January 2015

A 74 year old man with a right neck level III mass

Yara Daous, M.D., Olukemi Esan, M.D. and Barbara Ducatman, M.D.

Overview

A 74 year old man, with a history of hypertension, diabetes, recent skin basal cell and squamous cell carcinomas. He presented with right sided, non-tender neck mass associated with a 30-pound weight loss over the past year. He reports no hoarsness, dysphagia, fever, or chills.

Gross Description

Fine needle aspiration of the neck mass showed large atypical cells with round, indented nuclei, vesicular chromatin, and prominent nucleoli. Scattered small lymphocytes in the background and occasional multinucleated giant cells (Fig 1 and 2).

Fig 1
Fig 2

Excisional biopsy of the neck mass showed sheets of epithelioid to spindled cells with oval, pleomorphic nuclei, vesicular chromatin, prominent nucleoli, and scant foamy to granular cytoplasm. Occasional scattered small lymphocytes and plasma cells are in the background with occasional multinucleated giant cells and mitotic activity (Fig 3, 4 and 5).

Fig 3
Fig 4
Fig 5

The tumor cells are positive for CD21, CD23, Clusterin, CD30 (Fig 6, 7 and 8), while negative for pankeratin, CK7, CK20, CK5/6, CD45, CD3, CD20, CD138, ALK, HMB-45, S100, Melan-A, and TTF-1. EBV by in-situ hybridization (EBER) was also negative.

Fig 6
Fig 7
Fig 8

Diagnosis

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Discussion

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm of unknown etiology that is morphologically and immunophenotypically similar to normal follicular dendritic cells. It is believed to arise from the antigen-presenting follicular dendritic cells of lymph node follicles, and is not considered to be of hematolymphoid in origin. It occurs primarily in young or middle aged adults with often in the fifth decade.  A minority of cases, 10-20%, arise in a background of Castleman’s disease, most commonly the hyaline vascular type.  Other associations include paraneoplastic pemphigus and schizophrenia.

FDCS usually present as a painless, slow growing lymphadenopathy predominantly involving the cervical lymph nodes but can also affect the axillary, mediastinal, mesenteric, and supraclavicular lymph nodes. Extranodal involvement has been reported in 30% of cases. These sites include the tonsils, oral cavity, gastrointestinal tract, intra-abdominal soft tissue, and breast.

Hepatic and splenic tumors can show histologic features of inflammatory pseudotumor in addition to features of follicular dendritic cell differentiation.  These tumors are not as cellular and have a prominent lymphoplasmacytic infiltrate.

Grossly, these lesions are around 5 cm. However, larger lesions up to 20 cm have been reported to arise in the retroperitoneum and mediastinum. They tend to be well circumscribed and have solid, tan-pink cut surfaces. Larger tumors may have areas of hemorrhage and necrosis.

Microscopically, they commonly assume a storiform or whorled architecture composed of spindled cells with oval nuclei. The nuclei have a vesicular or granular chromatin pattern, thin nuclear membranes, and small but distinct nucleoli. The cells have a moderate amount of eosinophilic, granular cytoplasm.  Nuclear pseudoinclusions and multinucleated giant cells may be occasionally found. Small T-lymphocytes, and rarely plasma cells, characteristically surround tumor cells and perivascular spaces (perivascular cuffing).  Mitotic rate is usually  <10 mitoses per 10 high power fields.

Some tumors may exhibit a size > 6 cm, necrosis, significant cytological atypia, and pleomorphism, and a high mitotic rate including atypical mitoses. This is mostly seen in deep-seated intra-abdominal tumors and carries a poorer prognosis.

By electron microscopy, these tumors have numerous long and thin cytoplasmic processes, cell junctions and desmosomes. No Birbeck granules are seen.

Immunohistochemical studies are important for the diagnosis. The tumors cells are positive for CD21, CD23, and CD35, which are highly specific. They are also positive for clusterin, vimentin, fascin, epidermal growth factor receptor, and HLA-DR. S100 is rarely positive. EMA may be positive in tumor cells but not normal follicular dendritic cells, unlike the previously mentioned stains which are positive in both normal and neoplastic cells. CD45, CD3, CD20, CD34, and CD1a are usually negative.  EBV-encoded RNA (EBER) is detected in most splenic and hepatic but not in nodal FDCS’s.

FDCS is considered to be a low-grade sarcoma and behaves as such rather than malignant lymphoma. The treatment of choice is complete surgical resection with or without chemotherapy and radiation. However, it tends to locally recur in 40-50% of cases. Metastasis occurs in about 25% of cases.

The differential diagnosis includes but not limited to interdigitating dendritic cell sarcoma, thymoma, spindle cell carcinoma, malignant melanoma, and sarcoma.

References

  1. Hematopathology, histiocytic and dendritic cell neoplasms by Elaine Sarkin JaffeNancy Lee HarrisJames W. VardimanElias Campo.
  2. Chan JKC. Proliferative lesions of follicular dendritic cells, an overview, including detailed account of follicular dendritic cell sarcoma, a neoplasm with many faces and uncommon etiologic associations. Adv anat Pathol 1997;4:387-411.
  3. Perez –Ordonez B, Rosai J. Follicular dendritic cell tumor:review of the entity. Semin Diagn Pathol 1998;15:144-54.
  4. Pallesen G, Myhre-Jensen O: Immunophenotypic analysis of neoplastic cells in follicular dendritic cell sarcoma. Leukemia 1:549, 1987.