case report

Skull Metastasis as a Primary Manifestation in Cervical Carcinoma

Nikolay Tonchev1, Klaus-Peter Stein1, Atanas Ignatov3, Belal Neyazi1, Christian Mawrin2, I. Erol Sandalcioglu1, Ali Rashidi1

1 Department of Neurosurgery, Otto-von-Guericke University Magdeburg, Germany

2 Department of Neuropathology, Otto-von-Guericke University Magdeburg, Germany

3 Department of Gynecology, Otto-von-Guericke University Magdeburg, Germany

*Corresponding author : Nikolay Tonchev, Department of Neurosurgery, Otto-von-Guericke University Magdeburg, Germany

Received Date: 17 November 2022

Accepted Date: 21 November 2022

Published Date: 23 November 2022

Citation : Tonchev N, Stein KP, Ignatov A, Neyazi B, Mawrin C, et al. (2022) Skull Metastasis as a Primary Manifestation in Cervical Carcinoma. Ann Case Report. 7: 1052. DOI: https://doi.org/10.29011/2574-7754.101052

Abstract

Cervical cancer (CC) is one of the most frequent malignant cancers in the female population. Skull and brain metastasis in CC is still a quite rare entity. We present the case of a 62-year-old woman with a primary manifestation of cervical carcinoma (FIGO IIIA) with two concurrent skull bone metastases. Because of increase in the size of the cranial tumors and new onset of neurological deterioration, a complete removal of one of the lesions with histological verification was performed. The microsurgical resection of the exophytic parietal lesion was achieved using a new visualization technique under the exoscope (Olympus Corporation, ORBEYE®). A multidisciplinary approach and combined treatment methods could ensure a better quality of life for patients with metastatic CC.

Introduction

CC is one of the most common cancers in women and affects mostly middle-age women (55-65 years) with increasing incidence after 30 years of age [1, 2]. In Germany, CC has a prevalence of about 1.9%, according to 2018 data [3]. CC spreads locally mainly via the lymphatic system, but hematogenous dissemination can just as easily occur in various organs such as lungs, pelvic and long bones. “ Metastatic cascade” is referred to as a multistep process for the distant spread of cancer [4-7]. Metastasis to the brain usually occurs after a lung preparation [4, 8]. Development of both skull and brain metastasis at the same time is very rare [9]. For the first time we present the case of a patient with two skull bone metastases as a primary manifestation for malignancy and subsequent diagnosis of CC.

Case Report

A 62-year-old patient, para-2, after two spontaneous partus presented in January 2022 with new onset of speech, gait, and tongue movement disturbances for 2 days. Additionally, she described hearing difficulties and an earache for about 2 weeks. Clinical examination revealed a large well-circumscribed lesion on the right parietal side of the head that was known to the patient for more than two months (Figure 1). Previously the described lesion was classified as an atheroma and observation was recommended due to the initial small size and negative history for malignancy.

Because of the rapid volume progression and the new onset of cranial nerve palsies (N. VI, VII, VIII and XII), further diagnostic was initiated at the department of neurology of a local hospital. Computed tomography (CT) demonstrated a right parietal cystic lesion with exophytic growth and bone destruction. An additional lesion was located in the temporal bone, which was responsible for the presented neurologic symptoms. Contrast-enhanced MRI offered better visualization of the tumor, which showed no evidence of other cranial lesions (Figure 1).

Past medical history was negative for malignancies. On primary consultation, the patient described additional blackishbrown vaginal discharge and intermittent bleeding per vaginum. Initial gynecologic examination revealed diffuse, slow bleeding from the entire portio vaginalis, without pelvic pain. The most likely clinical diagnosis turned out to be cervical carcinoma. After completion of radiological diagnostics with chest-abdomen-pelvis CT, the patient was referred to our department for further treatment.

According to multidisciplinary tumor board consensus the patient underwent resection of the exophetic lesion on the right parietal side to accomplish histological verification. The surgical procedure was performed under an exoscope (Figure 2). This technical method provided excellent visualization possibility for all staff members in the operating room, as all colleagues directly observed each step of the operation. A circumferential excision was made around the lesion and the skin was elevated. After detachment of the skin margins, the lesion and cystic lesion were visualized. One burr hole was made and a round bone flap was excised. The cystic component of the lesion appeared to have connection to the periosteum. It was filled with viscous necrotic tissue, which was aspirated. The rest of the tumor capsule was elevated along with the bone flap, and the underlying dura mater became visible (Figure 2). The calvarial bone flap was eroded by the tumor from inside out, and the dura was found to be affected as well, so a complete dural excision, followed by duraplasty, was performed. The bone defect was replaced with a bone cement graft (PALACOS®+G). The pathomorphological examination revealed carcinoma metastasis with most probable origin from cervical cancer (Figure 3).

