
==== Front
Int J Surg Case Rep
Int J Surg Case Rep
International Journal of Surgery Case Reports
2210-2612
Elsevier

S2210-2612(24)01079-4
10.1016/j.ijscr.2024.110298
110298
Case Report
Primary extranodal diffuse large b-cell lymphoma of the calf muscle mimicking a carcinoma: A rare case report
Ankita
Ahuja Sana
Malik Shaivy
Zaheer Sufian sufianzaheer@gmail.com
⁎
Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
⁎ Corresponding author. sufianzaheer@gmail.com
15 9 2024
10 2024
15 9 2024
123 1102989 8 2024
7 9 2024
13 9 2024
© 2024 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Limited.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction and importance

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma (NHL), known for its aggressive nature and tendency for extranodal extension. Extranodal involvement occurs in up to 40 % of cases, with primary lymphoma in soft tissue, particularly skeletal muscle, being exceedingly rare. This report presents a rare case of primary extranodal DLBCL in the calf muscle.

Case presentation

A 35-year-old man presented with an ulceroproliferative growth in left calf muscle, initially diagnosed as squamous cell carcinoma (SCC). Imaging studies, including CECT and MRI, were inconclusive, prompting a histological examination. Biopsy revealed large malignant cells with high mitotic activity, positive for LCA, CD20, BCL-2, MUM1, and CD10, confirming a diagnosis of primary extranodal DLBCL. The patient underwent resection followed by six cycles of chemotherapy (R-CHOP) and field radiation therapy. A follow-up PET showed significant improvement, with no evidence of disease recurrence.

Clinical discussion

DLBCL often presents with rapidly growing tumors in lymph nodes or extranodal sites. Primary skeletal muscle lymphoma, particularly of the DLBCL subtype, is extremely rare, constituting about 0.5 % of extranodal lymphomas. Diagnosis typically involves imaging and biopsy, with immunohistochemistry (IHC) being crucial for accurate classification and treatment planning.

Conclusion

DLBCL, while common among NHLs, rarely presents as primary extranodal lymphoma in skeletal muscle. The presented case underscores the importance of considering DLBCL in differential diagnoses for atypical soft tissue masses and the effectiveness of R-CHOP chemotherapy in managing this rare presentation. Prompt and appropriate treatment, such as R-CHOP chemotherapy, is essential for favorable outcomes.

Highlights

• Rare Presentation: Of primary extranodal diffuse large B-cell lymphoma (DLBCL) presenting as an ulceroproliferative growth in the calf muscle.

• Diagnostic Challenge: Initial clinical and imaging assessments suggested SCC, emphasizing the importance of biopsy and IHC for accurate diagnosis.

• Effective Treatment: The patient responded well to the R-CHOP chemotherapy regimen.

Keywords

Diffuse large B-cell lymphoma
Extranodal
Ulceroproliferative
Skeletal muscle
==== Body
pmc1 Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most frequently diagnosed among the various types of non-Hodgkin's lymphoma (NHL). It is associated with aggressive behavior and a tendency for extranodal extension. Extranodal sites include the testis, skin, lung, bone and central nervous system, and the respiratory and gastrointestinal tracts [1]. Primary skeletal muscle lymphoma is an extremely rare type of DLBCL, especially in the thigh and calf regions. The primary symptoms usually include pain and swelling. The mechanisms explaining the soft tissue involvement by lymphoma include direct invasion from adjacent lymph nodes, metastatic spread, and, least commonly, primary muscle lymphoma [3]. The subcategorization of lymphoma is primarily based on immunohistochemistry used and also helps in making decisions on treatment. We present a rare case of DLBCL involving the calf muscle, which presented with an ulceroproliferative growth, following the SCARE guidelines [4].

