Publications by authors named "Danko Müller"

12 Publications

  • Page 1 of 1

Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

Epithelial to mesenchymal transition (EMT), which is characterized by the reduced expression of E-cadherin and increased expression of N-cadherin, plays an important role in the tumor invasion and metastasis. Classical Wnt signaling pathway has a tight link with EMT and it has been shown that nuclear translocation of β-catenin can induce EMT. This research has showed that genes that are involved in cadherin switch, and , play a role in meningioma progression. Increased N-cadherin expression in relation to E-cadherin was recorded. In meningioma, transcription factors SNAIL, SLUG, and TWIST1 demonstrated strong expression in relation to E- and N-cadherin. The expression of SNAIL and SLUG was significantly associated with higher grades ( = 0.001), indicating their role in meningioma progression. Higher grades also recorded an increased expression of total β-catenin followed by an increased expression of its active form ( = 0.000). This research brings the results of genetic and protein analyzes of important molecules that are involved in Wnt and EMT signaling pathways and reveals their role in intracranial meningioma. The results of this study offer guidelines and new markers of progression for future research and reveal new molecular targets of therapeutic interventions.
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http://dx.doi.org/10.3390/cancers13071633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037732PMC
April 2021

Challenges in the diagnostics and treatment of ectopic ameloblastic carcinoma: a case report.

Croat Med J 2020 Jul;61(3):271-275

Marko Tarle, Department of Oral and Maxillofacial Surgery, University Hospital Dubrava, Gojko Šušak Avenue 6, 10000 Zagreb, Croatia,

Ameloblastic carcinoma (AC) is a rare and aggressive malignant epithelial odontogenic tumor, most commonly located in the mandible or maxilla. An extremely rare extragnathic localization of AC with no connection to the jaws, ectopic ameloblastic carcinoma (EAC), has so far been described only three times. This report presents a 64-year-old male with skull base ameloblastic carcinoma and offers a review of diagnostic and treatment challenges related to EAC. Because of its rarity and histological similarity to other tumors, EAC is often misdiagnosed. This is why we established a pathohistological and immunohistochemical profile of EAC that differentiates it from histologically similar tumors. The most frequently used EAC treatment is radical surgical resection, but the majority of reviewed reports described local recurrence. Taking into consideration new scientific discoveries on the molecular pathogenesis of ameloblastoma, we are the first to have performed BRAF mutation analysis in an EAC patient. BRAF inhibitors offer promising results in the treatment of BRAF-positive ameloblastomas and should continue to be researched in AC and EAC patients. Finally, EAC should be considered in differential diagnosis of head and neck tumors outside the jaws.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358694PMC
July 2020

Prognostic significance of bone morphogenetic protein 6 (BMP6) expression, clinical and pathological factors in clinically node-negative oral squamous cell carcinoma (OSCC).

J Craniomaxillofac Surg 2019 Jan 10;47(1):80-86. Epub 2018 Nov 10.

University of Zagreb School of Medicine, Department of Maxillofacial Surgery, University Hospital Dubrava, Avenue Gojko Susak 6, 10000, Zagreb, Croatia. Electronic address:

Bone morphogenetic protein 6 (BMP6) has unique properties regarding structure and function in supporting bone formation during development and adult life. Despite its known role in various malignant tumors, the prognostic significance of BMP6 expression in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the study was to investigate immunohistochemical expression of BMP6 in OSCC in correlation with clinical and pathological parameters, disease recurrence and survival. In addition, we investigated other parameters in order to identify prognosticators of neck metastases and final outcome. The study included 120 patients with clinically T1-3N0 OSCC who were primarily surgically treated between 2003 and 2008. There were 99 (82.5%) male and 21 (17.5%) female patients. The five-year disease-specific survival for the whole cohort was 79.7%. Tumors smaller than 2 cm in diameter showed higher incidence of strong BMP6 expression. No statistical correlation was observed between other clinico-pathological factors and BMP6 expression. Expression of BMP6 was not associated with disease recurrence and survival. BMP6 may not serve as prognosticator of final outcome or recurrence in clinically node-negative OSCC subjects. In multivariate analysis predictors of poorer survival were positive surgical margin, moderate tumor cell differentiation and pathological involvement of levels IV and/or V.
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http://dx.doi.org/10.1016/j.jcms.2018.10.003DOI Listing
January 2019

Intraspinal calcinosis mimicking intervertebral disc extrusion: A clinical and surgical case report.

Surg Neurol Int 2018 14;9:166. Epub 2018 Aug 14.

Department of Neurosurgery, Dubrava University Hospital, Zagreb, Croatia.

Background: Subcutaneous calcinosis is a well-recognized manifestation of systemic sclerosis that usually involves multiple pressure points and may also be found in the paraspinal or intraspinal regions. In this case, intraspinal calcinosis uniquely led to a severe neurological deficit.

