Non-dermatologic isolated intracranial necrobiotic xanthogranuloma

Abstract

Necrobiotic xanthogranuloma is a condition that was first identified in 1980 based on its characteristic histological identity, and it has been known since then as a dermatologic manifestation of an underlying systemic dysproteinemia. Intracranial manifestation is a rare presentation of this condition and has been reported only once in its more than 40 years of existence. Herein and to our knowledge, we report the second observation of an intracranial manifestation and, surprisingly, the first case without the expected dermatologic and systemic dysproteinemia associations. This case identifies an existing knowledge gap in our understanding of necrobiotic xanthogranuloma and emphasises the need for further research into understanding the presentation, comorbidities and management of this condition.

Background

Necrobiotic xanthogranuloma was first identified in 1980 when it was characterised as a dermatologic disorder secondary to an underlying systemic dysproteinemia (such as multiple myeloma, cryoglobulinemia and leucopenia) or a lymphoproliferative disorder.¹ The characteristic dermatologic presentation is described as skin nodules with violaceous atrophic papules or plaques with a periorbital skin predilection and a tendency to ulcerate.^{1 2} Histologically, this lesion is described as containing granulomas with lymphoplasmacytic infiltrates and zones of necrobiosis, occasionally including cholesterol clefts, giant cells or both.² In 2020, guided by a comprehensive review of all 235 known cases of necrobiotic xanthogranuloma at that time, a team of board-certified dermatologists proposed diagnostic criteria.² The proposal requires the presence of both clinical and histological features of necrobiotic xanthogranuloma and either a systemic comorbidity (paraproteinemia, lymphoproliferative disorder or plasma cell dyscrasia) or periorbital skin lesions.² Medical management therapies with intravenous immunoglobulins (IVIG), corticosteroids or combination therapy including corticosteroids are reportedly most efficient in treating necrobiotic xanthogranuloma.³

Intracranial manifestation is rare and has been reported only in 1 of the 235 known cases (0.4%).^{2 4} Fulfilling the proposed diagnostic criteria in addition to histological verification of the intracranial lesion, that patient had the characteristic cutaneous lesions with periorbital concentration for 5 years prior to the intracranial lesion diagnosis. However, he lacked the expected underlying paraproteinemia, malignancy, plasma-cell dyscrasias and lymphoproliferative disorders.⁴ Here, we report a second case of a histologically verified intracranial necrobiotic xanthogranuloma but the first to lack both associated cutaneous lesions and underlying systemic comorbidities.

Case presentation

A man (age in his mid-40s) presented for neurosurgical evaluation on referral from his ophthalmologist with a primary complaint of left-sided proptosis that became prominent during the previous 2 years but progressed most rapidly within the last 6 months. A concurrent rapid decline in visual acuity during this 6-month period was particularly concerning. On physical examination, a large, palpable, fluid-filled supraorbital mass was appreciated.

Investigations

CT of the orbit revealed a 3.2 cm×3.3 cm×2.1 cm lucent lesion within the superior lateral left orbital wall with associated remodelling of the adjacent bone and erosion through the left inferior frontal cortex. The lesion caused a mass effect on the eyeball, as well as the superior rectus and levator palpebrae superioris muscles. MRI further characterised the lesion as non-contrast-enhancing, expansile, fluid-filled and mildly hyperintense on T1-weighted and T2-weighted imaging (figure 1A,B).

Figure 1.

T2-weighted MRIs before resection. (A) Axial view showing a supraorbital mass measuring 2.8 cm diagonally and compressing the frontal lobe. (B) Sagittal view showing a supraorbital mass (white arrows) compressing the superior rectus (red arrow) and levator palpebrae superioris muscles (blue arrow).

Treatment

The patient elected surgical resection of the lesion, which was performed through an expanded pterional craniotomy with lateral orbitotomy. Interestingly, while commencing the orbitotomy portion of the craniotomy, we noticed a necrotic and moth-eaten appearance of the supraorbital ridge, which was also the roof of the mass. A greenish-yellow fluid was observed to be oozing from the bone and many small fractures were created during dissection. The fluid was aspirated, and further dissection revealed a yellowish, lobulated and avascular lesion (figure 2), which was resected and sent for pathological analysis along with the previously collected fluid.