The biopsy specimen from the gynecologic examination of the cervix revealed poorly differentiated squamous cell carcinoma (G3) and confirmed the diagnosis of cervical cancer, FIGO IIIA, M1. Subsequent palliative stereotactic radiotherapy of both cranial lesions and concomitant radio-/chemotherapy with denosumab of the primary tumor disease was the recommended treatment plan. After completion of neurosurgical therapy, the patient was transferred to the department of obstetrics and gynecology for further treatment.

Figure 1: Exophytic subcutaneous lesion with size of approx. 7x7 cm (a); MRI-T1-weighted images (b), (c) in transversal and coronal sections: Exophytic lesion of the right parietal bone with osteolytic characteristics, contrast enhancement and no infiltration of brain parenchyma. CT (d) and MRI-T1-weighted images (e), (f) in transversal and coronal sections: Osteolytic lesion of the right temporal bone with contrast enhancement and almost no brain oedema.


Figure 2 : Macroscopic images and intraoperative findings: a) Tumour lesion after elevation of the skin flap. Exophytic growth with periosteal elevation and vascularisation can be observed; b) opening of the cystic lesion with necrotic fluid and osteolytic bone edges; c) Craniotomy and bone elevation with a view of the lower tumour-membrane and dura with tissue hyper-proliferation; d) ORBEYEExoscope intraoperative findings: Opening of dura mater with normal underlying brain surface. Front-left: Operators’ view and technical positioning.

 

Figure 3 : Microscopic images of histopathological sample from the cranial skull lesion: 1. Pan-Cytokeratin immune-stain with cytokeratin positive epithelial cells; 2. Squamous cell proliferation with multiple atypical mitoses, H&E stain x100; 3. Immunohistochemistry with Ki67 stain as a cell proliferation marker; 4. malignant glands with several giant cells, H&E stain x200.

Discussion

CC is one of the most common cancers in women especially in developing countries [10]. The vertebrae and pelvic bones are the most frequent sites for skeletal metastases in CC [11, 12]; however, metastasis in CC is generally rare and is associated with a poor prognosis [12, 13]. Multiple cutaneous metastases are indicative of likely uncontrolled and widespread metastatic disease with a poor overall prognosis [14].

Hematogenous spread of CC occurs only in advanced stages of the disease, particularly involving the lungs, liver, bones, and non-regional lymph nodes [1, 9, 15, 16].

Matsuyama et al. described a series of 713 patients with bone metastases, of which only six were in the cranial region [17]. Zilberlich et al. reported a case with a total of 20 months progression-free survival with isolated cranial metastasis from previously treated cervical cancer. Patients with bone metastasis from cervical cancer have a poor prognosis and a prognosis of life expectancy of less than one year [12].

Cisplatin-based combination chemotherapy can be considered in patients with good general health and good renal function [9]. Morgan et al. suggest that denosumab may also be used as second-line immunotherapy for bone metastases because of its bone-stabilizing properties [18].

Table 1 provides an overview list all published in literature cases of patients with cervical carcinoma and secondary diagnosed skull bone metastases. In comparison to this, our patient was primary diagnosed with two cranial metastases because of the neurological manifestation and only after further clinical workup and gynecological biopsy verification the diagnosis of CC was confirmed.

Brain metastases from cervical cancer are extremely rare, with an incidence of 0.57% and diagnosed in up to 96.3% of cases after the diagnosis of CC [19]. The symptoms of brain metastasis in CC are not different from those of other brain metastases. Typical Symptoms present raised intracranial pressure with headache, nausea, and vomiting, followed by local symptoms such as seizures and paralysis, and cranial nerve palsies [19-21]. Brain metastases in CC have poor survival; the mean and median survival periods after diagnosis have been reported to be 7 and 4.6 months, respectively [4, 22].

Multidisciplinary approach should be the treatment strategy for patients with brain metastases from CC. After surgical resection of the metastasis, the preferred therapy choice is whole brain radiotherapy (WBRT) followed by chemotherapy [19].