Case Description: A patient with severe systemic sclerosis/calcinosis exhibited left greater than right lower extremity radiculopathy attributed to intraspinal left-sided L4-L5 calcinosis. On examination, the patient exhibited bilateral positive Lasegue signs, distal lower extremity weakness (left greater than right), and bilaterally decreased Achilles responses. When the magnetic resonance imaging (MRI) revealed a significant intracanalicular mass on the left side at the L4-L5 level, the patient underwent a left-sided L4-L5 decompressive laminectomy. The MRI scan 5 years later revealed no recurrence of the calcinosis, and the patient had no residual neurological deficit.

Conclusions: Spinal calcinosis rarely involves the lumbar spinal canal. Here, a patient with a large left-sided L4-L5 focus of intraspinal calcinosis, mimicking a disc herniation, required a laminectomy to resect the lesion. Lumbar calcinosis should be radiologically evaluated utilizing using X-ray, MRI, and computed tomography studies to adequately document the pathology. Patients, when symptomatic, may require surgical decompression and excision of these lesions.
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http://dx.doi.org/10.4103/sni.sni_147_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108162PMC
August 2018

Primary dural lymphoma mimicking meningioma: a clinical and surgical case report.

J Surg Case Rep 2018 Aug 6;2018(8):rjy189. Epub 2018 Aug 6.

Department of Neurosurgery, University Hospital Dubrava, Zagreb, Croatia.

Introduction: Primary central nervous system lymphoma and its subtype, primary dural lymphoma, are types of non-Hodgkin's lymphoma that only occur in the central nervous system without any dissemination. They are extremely rare cases of extra nodal lymphomas accounting for 1--5% of intracranial tumors.

Case Report: We present a patient diagnosed with primary dural lymphoma in right frontal brain region who underwent surgical resection. Histopathological analysis revealed diffuse B-type large cell non-Hodgkin lymphoma. Patient underwent four cycles of R-CHOP and intrathecal methotrexate protocol. Six months postoperative, no signs of newly onset infiltration were present.

Discussion: Primary dural lymphoma most likely presents with unusual radiological signs, which can easily be mistaken for meningioma, the main differential diagnosis. A thorough immunological, histopathological and clinical patients profile should be conducted in order to establish the certainty of diagnosis. Although there are few treatment options: surgery, radiotherapy or chemotherapy, there is no established treatment protocol.
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http://dx.doi.org/10.1093/jscr/rjy189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077807PMC
August 2018

Calcifying epithelial odontogenic tumor of the maxilla (Pindborg tumor).

Coll Antropol 2012 Nov;36 Suppl 2:205-8

University of Zagreb, Dubrava University Hospital, Department of Pathology, Zagreb, Croatia.

Calcifying epithelial odontogenic tumor (CEOT), or the Pindborg tumor, is very rare neoplasm, which accounts up to 1% of all odontogenic tumors. These tumors involve mandible almost twice as common as the maxillary bone, mostly in the premolar and molar region and present at first with local swelling. There is no gender predilection and the tumor usually appears between 2nd and 6th decade of life. We report the case of a 36-year-old male patient with a Pindborg tumor in the maxillary region on the right side, also involving the adjacent maxillary sinus, with destroying of the local anatomical structures. Complete surgical excision of the tumor has been performed and four years after surgical treatment, there is no sign of recurrence.
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November 2012

Multiple cystic brain metastases from papillary thyroid carcinoma mimicking neurocysticercosis.

Int J Surg Pathol 2013 Aug 24;21(4):390-3. Epub 2013 Jan 24.

Department of Neurology, University Hospital Dubrava, Avenija Gojka Šuška 6, 10000 Zagreb.

The papillary carcinoma of the thyroid gland is the most common type of tumor of the thyroid gland with good prognosis and low incidence of distant metastasis. The brain metastases of thyroid gland carcinoma are extremely rare. We report a patient with multiple cystic brain lesions and satisfying criteria for diagnosis of neurocysticercosis. Brain biopsy revealed brain metastases from papillary thyroid carcinoma. The tumor originated from mediastinal thyroid tissue. Even in cases when neuroimaging suggests neurocysticercosis with great accuracy, it is important to exclude metastasis. Extensive brain metastases of primary papillary thyroid carcinoma are extremely rare.
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http://dx.doi.org/10.1177/1066896912473353DOI Listing
August 2013

Renal cell carcinoma with concurrent urothelial carcinoma of urinary bladder and non-Hodgkin lymphoma.

Coll Antropol 2012 Sep;36(3):1049-52

Dubrava University Hospital, Department of Pathology, Zagreb, Croatia.