2 Case report

A 35 year-old-male presented with a non-healing wound over left calf since last 6 months, along with that he had an enlarged inguinal lymph node on the same side for 1 month. The patient was apparently doing well 7 months back. The swelling eventually progressed to an ulceroproliferative growth. Physical examination revealed an ulcer in the left calf, measuring 8 × 8 cm which bled on touch. However, it was not associated with any local rise in temperature. The inguinal lymph node measured 6 × 6 cm. A clinical diagnosis of squamous cell carcinoma (SCC) was made, given that long-standing non-healing ulcer was present. Magnetic resonance imaging (MRI) of the left calf with PD (proton density)/ (short tau inversion recovery) STIR technique showed a well-defined hyperintense lobulated mass lesion measuring 69 × 68 mm in the subcutaneous plane of the posterior aspect of the mid leg region. [Fig. 1] The lesion was extending to the overlying muscular plane. No evidence of any extension to the adjacent bone was seen. Multiple thin internal septations were seen within the mass lesion. Histopathological correlation was advised. No other lesions were identified on MRI.Fig. 1 Radiological and clinical image. a) The clinical image showed an ulceroproliferative growth over the left calf measuring 8 × 8 cm. b) Magnetic resonance imaging (MRI) of the left calf showed evidence of a well-defined PD/STIR hyperintense lobulated mass lesion of size measuring 69 × 68 mm in the subcutaneous plane in the mid-leg.

Fig. 1

CECT revealed a large well defined lobulated heterogeneously enhancing mass lesion with left inguino-femoral region showing focal infiltration into underlying anterior and medial compartment muscles which appeared diffusely bulky with subcutaneous stranding and encasement of left femoral vessels. Histopathological correlation was advised to rule out malignancy. No other lesions were noted on the whole body CECT.

An incisional biopsy was taken which exhibited infiltrates of large malignant cells arranged in diffuse sheets with round to oval vesicular nuclei, prominent nucleoli and moderate to abundant cytoplasm. In addition, high mitotic activity was noted. Immunohistochemistry demonstrated positive staining for LCA, CD20, BCL-2, MUM1, and CD10 and negative staining for panCK, vimentin, Melan-A, HMB-45 and CD30 (to exclude carcinoma, sarcoma, melanoma and anaplastic large cell lymphoma respectively). Ki-67 labelling indexwas 65-70 %. [Fig. 2, Fig. 3] Thus, a final diagnosis of primary extranodal DLBCL- germinal centre type arising from the calf muscle was made. The exophytic mass was excised and subsequently, the patient was started on a chemotherapy regimen with doxorubicin (50 mg/m2), rituximab (375 mg/m2), vincristine (1.4 mg/m2), and cyclophosphamide (750 mg/m2), administered intravenously for six cycles. This was followed by three additional cycles of rituximab every three months. Further, the patient was given field radiation therapy of 30 Gy.Fig. 2 Histopathological images. a, b) H&E image exhibited effacement of nodal architecture with sheets of large malignant cells having round to oval vesicular nuclei with moderate to abundant cytoplasm [×10, ×40].

Fig. 2

Fig. 3 Immunohistochemical panel. a-d) IHC images of tumor cells show positive expression for CD20 (a), CD10 (b), Bcl2 (c) with a Ki67 proliferation index of 70 %. [×20].

Fig. 3

A follow-up PET scan one month after treatment showed significantly decreased activity in the left lower extremity. Currently, patient is under follow-up with no evidence of any disease recurrence.

3 Discussion

DLBCL is the most common type of NHL, accounting for about 30–40 % of cases. It primarily affects older adults, with the median age at diagnosis being around 60–70 years. The incidence rate increases with age, and it is more frequently diagnosed in men than women. Due to its aggressive nature, DLBCL often presents with rapidly growing tumors in lymph nodes or extranodal sites and requires prompt and intensive treatment [5].

Primary malignant lymphomas of soft tissues are uncommon and NHL in primary skeletal muscle (PSM) is even rarer [5]. PSM diffuse large B-cell type, was initially described by Kandel et al. in 1984 [6]. It constitutes about 0.5 % of extranodal lymphomas, with an incidence rate of less than 0.1 % among all lymphomas affecting the extremities [7]. Primary skeletal muscle NHL of diffuse large B-cell type can manifest in one of three ways: as a disseminated disease through hematogenous or lymphatic pathways; by extending from nearby organs like bones or lymph nodes; or, in very rare cases, as primary extranodal disease [8]. Table 1 summarises the findings of previously reported cases of primary skeletal muscle NHL in literature.Table 1 Previously reported cases of primary soft tissue lymphoma in literature to date.

