Introduction

Histiocytic Sarcoma (HS) is an extremely rare non-Langerhans histiocyte disorder. This disorder is characterized by the multiplication of malignant cells having characteristics of mature histiocytes [1]. The etiology of HS is unknown. HS is mainly seen in adults (mean age being 46 years); however, pediatric histiocytic sarcoma cases have been reported. It has a slight male predominance [2].

The symptoms appear most commonly due to the involvement of unifocal or multifocal extra-nodal tumors including spleen, soft tissue, lung, nasal cavity, lungs, brain, gastrointestinal tract, and skin [2,3,4]. Patients may present with hepatosplenomegaly, adenopathy and non-specific systemic symptoms like fever, weight loss, anorexia, and asthenia, which are common presentations in patients with HS [5]. In a few cases, asymptomatic involvement of the organs is incidentally discovered on imaging [6].

The pretreatment work-up for HS should include initial histologic confirmation, complete blood count, liver and renal function tests, a computerized tomography (CT) scan, and positron emission tomography (PET) imaging modalities for evaluating organ involvement and bone marrow biopsy [7].

The pathogenesis of HS is ambiguous. Being derived from cells of monocytic and macrophage systems, HS cannot be regarded as a true sarcoma. It is commonly associated with follicular lymphoma, acute myeloid leukemia, and acute lymphoblastic leukemia [8].

HS often presents with a solid tumor composed of sheets of large epithelioid cells with abundant rare mitotically active and necrosis is present. The IHC is necessary for diagnosis and shows positivity in CD68 and CD163. The literature is suggestive of positivity for at least two of CD68, CD163, CD4, and lysozymes for diagnosis [9, 10].

The diagnosis of HS is based on the anatomo-pathological evaluation of the involved tissue along with clinical correlation. It is important to note immunohistochemistry (IHC) is used to establish the diagnosis. It is important to note that less than 20% of HS cases show solitary involvement of a lymph node. Diagnosis is challenging, because these tumors are rare and consideration must be given to other differential diagnoses, including histiocytic and dendritic cell disorders, metastatic solid or hematopoietic neoplasms, primary familial lymphohistiocytic disorders, sarcomas, carcinomas, and acquired causes of hemophagocytic macrophage activation syndromes [10].

Given the rarity of this tumor and no known treatment protocol, accurate diagnosis is crucial for treatment planning. We are presenting a diagnostically challenging case to emphasize the clinicopathologic features of these rare tumors and to raise awareness among our pathologist colleagues.

Case presentation

We report a case of a solitary HS arising from an inguinal lymph node in a 53-year-old asymptomatic woman who presented with a groin mass and no known previous history of hematologic disease. Radiology revealed a 2.7-cm right inguinal mass without intra-pelvic, intra-abdominal, or thoracic lymphadenopathy. All the base line laboratory work-up, including complete blood count, comprehensive metabolic panel, and urine analysis were within normal limits. The fine-needle aspiration (FNA) biopsy revealed pleomorphic and high-grade cells with spindle cell morphology in the background of mixed inflammation. Those cells were weakly positive with smooth muscle actin (SMA) which raises the diagnosis of a high-grade sarcoma, such as leiomyosarcoma or a myofibroblastic tumor.

Considering the rarity of intra-nodal HS, HS was not the most suspected differential diagnosis and the surgical team resected the tumor. The subsequent resection demonstrated a nodule consistent with a lymph node involving extensive replacement by a neoplasm with focal riming of lymphoid tissue at the periphery and a small, centrally located stellate necrotic focus. The tumor invaded through the capsule into the surrounding adipose tissue.

The tumor shows an epithelioid to spindle cell morphology with large uniform nuclei and prominent nucleoli. Mitoses were easily seen with up to 28 mitotic figures per 10 high power field. IHC stains were strongly and diffusely positive for CD68, CD163, Vimentin, weakly positive SMA and CD45 and negative for Pan-Cytokeratin, Sox10, S100, MitF, CD15, CD30, Pax5, CD3, CD20, ALK protein, Cytokeratin 5/6, CD56, CD1a, CD21, CD23, and Clusterin (Fig. 1).

Fig. 1
figure 1

a Hematoxylin and Eosin (H and E), 4 × 10, lymph node with a nodular infiltrate, and focal riming of lymphoid tissue at the periphery. b H and E, 20 × 10, tumor cells show an admixed of epithelioid to spindle cell morphology with large uniform nuclei and prominent nucleoli. c H and E, 40 × 10, frequent mitoses are easily seen with up to 28 mitotic figures per 10 high power field. d CD68 IHC, 40 × 10, diffuse and strong expression. e FNA, Diff-Quick stain, 20 × 10, highly pleomorphic cells in background of inflammatory cells. f FNA, Papanicolaou stain, 40 × 10, a large malignant cell with high-grade atypia and irregular border

Full size image

No follow up could be conducted, because the patient never returned to our facility after the re-excision surgery.

