INTRODUCTION
The World Health Organization (WHO) recognises histiocytic sarcoma as one of six subtypes of dendritic lineage neoplasms which also include: follicular dendritic cell sarcoma, interdigitating cell sarcoma, Langerhans cell sarcoma, Langerhans cell histiocytosis, and dendritic cell sarcoma not otherwise specified.Reference Jaffe1 Previously, this entity, along with several T- and B-cell non-Hodgkin’s lymphomas, was termed a ‘true histiocytic lymphoma’. That term is no longer used as no other member of the group met qualifications for both histiocytic and lymphomatous designation.Reference Wilson, Weiss, Gatter, Mason, Darfman and Warnke2, Reference Egeler3 Despite the new nomenclature, histiocytic sarcoma remains very difficult to diagnose due to overlapping immunohistochemistry with the other dendritic cell neoplasms.
In general, histiocytic sarcoma is a rare but aggressive tumour that often spreads to extranodal sites.Reference Gonzalez and Jaffe4 Consequently, optimal roles for chemotherapy, radiotherapy and surgery remain unknown.
The following report discusses a single case of histiocytic sarcoma in an elderly woman treated with external beam radiotherapy (EBRT) alone followed by a discussion of the relevant literature.
CLINICAL HISTORY
A 79-year-old woman was diagnosed with stage IIIa follicular-type non-Hodgkin’s Lymphoma in 2008 from a left-sided cervical lymph node biopsy. The patient was observed without active treatment.
In 2013, the patient noted a painful, enlarging mass in the left axilla along with night sweats. Pathologic examination of an excisional biopsy initially reported a granulocytic sarcoma. The lesion stained positive for CD4, CD68, CD33 and partially for CD163, all of which are common markers for both granulocytic and histiocytic sarcomas. However, a pathology review performed at the National Cancer Institute with additional immunohistochemistry testing revealed S-100 and CD1a positivity in the periphery of the lesion, and the patients bone marrow biopsy failed to support a myeloid etiology. Thus, a diagnosis of histiocytic sarcoma was favoured. A positron emission tomography scan was then performed, and the left axillary basin revealed grossly enlarged and intensely hypermetabolic lymph nodes with active diffuse inflammatory stranding involving the entire left axilla. The largest of these left axillary nodes had a photopenic center consistent with necrosis, and the most metabolically avid left axillary lymph node had a standard uptake value of 11.
The patient denied pain but noted continued growth in the biopsied area of her left axilla. On exam, diffuse 1–3 cm adenopathy was palpated in the cervical, supraclavicular and inguinal regions, and one ~8 cm mass was evident beneath a well-healed excisional biopsy incision in her left axilla. The lesion was not tender or fixed.
Radiation therapy to her biopsy-proven histiocytic sarcoma with 1·8 Gy fractions with re-evaluation after 10 treatments was planned. The gross tumour volume and dose cloud distribution can be seen in the image provided. After these initial ten treatments, the patient’s 8 cm lesion had regressed to ~5 cm in diameter so treatments were continued. After 45 Gy, the lesion had resolved and her only acute adverse effect was a mild radiation dermatitis that resolved within 4 weeks. The subsequent PET scan showed resolution of her left axillary disease. However, the scan also showed progression of her other mildly avid lymphoma lesions. Subsequent work-up showed a new diagnosis of acute myelogenous leukemia. The patient died 5 months later from disseminated leukemia.
DISCUSSION
This case not only reinforces that histiocytic sarcomas are difficult to diagnose but more importantly evidences that EBRT to 45 Gy can provide local control of this disease.
A number of cases of histiocytic sarcomas have been reported with varying approaches to therapy, including surgery with and without adjuvant EBRT, chemotherapy, and several combination and salvage treatments, yet the outcomes in the vast majority of these patients proved to be poor response or recurrence (local or distant) with little evidence suggesting a survival benefit.Reference Vos, Abbondanzo, Barekman, Andriko, Miettinen and Aguilera5, Reference Almefty, Tyree, Fusco, Coons and Nakaji6
Our finding that EBRT can provide excellent local control is supported by other reports detailed in the table provided.Reference Vos, Abbondanzo, Barekman, Andriko, Miettinen and Aguilera5–Reference Mainardi, D’Amore, Pillon, Toffolutti and Rosolen9 We reference a report by Buonocore, et al. that describes a 3-year-old child who developed a neurogenic bladder from a histiocytic sarcoma involving his fourth lumbar vertebral body. EBRT to 45 Gy in 1·8 Gy fractions was used to reduce the mass and alleviate the patient’s symptoms. A separate thoracic spine lesion and two pulmonary metastases were later treated with an additional 45 Gy with a complete response.Reference Buonocore, Valente, Nightingale, Bogart and Souid7
Adjuvant radiation therapy has also been used successfully to treat histocytic sarcoma. Hornick, et al. analysed 14 cases treated surgically of which four received adjuvant radiation therapy. Local recurrences and mortality were found in patients receiving no adjuvant therapy or adjuvant chemotherapy alone, but the three patients not lost to follow-up after adjuvant radiation (median follow-up=26 months) remained without evidence of disease.Reference Hornick, Jaffe and Fletcher8
Chemotherapy regimens have been attempted. Yoshida et al. report on a patient who presented with disseminated intravascular clotting and was found to have bone marrow invasion of large cells classified immunohistochemically as histiocytic sarcoma. Treatment with intravenous heparin and six cycles of modified cyclophosophamide, doxorubicin, vincristine, etoposide, prednisone, and filgastrum (CHOEP-14) chemotherapy, caused resolution of pancytopenia after ten days. The patient remained without evidence of disease at her 22-month follow-up.Reference Yoshida and Takeuchi10
CONCLUSIONS
Our experience at Roswell Park Cancer Institute, along with several experiences within the limited literature, speaks to the efficacy of radiation therapy in achieving local control. Diagnosis remains difficult and often controversial. Optimal systemic therapies are not yet known.
Figure 1 Gross tumour volume (GTV) contours and dose cloud distribution for 45 Gy 3D-conformal radiation treatment of a left axillary histiocytic sarcoma.
Table 1 Radiation therapy for histiocytic sarcoma
Abbreviations: RT, radiation therapy; EBRT, external beam radiation therapy; LCH, Langerhans cell histiocytosis; PBSCT, peripheral blood stem cell transplant; OS, overall survival; DOD, dead of disease; LR, local recurrence.
