COVID19 induced immunosuppression and aggressive progression of primary cranial vault lymphoma presented as a management challenge, a case report, and a review of the literature.

doi:10.21203/rs.3.rs-1587934/v1

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Case Report

COVID19 induced immunosuppression and aggressive progression of primary cranial vault lymphoma presented as a management challenge, a case report, and a review of the literature.

https://doi.org/10.21203/rs.3.rs-1587934/v1

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Primary Large cell Non-Hodgkin's Lymphoma of the cranial vault is rare and association with COVID19 needs to be studied as in our patient.Our patient, a 53-year-old male noticed fast growth of posterior cranial vault tumour from 2cm to 10 cm size in last 6months after COVID 19 affliction. MRI brain with contrast revealed lesions mimicking multicentric meningioma. The whole-body PET scan was normal. Following Subtotal excision of the mass, histopathology revealed large B-cell Non-Hodgkin's lymphoma (DLBCL). Immunohistochemistry showed positive for CD10, CD20, CD45 (LCA), ALK, and BCL-VE with Ki-67 index 90–95%. Following radiotherapy and chemotherapy patient is disease-free on imaging and doing well at 5 months of follow-up.Early intervention with excisional biopsy and timely chemo and radiotherapy in presence of favourable immunostaining may add survival benefit even in the presence of malignant features induced by immunosuppressing disease as COVID19.Although this association was noticed in this single case study but role of Covid 19 infection in inducing the fast progression of tumours which can be expedited in immunosuppressive condition cannot be ignored.

Neurobiology of Disease

Non-Hodgkin’s large cell Lymphoma

cranial vault

COVID19

mimicking meningioma Case Presentation

Primary cranial vault lymphoma is rare and not more than 50 case reports are reported. Once these lesions convert to high-grade, they may present as an osteolytic lesion, uncommonly as osteoblastic lesion and with permeative transmission through cortex rarely^.[1] Among these cases, concomitant calvaria and the epidural lesions are few and far between (5-6) the reported patients with Nonhodgkin’s large B cell lymphoma^.[2,3] Its association with the immunosuppressive condition is well known but its association with Covid 19 had not been reported. In such a scenario progression of the lesion, clinical behaviour, management strategies, and prognosis need to be redefined.

A 53 years male patient, presented with huge scalp mass on the right side of the scalp which was noticed by the patient as a single lesion of grape size (2.5cm) 5 years back on the posterior cranial vault but in due course of the last 6 month there was a progressive enlargement in size with three new smaller lesions on calvarias. The patient had an earlier history of COVID 19 positive twice in the last 6 months on the RT-PCR test with history of taking immunosuppressant drugs. On general examination, there were no other lymph nodes or organomegaly.. On local examination, there were firms too hard with irregular surface nodular huge scalp mass measuring about 8-10 cm in the right parietal scalp and frontal area in mideline, which was painless and non-pulsating. The skin over the swelling was normal, patchy loss of hair, no tenderness, no transparency or translucency. . Neurological examination revealed no abnormalities, and the serological tests for human immunodeficiency virus, Epstein-Barr virus, and human T-cell lymphotropic virus were negative before surgery as well he was diagnosed COVID negative on 19 RT-PCR test.

Non contrast computedtomographic (NCCT) examination done 6 month back for right parietal swelling showed (soft tissue Iso to hyper dense tumour in the right frontoparietal region with the exclusion of the invasion of the skull (Figures1a). There was no concurrent nodal or intracranial (extradural/meningeal) involvement or invasion of the orbit 6 months back. Magnetic resonance imaging was done 6 months after CT demonstrated a multiple-nodular huge scalp mass with heterogeneous signals with isointense on T1 weighted imaging and heterogeneous signals on T2-weighted imaging(Figure 1b,1c). On T2 weighted images, there were hypointense changes in cortical bone and it was having patchy contrast enhancement suggesting tumourinfiltration (Figure 1b). There were lesions in the anterior frontal region appearing to be epidural and compressing anterior sagittal sinus and a small epidural deposit on the left parietal region (Figure1c). On Contrast scan lesion was homogenously contrast-enhancing with Dural tail positive (Figure 1d) and Magnetic resonance arteriography angiography revealed tumourbeing supplied by bilateral ECA (Figure 2a) with tumor blush present on digital subtraction angiography on ECA injection (Figure 2b). Findings were suggestive of caldaria atypical meningioma’s.DSA also revealed non-visualization of the anterior sagittal sinus and left transverse sinus (Figure 2c). PET scan whole body failed to identify any other evidence of primary lesion or systemic lymphoma/malignancy.