Figure 2.

Operative photograph. Solid black arrows identify the yellow lobulated and avascular supraorbital 3.2 cm×3.3 cm×2.1 cm necrobiotic xanthogranuloma exposed post-orbitotomy, just before surgical resection. White arrows identify the necrotic moth-eaten-appearing supraorbital bone adjacent to the lesion.

Outcome and follow-up

Postoperative imaging revealed good resection without complications (figure 3A,B). Papanicolaou staining and microscopic examination of the aspirated cystic fluid revealed rare histiocytes and blood. Histological analysis of the mass revealed predominantly large areas of necrobiotic collagen with numerous cholesterol clefts surrounded by lymphocytes and histiocytes and several multinucleated giant cells (figure 4A,B). This led to the diagnosis of necrobiotic xanthogranuloma, as initially provided by our hospital’s pathology team. Due to this unexpected finding, especially in the absence of cutaneous comorbidities, an independent pathology laboratory was consulted to re-analyse the tissue sample, and the diagnosis was confirmed.

Figure 3.

MRIs after complete mass resection. (A) Axial view of T2-weighted image with red arrows highlighting the fluid-filled residual supraorbital cavity after complete mass resection. (B) Sagittal view of T1-weighted image with red circle indicating fluid-filled residual supraorbital cavity.

Figure 4.

Histopathology slides of necrobiotic granuloma samples from the resected supraorbital mass. (A) Black arrows indicate an area of necrobiotic collagen, and the circled region identifies numerous cholesterol clefts surrounded by lymphocytes and histiocytes (H&E staining, 4×). (B) Black arrow identifying a circled typical multinuclear giant cell (H&E staining, 10×).

After an uneventful postoperative course, the patient was discharged on postoperative day 2. He has continued to do well, with only mild residual blurred vision. Additionally, he has undergone an extensive oncological evaluation for underlying paraproteinemia (including multiple myeloma), lymphoproliferative disorders, and positron emission tomography and CT for possible malignancy. All test results were negative.

Discussion

In this report, we present (to our knowledge) the first case of an intracranial necrobiotic xanthogranuloma in a patient who lacked both the characteristic dermatologic features and an underlying systemic disorder. The nomenclature of necrobiotic xanthogranuloma originated in 1980 and was based on the observed characteristics on physical examination and histological analysis. On physical examination, necrobiotic xanthogranuloma, which is a predominantly cutaneous lesion, is characterised by xanthogranuloma nodules, papules, or plaques with a predilection for the periorbital region.^{1 2} The consensus histological findings, according to board-certified experts and based on review of all 235 known cases, include the presence of granulomas with histoplasmacytic infiltrates and zones of necrobiosis with a variable presence of cholesterol clefts and giant cells.² This matches the histological description of the supraorbital lesion resected in our case, which contained numerous cholesterol clefts associated with multinucleated giant cells, within large areas of necrobiotic collagen (figure 4A,B). This histological diagnosis of necrobiotic xanthogranuloma was initially given by our hospital’s experts and subsequently confirmed by an independent external pathology laboratory that we recruited to verify the diagnosis due to the patient’s unconventional presentation. Importantly, although the lesions leading to the consensus histological description of necrobiotic xanthogranuloma² were primarily of skin origin, the intracranial necrobiotic xanthogranuloma lesion resected in the only published report of an intracranial lesion to date and our case share the same histological characteristics.⁴ This suggest that the supraorbital mass resected in our case was necrobiotic xanthogranuloma.

Beyond histological identity, the supraorbital lesion in our case possesses several other characteristics of necrobiotic xanthogranuloma lesions. The first is its supraorbital location, which is analogous to the periorbital predilection of cutaneous necrobiotic xanthogranuloma lesions.³ Also, the gross yellowish, lobulated and avascular appearance of our supraorbital lesion matches both the consensus description of cutaneous necrobiotic xanthogranuloma lesions and the previously reported intracranial necrobiotic xanthogranuloma.⁴ Importantly, as observed during the procedure, the lesion in our case eroded into the adjacent bones, creating a necrotic and moth-eaten-appearing supraorbital bone. This feature mimics the ulcerative and collagenolytic properties of necrobiotic xanthogranuloma skin lesions.^{1 2 4} Therefore, besides the histological verification, several other features of the lesion described in the present case support the necrobiotic xanthogranuloma diagnosis.

