Indian Journal of Pathology and Microbiology

: 2023  |  Volume : 66  |  Issue : 2  |  Page : 366--368

Intravascular papillary endothelial hyperplasia: Olanzapine-induced vascular proliferation?

Shilpi Agarwal, Kavita Gaur, Vishakha Arya 
 Department of Pathology, Lady Hardinge Medical College, New Delhi, India

Correspondence Address:
Kavita Gaur
Department of Pathology, Lady Hardinge Medical College and Associated Hospitals, Shaheed Bhagat Singh Marg, New Delhi - 110 002


Intravascular papillary endothelial hyperplasia (Masson's tumor) is a reactive vascular lesion of obscure etiopathogenesis, often seen in the head and neck. Its presentation as a scalp swelling, however, is extremely uncommon. We describe the first report in an adult, being treated for bipolar illness. A young male presented with a right frontotemporal scalp swelling since 3 weeks. He was also being treated for bipolar illness with olanzapine. Examination revealed a soft, non-pulsatile swelling. After inconclusive aspiration results, a complete excision was performed. Histopathology revealed proliferating endothelial cells arranged as papillary fronds confined to vessel lumina, devoid of atypia, accompanied by thrombosed vessels facilitating a diagnosis of Masson's tumor. The patient is free of recurrence five months after surgery. Further studies on a possible effect of olanzapine on vascular proliferation in experimental in vivo and in vitro models would definitely aid in elucidating clinical relevance, if any.

How to cite this article:
Agarwal S, Gaur K, Arya V. Intravascular papillary endothelial hyperplasia: Olanzapine-induced vascular proliferation?.Indian J Pathol Microbiol 2023;66:366-368

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Agarwal S, Gaur K, Arya V. Intravascular papillary endothelial hyperplasia: Olanzapine-induced vascular proliferation?. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Sep 25 ];66:366-368
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Intravascular papillary endothelial hyperplasia or Masson's tumor is a non –neoplastic reactive lesion comprising of proliferating endothelial cells, confined to vascular lumina. It has been described in the head and neck as well as the skin and subcutis of the extremities.[1] The pathogenesis remains obscure and possibly represents an abnormal pattern of thrombus organization. Masson's tumor (MT) presenting as a scalp swelling is extremely uncommon with only three previous reports, all occurring in children.[2],[3],[4] We describe a case of MT in an adult subject presenting with a scalp swelling. The patient was being treated at our institution for manic depressive illness with olanzapine. To the best of our knowledge, this is the first report of such an association. Herein, we also postulate possible pathogenetic mechanisms operating in this case.

 Case Description

A 28-year-old man presented with a scalp swelling of insidious onset since 3 weeks. There was no history of a change in size of the lesion, pain, fever, swellings elsewhere in the body or trauma. The patient was being treated for manic depressive illness for the last three months and was on a regimen of olanzapine (20 mg once a day) by which his mood swings and sleep cycles improved. The patient was conscious, with intact cognition. No other drugs were being taken by the patient. Examination revealed a right frontotemporal soft swelling measuring 3.0 cm × 2.0 cm [Figure 1]a. The swelling was mobile, fluctuant, nonreducible, and nonpulsating with normal overlying skin. Neurological and visual assessment was unremarkable. Contrast-enhanced computed tomography (CECT) head was normal and did not reveal intracranial extension of the scalp lesion [Figure 1]b. Fine needle aspiration from the swelling showed a few benign plump spindle cells in a hemorrhagic background, suggesting a mesenchymal lesion. The resected tissue showed numerous proliferating endothelial cells arranged as small papillary fronds, devoid of atypia/mitotic activity [Figure 2]a. These fronds remained confined to the vessel lumina accompanied by thrombosed vessels. CD34 immunostain highlighted numerous proliferating endothelial cells [Figure 2]b, [Figure 2]c, [Figure 2]d facilitating a diagnosis of Masson's tumor. Post-surgery, as the patient's mood swings and sleep improved, the patient continued on a dose of 15 mg olanzapine once a day. The patient is currently doing well and is free of recurrence five months after surgery.{Figure 1}{Figure 2}


Masson's tumor, initially described in 1923 as the “Hemangioendothelioma vegetant intravasculaire” is an enigmatic benign vascular lesion, commonly referred to as intravascular papillary endothelial hyperplasia.[1] Though frequent in the head and neck, its presentation as a scalp swelling has been infrequently described with only few prior reports in the literature.[2],[3],[4] Unlike our case, all cases documented previously were in children and displayed intracranial extension.