The patient was treated with gross total excision of the large rt parietal calvaria mass with excision of lesion and curettage of the underlying bone. A straight incision was made at the base of the tumor on the parietal part. Gross total resection of the tumor was performed without excising small Dural deposits in the anterior frontal and left parietal region. The tumor was seen infiltrating galea, frontalis, and occipitalis muscles. It was firm to a hard consistency, vascular, and greyish-yellow. Microscopic examination of the tissue showed discohesive malignant cells arranged in sheets infiltrated by neutrophils and lymphocytes. Cells were large with marked pleomorphism, a high N: C ratio with prominent nucleoli, and scant cytoplasm. There were extensive areas of necrosis with frequent atypical mitotic figures. The pathological diagnosis was diffuse large B-cell NHL (Fig.3a). Immunohistochemistry showed positive for CD10, CD20, CD45 (LCA), ALK with Ki-67 index 90-95 %.( Figure 3b, 3c) It is followed by cycles of chemotherapy with injection cyclophosphamide, doxorubicin, vincristine, and tab. prednisolone. (CHOP regimen) and showed a good response. Local adjuvant External beam Radiotherapy of 8 weeks, was given to the right scalp region together with chemotherapy(CHOP regimen). The patient has no residual lesion on repeat MRI at 5 months follow up and doing well. (Figure 2d)

Non- Hodgkin’s lymphoma of the cranial cavity may be present due to metastatic deposit of systemic lymphoma in 1-3 % cases and cranial vault alone rarely, but primary NHL of the cranial vault is rare. ^[1,2]Not more than 50 cases have been reported to date. Primary cranial vault lymphoma had been defined as localized lymphoma not involving other than the primary site for more than 6 months once the initial diagnosis is made.^[3]In primary calvaria lymphoma, the most common histopathology reported is NHL large B-cell type (39-78%) and in primary Dural lymphoma most common pathology reported is marginal B cell lymphoma which is low grade.

In the meta-analysis by El Asri et al., average age at presentation was 60 years without any genderprevalence. The average duration of the onset of symptoms was 6 month. ^[4] In the present case report, the patient noticed swelling5 years back on the right parieto-occipital region which was of the size of grapes (nearly 2.5cm) but he was inflicted with COVID twice within 1 year at an interval of 6 months and there was a fast progression of size and patient noticed another 3lesions on the scalp. This fast progression, in this case, maybe attributed to immunosuppression caused by COVID 19 treatment as well as the immunosuppressive therapy he had received during his treatment as he developed a drastic fall in oxygen saturation of 80% in both the episode of COVID 19 infection. IN the study by El Asri et al and Ferreri et al immunosuppressed condition had been reported in nearly 11% of patients. ^[4,5]

In the present study tumor characteristics on T1 and T2 weighted MRI were almost similar to the other reported patients with similar histopathology and ithomogenously contrasted enhancing with Dural tail sign. We noticed selective permeation of tumor mass through the cranial vault with tumor deposit on the inner table of calvaria and seeding of the dura in the anterior frontal region causing mass effect and no visualization of the anterior sagittalsinus. On DSA tumor was being fed from bilateral ECA with tumor blush present suggesting vascular lesion and anterior sagittal sinus and left transverse sinus was also not visualized. Angiographic findings were more in favour of meningioma as lymphomas are not reported to have vascular blush on angiography. Lymphoma mimicking meningioma is very uncommon and 3-4 case reports are available in the literature. ^[3,6]

In our patient MRIfindings did not reveal any widening of diploic space, there were slightly cortical changes and patchy contrast enhancement suggestive of permeation of calvaria cortex by malignant lymphomatous cells. Anteriorsagittal sinus was not visualized probably due to overlying compression by tumor mass as well metastatic deposit through emissary's veins. As the lesion was high-grade permeation of left transverse sinus through emissary veinous channel leading to thrombosis may be the reason. Such selective permeation of malignant lymphomatous cells was reported in the study byOchiai et al and Galarza et al. ^[7,8] In the study by Kissling et al the lymphomatous mass resembling meningioma have diffuse osteolytic features with thrombosis of the posterior third sagittal sinus.^[3]Such atypical radiological findings probably have not been reported which we felt need mentioning.