Table 1S.no	Author	Reported cases	Age	Gender	MRI	Involved site	Histopathological diagnosis	IHC	
1.	Binici et al [3]	1	41 years	F	Lesion was isointense to muscle on T1-weighted images (WI) and hyperintense on T2-WI.	Right lower limb	DLBCL	CD20 and CD79a positive along with Ki67–50 %	
2.	Duan et al [13]	13	7–79 years (46.2 years)	M:F = 11:2	–	8-Lower extremities,
4-Trunk,
1-Upper extremity
	9- High grade B cell lymphoma,4- T cell lymphoma.		
3.	Zhang et al [14]	1	76 years	F	Bulky uniform distension of skeletal muscles, which was hyperintense relative to normal muscle	Right thigh and calf muscle	DLBCL	CD20 and CD79a positive along with Ki67–70 %	
4.	Muralidharet al [15]	1	68 years	M	–	Left lumbar region	DLBCL	LCA, CD20, BCL2 and MUM1 positive and Ki67–70 %	

DLBCL typically presents as a rapidly growing lymph node or mass, often accompanied by “B” symptoms such as fever, weight loss, and night sweats. Extranodal involvement most frequently affects the gastrointestinal tract or bone marrow [1]. Infrequently, DLBCL may affect skeletal muscle, characterized by muscle swelling, limb pain, and edema, typically without signs of heat or redness. Furthermore, it can present as isolated lesions [9,10]. The present case manifested as an ulceroproliferative growth mimicking a SCC on clinical examination.

In terms of clinical presentation, genetic findings, response to medication, and prognosis, it is varied. DLBCL NOS is classified into the activated B cell (ABC) subtype and the germinal center B cell (GCB) subtype based on gene expression profiling. Roughly 10–15 % of cases cannot be classified. The prognosis of patients with the GCB subtype is typically better than that of patients with the ABC subtype. Only 5 % of the 40 % of cases that present as extranodal lesions have been reported to involve soft tissue. [2,15].

A mass lesion may appear on CT or MRI scans, but confirming the diagnosis requires a biopsy [11]. According to Lim et al., MRI is the most valuable imaging technique for assessing muscular lymphoma [12]. Lee et al. advised performing routine plain radiography and MRI in patients with a soft tissue mass before proceeding to biopsy [2]. This condition commonly affects skeletal muscles in the lower extremities, pelvis, and gluteal regions.

The infiltration of lymphoma into the skeletal muscle can mimic melanoma, osteosarcoma, metastatic carcinoma, and sarcoma, making diagnosis more difficult [15]. Due to its overlapping morphological features, IHC is needed to confirm the diagnosis.

Curative or palliative immunochemotherapy is the mainstay of treatment for DLBCL. R-CHOP is the recommended course of treatment; in more difficult instances, adjustments may be necessary [14]. Previous literature has revealed that a positive expression of Bcl2 is linked to a poor prognosis, regardless of MYC expression and the international prognostic index [15,16].

4 Conclusion

DLBCL is a prevalent subtype of NHL primarily affecting older adults, characterized by aggressive growth and frequent extranodal manifestations. While DLBCL commonly involves lymph nodes and organs like the gastrointestinal tract, its occurrence in skeletal muscle is extremly rare. The presentation in the form of an ulceroproliferative growth is an even rarer occurrence. Diagnosis often involves imaging modalities like MRI and requires histopathological confirmation through biopsy. Treatment typically involves immunochemotherapy, with R-CHOP being the standard regimen, though tailored approaches may be necessary in complex cases. Prognosis can be influenced by biomarkers such as BCL2 expression, highlighting the importance of personalized therapeutic strategies in managing this challenging disease.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor- in -Chief of this journal on request.

Ethical approval

This case study was conducted in accordance with the Declaration of Helsinki.

Funding

This research received no funding.

Author contribution

Conceptualization (SA, AA, SZ) Methodology (SA, SZ) Investigation (AA, SZ) Supervision (SZ) Validation (SA, SZ) Writing original draft (AA) Writing review & editing (SA, SZ).

Guarantor

Sufian Zaheer.

Research registration number

NA.

Declaration of competing interest

All authors declare that there is no conflict of interest regarding the publication of this report.

Data availability

Supporting data will be available upon reasonable request.

Acknowledgments

Not applicable.
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