. The patient refused any additional treatment. After eight month, he visited emergency department due to abdominal pain. Abdomen pelvic CT show abdominal cavity metastasis. One month later, the patient died.

Discussion

HS is rare neoplasm in head and neck. Sarcoma form one percent in head and neck neoplasm. HS was founded high clinical stage at presentation. Most patients die of progressive disease. HS is aggressive with poor response to therapy. The stage of disease and possibly tumor size are considered prognostic indication. For if until now the most important prognostic factors in a case involving disseminated or central nervous system, the prognosis is not good. And if occurs as a staging area localized lesions, that the prognosis is less favourable. The size of tumor in relation to the prognosis of the disese. When mass size is bigger than 3.5 cm, prognosis is poor. In this case he has localized lesion in supraclavicle area. So, we thought would be fun prognosis. Additionaly HS is very aggressive, we chemotherapy also planned. But the patient were not implemented by stubbornly, refuse chemotherapy.
The treatment of choice for HS is wide surgical excision. If sarcoma that the local organization underwent surgical resection and radiation therapy. If sarcoma that is dissemination, chemotherapy is the principle. There is no consensus as to margin width, but 2 cm of healthy tissue is considered. Isolated radiation therapy has no role in curative management. Radiation therapy is important role as adjunctive management. Chemotherapy regimen are more controversial. Considerable regimens is doxorubicine dacarbazine and ifosamide. In recent year, stem cell transplantation, or administered thalidomide. What has been repoted to be beneficial in tracking the effects of the treatment and dissemination range of the tumor. However, in the present case, the patient refused additional treatment and evaluation.
FNA of the head and neck mass is a sensitive and specific procedure. However, FNA can result in a misdiagnois due to the sampling technique, an in adequate amount of sample material, cytological interpretation, and other limitation with the procedure. FNA is not helpful for diagnosis of HS. In patient with HSs, additional out-patient follow up and radiological evaluation are needed.
HSs are rare, poorly differentiated neoplasm with a histiocytic phenotype. Morphologically, these tumors are composed of highly-cellular non-cohesive proliferations of round, oval or polygonal cells with indistinct cellular membranes. The cytoplasm is abundant and eosinophilic to amphophilic. Nuclear atypia and pleomorphism with occasional large bizarre nuclei are the key features that distinguish HS from non-neoplastic histiocytic infiltration.
The tumor cells are positive for histiocyte-associated antigens, including CD68, and CD163, but negative for B cell, T cell myeloid, follicular dendritic cell, Langerhans cell, epithelial cell, and melanin markers. Anaplastic large cell lymphoma may be histologically indistinguishable from HS owing to the high cellularity and significant nuclear atypia with occasional large bizarre cells. However, anaplastic large cell lymphoma is negative for histiocytic markers.
The 2001 World Health Organization (WHO) classification of hematopoietic and lymphoid tissues indicated that the absence of clonal B- or T-cell receptor rearrangements is needed to establish a diagnosis of HS.5) Nevertheless, several unequivocal cases of HS with immunoglobulin heavy chain gene rearrangements have been described.6) Consequently, the current WHO classification (2008) no longer considers the absence of immunoglobulin heavy chain or T-cell receptor gene rearrangements as a criterion for HS diagnosis, although it classifies such cases as examples of transdifferentiation from one hematopoietic cell lineage to another.1) Recently, Brunner, et al.7) have provided evidence of a common neoplastic progenitor clone in a patient who had a longstanding history of follicular lymphoma, which later transformed into HS. In the case presented here, the HS had evident foci of rhabdoid differentiated, which were composed of strong desmin-positive spindle cells growing in a tight storiform pattern. Amazingly, CD68 positivity was less intense in these foci than in the background of typical histiocytic cell infiltration. These findings indicate that HS may be retro-differentiated into myeloid stem cells, become mesenchymal stem cells, and subsequently re-differentiation into myoid cells. Alternatively, HS may be directly transdifferentiated into myoid cells across the different hematopoietic and mesenchymal lineages. Unlike transdifferentiation from one hematopoietic cell lineage to another lineage, as in previously reported HS,8,9,10) the case presented here is the first to suggest the possibility of transdifferentiation from a hematopoietic cell lineage to a mesenchymal cell lineage. However, further studies are needed to explain the mechanisms involved in this transdifferentiation and the related prognostic and therapeutic considerations.

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2. So H, Kim SA, Yoon DH, Khang SK, Hwang J, Suh CH, et al. Primary histiocytic sarcoma of the central nervous system. Cancer Res Treat 2015;47(2):322-8.

3. Chan JKC. Tumors of the lymphoreticular system, including spleen and thymus. In: Fletcher CD, editor. Diagnostic histopathology of tumors. 2nd ed. London: Churchill Livingstone;2000. p.1198-9.

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7. Brunner P, Rufle A, Dirnhofer S, Lohri A, Willi N, Cathomas G, et al. Follicular lymphoma transformation into histiocytic sarcoma: indications for a common neoplastic progenitor. Leukemia 2014;28(9):1937-40.

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9. Lee SH, Park HW, Park CY, Park BC, Kim NG. Fine needle aspiration biopsy and histopathologic diagnosis in the head and neck mass. Korean J Otolaryngol-Head Neck Surg 1999;42(11):1429-34.

10. Yoo KD, Han DS, Chung SM, Kim SM, Bae JH, Eun CS, et al. [A case of extranodal histiocytic sarcoma of stomach mimicking gastric adenocarcinoma]. Korean J Gastroenterol 2010;55(2):127-32.