Nodal follicular dendritic cell sarcoma with four atypical histomorphologic features: an unusual case report
Follicular dendritic cell sarcoma (FDCS) is a rare malignancy. In addition to the classical histopathologic features, it has also some special morphological variants that can present a challenge in the diagnosis of this disease.
A 45-year-old male who presented with a left supraclavicular mass was given a final diagnosis of FDCS after lymph node biopsy. The specimen obtained during radical resection revealed five different morphologies, including the classical histological appearance and atypical areas resembling desmoplastic infiltrative carcinoma, anaplastic large cell lymphoma (ALCL), hemangiopericytoma and classical Hodgkin’s lymphoma (CHL). Immunohistochemistry was notable for positive CD21 and CD23 expression across all morphologies. Given the atypical appearance and location, the specimen was initially misdiagnosed as a metastatic carcinoma based on histology alone at an outside institution. The patient eventually underwent surgical resection followed by adjuvant chemotherapy and radiation. Despite treatment, the disease progressed, and the patient passed away 36 months after surgery.
This unusual case of FDCS contains four types of atypical histomorphologies within a single tumor specimen, including those resembling ALCL and hemangiopericytoma which are described here for the first time. Our report further expands the histopathologic spectrum of FDCS and may help assist in the diagnosis of other such challenging cases.
KeywordsFollicular dendritic cell sarcoma Histomorphology Variants Diagnosis
Anaplastic large cell lymphoma
Anaplastic lymphoma kinase
Classical Hodgkin’s lymphoma
Epithelial membrane antigen
Follicular dendritic cell
Follicular dendritic cell sarcoma
Leukocyte common antigen
Magnetic resonance imaging
Positron emission tomography and CT
Smooth muscle actin
Follicular dendritic cell sarcoma (FDCS), an uncommon malignancy found primarily in cervical lymph nodes, is characterized by its follicular dendritic cell (FDC) differentiation . The typical morphology of FDCS includes ovoid- to spindle-shaped tumor cells arranged in fascicular, storiform or whorled patterns; these tumor cells have indistinct cellular borders with lightly eosinophilic cytoplasm, delicate nuclear membranes with granular or vesicular chromatin, and small but distinct nucleoli. In the background, small lymphocytes can often be noted throughout the tumor [2, 3]. However, when these typical morphologies are not present, the diagnosis can be more challenging. Previous studies have reported cases of FDCS that resemble poorly differentiated carcinoma [3, 4]. A biopsy can show epithelioid and pleomorphic tumor cells with marked nuclear atypia; when these round or polygonal epithelioid cell nests appear in lymph nodes, the tumor is remarkably similar to metastatic carcinoma, especially in the appropriate clinical context.
Here, we report an unusual case of FDCS in the left supraclavicular lymph node. In addition to the classical histologic features, it also exhibits four atypical morphologies: those mimicking desmoplastic infiltrative carcinoma, anaplastic large cell lymphoma (ALCL), hemangiopericytoma and classical Hodgkin’s lymphoma (CHL). These atypical histological features pose a great challenge to diagnosis. This case extends the morphologic spectrum of FDCS and furthers understanding of this rare tumor.
A 45-year-old male presented with a hard, fixed, 4 cm mass in the left supraclavicular fossa without pain, redness, swelling, or fever. Ultrasound revealed multiple enlarged lymph nodes that were not palpable by physical exam and that were subsequently biopsied. The initial diagnosis was metastatic poorly differentiated carcinoma, and evaluation for a primary tumor was recommended. The initial evaluation was performed at an outside institution; the patient was not a surgical candidate and was subsequently referred to our center for further treatment.
This case posed a variety of diagnostic challenges. One such challenge was the location of the tumor in the left supraclavicular fossa and its atypical histological appearance. In elderly patients, enlarged lymph nodes at this site are most commonly associated with metastasis, particularly of gastric cancer or lung cancer. Moreover, the morphology observed in the biopsy specimen seemed consistent with metastatic carcinoma, which resulted in the initial diagnosis. This was only doubted after no primary lesion was found on further evaluation. Pailoor J et al. reported a case of FDCS in inguinal lymph nodes, which was also initially diagnosed as metastatic carcinoma, even in the surgically resected specimen . The teaching point of this case is that although the epithelioid tumor cell nests had infiltrated into the hypertrophic collagenous stroma, the tumor cells were relatively bland with abundant cytoplasm and lacked crowded or overlapping nuclei. Furthermore, multinucleated giant cells could be readily observed. These morphologic features may be useful in distinguishing FDCS from metastatic carcinoma.