Discussion

Histiocytic sarcoma commonly presents as a solitary mass at an extra-nodal site [11]. This case presented with a mass originating from an inguinal lymph node without any extra-nodular involvement.

HS prognosis is poor and correlates with the staging of the disease and tumor size [1]. Interventions such as surgery, radiotherapy, chemotherapy, and their combinations are often required for the management of the disease and should be determined on a case-by-case basis [2, 12].

The role of the anatomo-pathological test of the afflicted organ or tissue in giving a definite diagnosis in case of histiocytic sarcoma is undisputed. Complete or incomplete effacement of the lymph nodes is common when they are affected by histiocytic proliferation of the malignant cells. There is much variability in the degree of cellular pleomorphism and mitotic activity. Abundant eosinophilic cytoplasm with vacuolated or foamy appearance is seen in most malignant cells. A noticeable single irregular nucleolus and oval nucleus containing vesicular chromatin that is eccentrically located is commonly seen in these malignant cells. Multiple nucleoli in multinucleated cells may also be found. Due to such variability, immunophenotyping and molecular studies are significant in diagnosing HS [10, 13].

In this case, the tumor shows an epithelioid and spindle cell morphology with a large uniform nucleus and a prominent nucleolus. Even though focal areas of spindled cells can be seen in HS, extensive spindling is rare. The lack of monster cells, abundant vacuolated cytoplasm, and a neutrophilic rich background, which are frequently seen in HS, diverts the attention from HS diagnosis on FNA. However, some other non-specific features of the tumor cells in our patient, such as a high mitotic index and necrosis, are frequently reported in HS [10]. One of the most challenging and unique features in this case is the positive SMA expression which is not one of the positive HS immunohistochemical markers and raises the unclassified pleomorphic sarcomas, leiomyosarcoma, and myofibroblastic tumors in the differential diagnosis. In cases like this, the diagnosis is made with confirmation of histiocytic lineage through immunophenotyping by positive expression of CD68, lysozyme, and CD163. In addition, there is a negative expression of CD1a, CD21, and CD35 [14]. In this case, IHC stains were strongly and diffusely positive for CD68 and CD163, Vimentin; weakly positive for SMA and CD45; and negative for Pan-Cytokeratin, Sox10, S100, MitF, CD15, CD30, Pax5, CD3, CD20, ALK protein, cytokeratin 5/6, CD56, CD1a, CD21, CD23, and Clusterin.

The differential diagnosis of HS is broad and may be impacted by the location and morphology of the cells. Histiocytic diseases such as Langerhans cell histiocytosis may be misdiagnosed as HS. The HS cells can also mimic lymphomas, especially in cases of intra-nodal involvement or CD3/CD4 expression. However, the lack of most B- and T-cell markers can be used to exclude lymphomas. HS arising from soft tissue may be mistaken for sarcomas. The spindle shape morphology which is seen in some subsets and high-grade features can be seen in both HS and sarcomas. In the presented case, even though HS is not arising from the soft tissue, the spindle morphology and weak SMA positivity can be suggestive of sarcoma such as leiomyosarcoma. However, the SMA expression is not strong enough for an unequivocal diagnosis and the additional IHC on the resected specimen ruled out the sarcoma differential diagnosis. When HE is involving the skin, melanoma, juvenile xanthogranuloma, or desmoplastic squamous cell carcinoma can be considered in the differential diagnosis [11, 15]. Langerhans cell histiocytosis, Langerhans cell sarcoma, and melanoma have S100 expression. In a subset of HS, S100 can be expressed which complicates the diagnosis [16, 17]. Poorly differentiated carcinoma also can overlap with HS [2, 9]. All of the mentioned differential diagnoses are excluded based on the IHC and diagnosis HS by cytomorphology alone is extremely challenging. When epithelioid large cells with multinucleation and lymphoid background are not present, HS diagnosis would be heavily dependent on the IHC and exclusion of the other possible differential diagnoses [15]. Even though FNA is used for patients with extra-nodal HS, the limitation of diagnostic material and need for extensive IHC and molecular testing makes FNA more useful in assessing the disease recurrence rather than a primary diagnosis tool.

Conclusions

The diagnosis of HS in the lymph nodes, especially as a solitary node/mass, is challenging due to its rarity and the broad range of differential diagnoses. This case demonstrates a rare presentation of HS in a 2.7-cm right inguinal mass arising from a lymph node which was almost entirely replaced the lymphoid tissue. In FNA and when the biopsy is limited, the representative cells may show an unusual histology. In such cases, IHC is the only diagnostic tool. However, to apply the correct IHC, such a rare entity such as HS should be considered in the differential diagnosis. The information presented will add to the growing body of HS literature to better inform early diagnosis and establish presentation characteristics associated with solitary involvement of a lymph node.