In accordance with multidisciplinary team consensus, after neurosurgical resection of the skull metastasis, our patient received stereotactic radiotherapy of the brain metastasis followed by chemotherapy with denosumab.

N

Author

Year

Age

Histology

Initial Stage

Primary Treatment

DFP

Treatment of metastasis

Metastatic lesion control

Country

1

Shimizu et al. [23]

1983

59

SCC

IIIB

RT + BT

5 m

none

died after 3 m

Japan

2

Böhme et al. [24]

1990

52

SCC

IIIB

Biopsie + RT

2 m

Biopsie + RT (60Gy/33Fx)

died after 2 m

Germany

3

Yanuck et al. [25]

1991

21

SCC

IV

none

PD

Biopsy + RT (30Gy/10Fx) + QT

died after 1 m

USA

5

Maheshwari et al.[15]

2001

45

SCC

IIB

RT (50Gy/25Fx) + BT

8 m

RT (45Gy/15Fx)

4 m

India

6

Agarwal et al. [9]

2002

60

SCC

IIIB

RT (45Gy/20Fx) + BT

2 m

Biopsy + RT (20Gy/5Fx)

-

India

7

Chung et al. [26]

2007

45

SCC

IB1

TAH + RT + QT

7:00 AM

None

died after 3 m

Japan

8

Abhishek et al. [27]

2008

53

adenocarcinoma

IIA

TAH + RT (28Gy/14Fx)

4 m

Biopsy + RT (30Gy/10Fx) + QT

- (stable at discharge)

India

9

Takagi et al. [16]

2010

48

SCC

IIB

TAH + RT (45Gy/20Fx) + QT

8 m

RT (45Gy/15Fx); without QT

-

Japan

10

Dimitrakopoulos et al. [28]

2010

37

SCC

-

TAH + RT + QT

20 m

Biopsy + RT + QT

6 m

Greece

11

Mohanty et al. [12]

2010

54

SCC

IIIB

RT (50Gy/25Fx) + BT + QT

2 m

Biopsy + RT (30Gy/10Fx) + QT

- (good local control at discharge)

India

12

Vitorino-Araujo et al. [10]

2013

55

SCC

IIIB

-

-

Resection

- (stable at discharge)

Brazil

13

Zilberlicht et al. [29]

2014

58

SCC

IIB

TAH + RT + BT + QT

7 m

Resection + RT

20 m

Israel

14

Rao et al. [30]

2015

62

SCC

IV

-

PD

RT alone

4 m

India

15

Diaz, J F et al. [1]

2019

41

SCC

IIIB

RT (50Gy/25Fx) + BT + QT

18 m

Resection + RT (51Gy/17 Fx)

18 w

Peru

16

Saffarieh et al. [31]

2020

50

SCC

IIB

RT + BT + QT

2:00 AM

Resection + RT + QT

2:00 AM

Iran

17

Morgan et al. [18]

2021

56

SCC

IB2

TAH + RT + QT

1 w

Biopsy + RT (55Gy/25Fx) + QT

8 m

USA

18

Current case

2022

62

SCC

IIIA

Biopsie + RT + QT

PD

Resection + WBRT

3 m (until date of publication)

Germany

Table 1: Overview of all case reports on cervix carcinoma in the literature.

SCC - Squamous cell carcinoma; TAH - Total abdominal hysterectomy; RT - Radiotherapy; BT - Brachytherapy; QT - Concurrent chemotherapy; DFP - Metastasis free period; PD - Primary manifestation with skull metastasis; “-“ no published data; w - Weeks; m - Months; a - Years.

Conclusion

Skull and brain metastases from cervical cancer remain a challenging medical issue. The development of modern technology has the potential to achieve earlier diagnosis and a better management for these tumors. Nevertheless, the overall prognosis of this progressive disease remains relatively poor. Metastatic dissemination represents an aggressive and already advanced tumor stage that limits the overall life expectancy of the affected patients. Surgical resection in combination with radiotherapy and chemotherapy remains the preferred treatment recommendation. The exoscope provides a good intraoperative visualization, so that all members of the surgical team can follow every surgical step simultaneously. This enables also a better teaching technique for the trainee neurosurgeons.

Conflict of interest

The authors do not have any conflicts of interest involved in this research.

Acknowledgments

We would like to express our thanks to the patient, who agreed to contribute to the publishing of this case report and cooperated throughout the whole treatment process.

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