Interestingly, our patient was otherwise healthy and lacked underlying systemic disorders such as paraproteinemia, lymphoproliferative disorders and plasma-cell dyscrasias that are associated with necrobiotic xanthogranuloma. Although the aetiology is poorly understood, existing evidence strongly suggests that necrobiotic xanthogranuloma is secondary to an underlying systemic disorder, as seen in most of the 235 cases reported to date.^{2 3} The most commonly reported comorbidities include paraproteinemia (most commonly IgG-κ), as detected in 82.1%, and a range of malignancies, as reported in 25.1%.^{2 3} As a result, the recently proposed diagnostic criteria for necrobiotic xanthogranuloma requires either cutaneous xanthogranulomatous lesions with periorbital predilection or a paraproteinemia, plasma-cell dyscrasia and/or lymphoproliferative disorder, in addition to clinical presentation and histological confirmation.^{1 2} Our case deviates from these criteria, like the only other known case of an intracranial necrobiotic xanthogranuloma lesion, because both patients lacked underlying systemic comorbidities despite extensive work-up.⁴ However, unlike the other intracranial case, our case further deviates by lacking the dermatologic manifestations of necrobiotic xanthogranuloma. These findings make our case the first report of an isolated intracranial necrobiotic xanthogranuloma lesion, highlighting possible deficits in our understanding of the aetiology and presentation of necrobiotic xanthogranuloma, as well as the need for further investigation to better understand this disorder.

In a recent review of existing systemic treatment options, IVIG, corticosteroids and combination therapies that include corticosteroids were found to be the most effective therapies for necrobiotic xanthogranuloma.³ This conclusion was based on a meticulous review of 175 necrobiotic xanthogranuloma cases with well-documented management and treatment outcomes.³ Our patient remains free of disease at follow up. Therefore, we are continuing observational management while keeping these therapeutic options in mind.

Limitation-wise, we understand that the isolated nature of the intracranial necrobiotic xanthogranuloma lesion in this case is unconventional. This understanding prompted our successful effort to independently verify the histopathology results before documenting this report. Hence, the independent validation strengthens our confidence in the accuracy of the diagnosis and that this case is a rare exception to the consensus diagnosis criteria. Also, we acknowledge that the follow-up period of 10 months since the lesion resection could be considered relatively short and a limitation of this case. However, during this seemingly brief period, the patient underwent exhaustive screening tests independently completed at a comprehensive cancer centre that have all returned negative. In terms of imaging, a whole-body positron emission tomography scan 2 months after the surgical resection procedure was negative for any evidence of disease. Additionally, a quantitative analysis of his serum protein electrophoresis, serum immunoglobulins A, G and M, and kappa and lambda free light chains conducted 5 months after the surgery were also within normal limits. Although these test results, together with the patient’s subjective affirmation of sound health, collectively boost our confidence that this intracranial lesion is an isolated finding, he continues to undergo surveillance follow-up.

Learning points.

• After 40 years of strongly believing that necrobiotic xanthogranuloma is a solely dermatologic condition, our patient’s case suggests otherwise.

• Also, unlike the belief that necrobiotic xanthogranuloma is a dermatologic manifestation of other underlying systemic conditions, we present the first histologically validated case with neither a dermatologic association nor an underlying systemic disorder.

• This report adds to growing evidence of the rare but possible intracranial manifestation of this condition, broadening the potential differential diagnosis for patients who present with neurological findings and suggesting the importance of a comprehensive work-up.

• This case presentation is not in keeping with recently proposed criteria for the diagnosis of necrobiotic xanthogranuloma based on a comprehensive review of all known cases. This case highlights current deficits in our understanding of the aetiology and presentation of necrobiotic xanthogranuloma and the need for further research into this topic.

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