Faster progression of the tumor was reflected by high KI-67 proliferation index but one good prognosticfeature was the absence of BCL-2 staining which helps in good chemotherapy and radiotherapy response as reported in different studies.^[9]In the previous, reported cases mimicking meningioma BCL-2 staining in FISH were presented suggesting a poor response to treatment. ^[3,8]In these reports long follow-up is not reported. In the study by Ciarpaglini et al high-grade lesions have survival extending from 10-17 months and in low grade lymphoma 5 year survival is around 40-50%. ^[10] Our patient although have developed a multicentric tumor in due course of time, lesstumour bulk and favourable histopathology for chemo & radiotherapy had given the advantage of better survival and he is presently asymptomatic after treatment on 5 months of follow up and no fresh lesion on repeat MRI.

Patients having cranial vault primary having benign course may convert into aggressive lesion following infliction with the immunosuppressed state as in present patient study and it may present as a diagnostic dilemma but early excisional diagnosis together with favourable immunostaining with BCL-2 may add survival benefits. We thought to report this case due to unusual association with COVID 19 as well atypical presentation which was not reported in the earlier reported case which put us as in diagnostic and management dilemma.

Cranial vault primary lymphoma may have slow progression but it may acquire aggressive features induced by immunosuppressing infection as COVID19and immunosuppressant medication and present a challenge in diagnosing as well management. Early intervention with excisional biopsy and timely chemo and radiotherapy in presence of favourable immunostaining may add survival benefit even in the presence of malignant features.Although this association was noticed in this single case study but role of Covid 19 infection in inducing the fast progression of tumours which can be expedited in immunosuppressive condition cannot be ignored.

DISCLOSURES

Declaration of patient consent — Patient’s written consent for publication had been obtained. Ethical declaration – ethical clearance was waived off for case report in our institute. Financial support – Authors declare that they have not received any financial support for this article.

Conflict(s) of interest – Authors declare that there is no conflict of interest.

Salunke P, Garg R, Bal A, Kedia S, Bindal S. Primary malignant non-Hodgkin's lymphoma of the skull vault in an immunocompetent patient. Neurol India 2013;61:201–4
El Asri AC, Akhaddar A, Baallal H, Boulahroud O, Mandour C, Chahdi H, Mikdame M, Gazzaz M, El Mostarchid B, Boucetta M. Primary lymphoma of the cranial vault: case report and a systematic review of the literature. ActaNeurochir (Wien). 2012 Feb;154(2):257–65
Kissling JW, Whitney E, Cathel A, Khan YR, Mahato D. Primary Cranial Vault Non-Hodgkin's Lymphoma Mimicking Meningioma With Positive Angiography. Cureus. 2020;12(6):e8856. Published 2020 Jun 27. doi:10.7759/cureus.8856.
Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: The next step. J Clin Oncol. 2000;18:3144–3150.
Ferreri AJ, Abrey LE, Blay JY, Borisch B, Hochman J, Neuwelt EA, Yahalom J, Zucca E, Cavalli F, Armitage J, Batchelor T. Summary statement on primary central nervous system lymphomas from the Eighth international conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002. J Clin Oncol. 2003;21:2407–2414. DOI: 10.1200/JCO.2003.01.135.
Jamjoom AB, Jamjoom ZA, Naim-Ur-Rahman, Cheema MA: Primary midline cranial vault lymphoma simulating a parasagittal meningioma: the role of angiography in preoperativediagnosis. Neurosurg Rev 21:202–205, 1998.
Ochiai H, Kawano H, Miyaoka R, Kawano N, Shimao Y, Kawasaki K. Primary diffuse large B-cell lymphomas of the temporoparietal dura mater and scalp without intervening skull bone invasion. Neurol Med Chir (Tokyo). 2010;50(7):595-8. DOI: 10.2176/nmc.50.595. PMID: 20671390.
Galarza, M., Gazzeri, R., Elfeky, H. A., & Johnson, R. R., II. (2006). Primary diffuse large B-cell lymphoma of the dura mater and cranial vault, Neurosurgical Focus FOC, 21(5), 1–4.
Mahmoud HM, El-Sakhawy YN. Significance of Bcl-2 and Bcl-6 immunostaining in B-Non Hodgkin's lymphoma. Hematol Rep. 2011;3(3):e26. doi:10.4081/hr.2011.e26
CiarpagliniR, Otten P. Primary cranial vault lymphoma with brain infiltration: Case report and review of the literature. Br J Neurosurg 2012;26:756–8.

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COVID19 induced immunosuppression and aggressive progression of primary cranial vault lymphoma presented as a management challenge, a case report, and a review of the literature.

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