We report a case of a 71-year-old male with multiple primary malignancies involving kidney and urinary bladder, combined with synchronous lymphoma. The patient was admitted to the hospital because of painless gross hematuria. Examination revealed tumor of the right kidney and papillary tumor in the urinary bladder and enlarged lymph nodes along aorta and inferior vena cava. Transurethral resection of bladder tumor (TUR), radical nephrectomy of the right kidney and retroperitoneal lymphadenectomy were performed. Pathohistologic evaluation, together with immunohistochemistry, gave the patient the final diagnosis of renal cell carcinoma (RCC), urothelial carcinoma of the urinary bladder and B- small cell Non-Hodgkin lymphoma (B-CLL).
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September 2012

Melanotic neuroectodermal tumour of infancy: report of two cases and review of the literature.

J Craniomaxillofac Surg 2012 Jun 6;40(4):e103-7. Epub 2011 Jul 6.

Institute of Pathology, University of Zagreb, School of Medicine, Zagreb, Croatia.

Melanotic neuroectodermal tumour of infancy (MNTI) is an uncommon tumour affecting predominantly the craniofacial bones of the newborn infants. The neural crest origin of the tumour has been confirmed. MNTI is generally accepted as a benign tumour despite of its rapid and locally infiltrative growth. Recurrence rate varies between 10% and 60%, and malignant behaviour has been reported in 6.5% of MNTIs. Systematic review of the literature revealed 445 MNTIs published between 1918 and 2010. We present additional two cases of MNTI from our Department, typical in all terms, which equals a total number of 447 reported cases. One of our cases revealed histological features consistent with malignant behaviour, but at present, 18 months after the surgical excision, there is no evidence of recurrence. Biological behaviour of MNTI cannot be predicted by gross or histologic characteristics, thus early diagnosis and careful follow-up after the complete surgical excision is required.
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http://dx.doi.org/10.1016/j.jcms.2011.05.013DOI Listing
June 2012

Schwannoma of the tongue in a child.

J Craniomaxillofac Surg 2011 Sep 30;39(6):441-4. Epub 2010 Oct 30.

Department of Maxillofacial Surgery, University of Zagreb School of Medicine, University Hospital Dubrava, Avenue Gojko Susak 6, 10000 Zagreb, Croatia.

A schwannoma or neurilemmoma is a benign, slow growing, usually solitary and encapsulated tumour originating from Schwann cells of the nerve sheath. Approximately 25-40% of all schwannomas are seen in the soft tissues of the head and neck, often originate from the acoustic nerve. Intraoral schwannomas are rare and account for 1% of schwannomas of the head and neck region. We report the case of a 10-year-old boy diagnosed with a schwannoma of the tongue. The purpose of this report is to emphasize the possibility of diagnosing schwannoma among all other lingual lesions in children. The disease itself was diagnosed histologically after complete surgical excision. Five years after surgical treatment, the patient is without signs of recurrence. This paper highlights the importance of a multidisciplinary approach in the diagnosis and surgical treatment of this very rare entity.
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http://dx.doi.org/10.1016/j.jcms.2010.10.004DOI Listing
September 2011

Fine needle aspiration cytology of chondroid syringoma.

Coll Antropol 2010 Jun;34(2):687-90

Department of Clinical Cytology and Cytometry, Dubrava University Hospital, Zagreb, Croatia.

Chondroid syringoma (CS) is a rare, benign, appendageal tumor with diagnostic feature of myxochondroid stroma supporting eccrine and apocrine epithelial structures. The usual presentation is a painless, slowly growing mass, typically located in the head and neck region. It usually affects middle-aged and older male patients. Because of its unremarkable clinical presentation it is often overlooked. It should be included in the differential diagnosis of cutaneous head and neck tumors, especially in middle-aged men. Optimal treatment of CS is total surgical excision. We present a 63 year-old man with a small nodule on the neck with 5 years of duration. The diagnosis was made initially on fine needle aspiration cytology that was performed by ultrasound guidance and confirmed subsequently by histology. FNA cytology may be very useful to determine diagnosis before excision.
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June 2010

The rise in melanoma incidence in Croatia.

Acta Dermatovenerol Croat 2002 Mar;10(1):3-7

Clinical Department of Dermatovenerology, Sestre milosrdnice University Hospital, Vinogradska cesta 29, 10 000 Zagreb, Croatia.

The incidence of skin cancer, and particularly of cutaneous melanoma, has increased substantially over the recent decades. It has generally been assumed that early diagnosis may in fact be responsible for a part of incidence increase. The aim of the study was to analyze the prevalence and distribution of primary cutaneous melanoma among biopsy specimens during the 1991-2000 period. The Surgical Pathology computerized registry was used to identify patients with primary cutaneous melanoma. The distribution of primary cutaneous melanoma according to Clark showed an increased number of melanoma in situ diagnosed during the 1997-2000 period. It could not be definitely concluded whether these data resulted from more common excision of suspicious pigmented skin lesions or there was an increase in the melanoma rate as a consequence of environmental changes. Fortunately, nowadays new patients with cutaneous melanoma are mostly diagnosed early in the clinical course of disease when it can be successfully managed by simple surgical treatment.
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March 2002