MT may be of three types based on the setting of origin –de novo, occurring in dilated vascular spaces, mixed occurring in pre-existing benign vascular lesions like hemangioma, arteriovenous malformations, and extravascular, associated with trauma.[4] In our case, there was no pre-existing vascular lesion or history of trauma. As discussed subsequently, the lesion herein may not be a de novo occurrence, hence this case does not fit into any of the originally described categories.

Owing to its soft consistency, clinically MT may simulate any of the soft tissue tumors. FNAC may initially be performed for diagnosis, which in our case was inconclusive. A complete surgical resection is essential in view of its high propensity for recurrence. Histopathology is paramount as MT can be confused with other vascular tumors. Proliferating endothelial cells are intravascular and may be demonstrated immunohistochemically by CD 31, CD 34, VEGF or vWF. Though exuberant proliferation is noted in MT, cellular atypia, mitotic figures, necrosis or an intravascular predilection are not seen unlike angiosarcoma. The absence of atypia excluded Dabska tumor, another intravascular papillary lesion.

An important histological correlate to be observed is the intimate admixture of proliferating endothelial cells with thrombi, as seen in this case. The pathogenesis of this entity remains obscure, some authors postulating a possible cause of trauma and subsequent basic fibroblast growth factor (bFGF) secretion by recruited macrophages.[5] As trauma was absent in our case, this seems an unlikely possibility. Others have mentioned aberrant local hemodynamics and subsequent thrombus formation to be other pathogenetic factors.[6]

Another aspect of this case was that our patient developed MT while being on olanzapine therapy for three months. While this may purely be a temporal association, a recent study on olanzapine in a 3D gel collagen model demonstrated olanzapine to promote angiogenesis by up-regulation of STAT3. Increased mRNA levels of bFGF and VEGFA/B were also noted.[7] Olanzapine is a second-generation antipsychotic used in the treatment of schizophrenia and bipolar disorder. It promotes regional blood flow in the brain in parallel to changes of brain angiogenesis.[8] Described adverse effects include hepatotoxicity and nephrotoxicity, with histological effects on the rat pancreas and kidneys being described only recently.[9] The occurrence of vascular tumors or reactive endothelial proliferation in humans has hitherto been undescribed. Applying the Naranjo scoring system in our case, the adverse drug reaction probability score was 2, indicating, at best, only a “possible” effect, with no direct causal link.[10]

Organic causes of bipolar disorder were ruled out before the initial diagnosis, hence the possibility of the lesion causing psychiatric manifestations was excluded. Our patient is still on olanzapine therapy for bipolar disease, but with an improvement in symptomatology, is now on 15 mg of the drug after receiving the previous dosage of 20 mg for three months. Our patient is on a reduced dosage of olanzapine than before excision. Although he is currently doing well and is free of recurrence five months after excision, further work on larger cohorts would be required to assess the effect of dosage on possible vaso-proliferation.

MT though benign, is often mistaken histologically for vascular tumors, especially when an uncommon presentation comes to the fore, as seen herein. A timely and correct histopathological diagnosis is essential to avoid clinical mismanagement. Further studies on the effect of olanzapine on vascular proliferation in experimental models, as well as retrospective studies of cases on long-term therapy with this drug may be useful in examining any positive/negative association with in vivo vaso-proliferative phenomena of clinical relevance. It is in this context that the present report may prove useful for future research.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


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