Most notably, this FDCS case demonstrates a spectrum of morphologies. The histomorphology of FDCS is usually heterogeneous and has been known to show epithelioid or pleomorphic tumor cells [5, 6, 7, 8], myxoid stroma [9, 10], osteoclastic giant cells [11, 12], and CHL-like features [6, 13], among others. However, in this case, the four atypical histopathologic morphologies were all present within the same tumor, which has not been previously reported. In addition, to the best of our knowledge, the morphological variants resembling ALCL and hemangiopericytoma are described here for the first time.
Discussion of this case will help pathologists to better understand this heterogeneous tumor and to avoid diagnostic error. The first preoperative biopsy may have involved the resection of just the lymph node containing invasive epithelioid cell nests, which resulted in the initial misdiagnosis. The areas similar to ALCL or CHL but that were CD30-positive by IHC (it has been reported that a few FDCS could express CD30 [6, 13]) are another point of diagnostic importance. The treatment of FDCS is typically surgical resection, whereas lymphoma is treated with chemotherapy and radiation. Furthermore, if the IHC results were negative for CD30, CD15, PAX-5, CD20, CD3, EMA and LCA, it would be very difficult to make a definitive diagnosis without knowledge of these FDCS variant morphologies.
No gold standard treatment has been established for FDCS. Radical surgical resection is most often the first treatment choice, and the benefits of adjuvant therapy are controversial. Current studies suggest that patients who undergo surgery alone have a better overall survival than those that receive other treatments and that postoperative adjuvant radiation has no benefit . However, Spatola C et al.  demonstrated that adjuvant therapy could strengthen the local control of the disease; Pang J et al.  also showed that surgery alone was associated with higher rates of relapse than postoperative adjuvant therapy. Considering the adverse factors [2, 13] in our case including that the maximum tumor diameter was ≥6 cm and that coagulative necrosis, cells with marked atypia, and a focally high mitotic count (> 10/10 high-power fields (HPF)) were observed, the patient received chemotherapy and radiotherapy after radical resection. The patient’s condition was initially well controlled until premature discontinuation of chemotherapy resulted in relapse; subsequent radiation did not effectively control disease progression. At least in this patient’s case, postoperative adjuvant therapy did help control disease burden but not after relapse. At this time, whether patients with recurrent tumors should undergo repeat resection requires further study.
We report an unusual case of FDCS in the left supraclavicular lymph node with four atypical histomorphologies. These morphologic variants could present a great diagnostic challenge. A better understanding of the variants and familiarity with the immunophenotype will help in the diagnosis of FDCS.
The authors thank the patient and his relatives for agreeing to our report and for providing a detailed medical history. They are also grateful to Fan Zhou, M.D., Ph.D., (Department of Pathology, Saint Agnes Medical Center, Fresno, CA 93720), for the careful revision of this manuscript. They also thank the American Journal Experts who provided the professional language editing service.
Study concepts and design: GJD, XCY, YLW. Data acquisition: YLW, FW, YZ. Data analysis and interpretation: GJD, FW, YZ. Manuscript preparation: YLW, RAM, GJD. Manuscript review: GJD, XCY, RAM. Corresponding author: GJD, XCY. All authors read and approved the final manuscript.
This work was financially supported by a grant from the Natural Science Foundation of China (No.81171848).
Ethics approval and consent to participate
This study was approved by the Ethics Committee of Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China (No. KY201818). Written informed consent was obtained from the patient for the storage of samples and data, follow-up contact, and further use of samples and data for research purposes.
Consent for publication
The authors declare that they have no competing interests.
- 8.Wu B, Lim CM, Petersson F. Primary tonsillar epithelioid follicular dendritic cell sarcoma: report of a rare case mimicking undifferentiated carcinoma and a brief review of the literature. Head Neck Pathol. 2019. https://doi.org/10.1007/s12105-019-01015-3 Epub ahead of print.
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