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  1. Hussaini HM, Angel CM, Speight PM, Firth NA, Rich AM
    Head Neck Pathol, 2012 Dec;6(4):471-5.
    PMID: 22427262 DOI: 10.1007/s12105-012-0350-y
    The hallmark of the histology of epithelial-myoepithelial carcinoma (EMC) is the presence of a regular repetitive mixture of bilayered duct-like structures with an outer layer of myoepithelial cells and inner ductal epithelial cells. Clear cell change in the myoepithelial component is common, but clearing of both cell types, giving an impression of a monocellular neoplasm, is rare. A parotid biopsy was received from an 83-year-old male and subject to routine histologic processing for conventional staining and immunohistochemistry. The encapsulated tumour was composed of sheets of PAS/diastase negative clear cells, separated by fibrous septae. The clear myoepithelial cells were positive for S-100 protein, SMA, and p63 and negative for CK19 and surrounded CK19-positive luminal cells. It is important to utilise immunohistochemistry to differentiate this tumour from others with a similar histologic pattern. Information about the behaviour of the double-clear EMC is limited since there are few cases reported.
  2. Jayasooriya PR, Abeyasinghe WAMUL, Liyanage RLPR, Uthpali GN, Tilakaratne WM
    Head Neck Pathol, 2021 Jul 19.
    PMID: 34282559 DOI: 10.1007/s12105-021-01358-w
    Adenoid ameloblastoma is a hybrid odontogenic tumour showing histopathological features of both ameloblastoma and adenomatoid odontogenic tumour (AOT), with approximately 40 cases reported in the literature. The aims of the report are to illustrate the diagnostic challenges of adenoid ameloblastoma using three new cases and to analyze evidence in literature to consider adenoid ameloblastoma as a new sub type of ameloblastoma. A literature review was performed with the key words-adenoid ameloblastoma, hybrid/composite odontogenic tumours, hybrid ameloblastoma and adenomatoid odontogenic tumour, ameloblastoma with inductive changes, dentinoid and dentinoma to select the cases compatible with the diagnosis of adenoid ameloblastoma. Out of the 40 cases reported in literature, 31 cases with sufficient information and 3 new cases were analyzed. Out of the 34 adenoid ameloblastomas majority of tumours (76.5%) occurred in adults with age ranging from 25 to 55 years. Slight female predilection with a male:female ratio of 0.9:1 was observed. Approximately, 64.7% occurred in the mandible. Radiologically, 82.4% of adenoid ameloblastomas presented as radiolucent lesions while 47.1% occurred with ill-defined margins and cortical perforation at diagnosis. Histopathologically, 70.8% of tumours presented as plexiform ameloblastomas, while duct like structures/glandular structures were the commonest feature supportive of adenomatoid odontogenic tumour observed in overwhelming majority of 95.9% of adenoid ameloblastomas. 91.6% of tumours showed inductive change in the form of dentinoid. Further, 45.4% of the tumours developed at least one recurrence following surgical excision. The report presents literature review based evidence to show the existence of adenoid ameloblastoma, which is demographically similar to conventional ameloblastoma but with histopathological differences and presenting with higher rate/multiple recurrences, indicating its biological aggressiveness. Thus, we would like to propose the inclusion of adenoid ameloblastoma as a sub type of ameloblastoma in the next revision of the WHO odontogenic tumour classification.
  3. Nelson BL, Bischoff EL, Nathan A, Ma L
    Head Neck Pathol, 2020 Jun;14(2):512-515.
    PMID: 31823215 DOI: 10.1007/s12105-019-01108-z
    Lymphangiomas are rare, congenital malformations of the lymphatic system which have a marked predilection for the head and neck. In this region, they most commonly occur on the dorsum of the tongue, followed by the lips, buccal mucosa, soft palate, and floor of the mouth. Lymphangiomas of the tongue are commonly present at birth; however, they may go unnoticed until after eruption of the dentition or even puberty. They may present as a defined mass or as macroglossia with impaired speech, difficulty in mastication, and, in extreme cases, airway obstruction. Clinically, lymphagiomas of the tongue are characterized by clusters of pebbly, vesicle-like nodules. A benign proliferation of lymphatic vessels is identified histologically. A classic case of a lymphangioma of the dorsal tongue is presented.
  4. Rawal SY, Rawal YB
    Head Neck Pathol, 2018 Mar;12(1):123-126.
    PMID: 28589436 DOI: 10.1007/s12105-017-0827-9
    A 70-year-old male presented with a slow growing, dome shaped and painless mass of the hard palate. The mass was excised. Histopathological examination confirmed the diagnosis of a angioleiomyoma (vascular leiomyoma). A leiomyoma is an uncommon benign tumor of smooth muscle differentiation. True leiomyomas of the oral cavity are rare and most oral tumors are derived from the smooth muscle of walls of blood vessels. Therefore, they are called vascular leiomyomas or angioleiomyomas. Clinically, they may resemble a myriad other conditions both benign and malignant. A definitive diagnosis depends upon histopathological examination of the biopsied tissue in correlation with the tumor cell immunohistochemistry. Tumors are excised and recurrence is rare. The histopathological findings and differential diagnosis of a case of a palatal angioleiomyoma are discussed.
  5. Muller S, Tilakaratne WM
    Head Neck Pathol, 2022 Mar;16(1):54-62.
    PMID: 35312982 DOI: 10.1007/s12105-021-01402-9
    The fifth chapter of the upcoming fifth edition of the 2022 World Health Organization Classification of Tumours of the Head and Neck titled Tumours of the oral cavity and mobile tongue, has had some modifications from the 2017 fourth edition. A new section "Non-neoplastic Lesions", introduces two new entries: necrotizing sialometaplasia and melanoacanthoma. The combined Oral potentially malignant disorders and Oral epithelial dysplasia section in the 2015 WHO has now been separated and submucous fibrosis and HPV-associated dysplasia are also discussed in separate sections. Carcinoma cuniculatum and verrucous carcinoma are described in dedicated sections, reflecting that the oral cavity is the most common location in the head and neck for both these entities which have distinct clinical and histologic features from conventional squamous cell carcinoma. This review summarizes the changes in Chapter 5 with special reference to new additions, deletions, and sections that reflect current clinical, histological, and molecular advances.
  6. Abidin NFZ, Rahman FA, Tuck Choon K, Tilakaratne WM
    Head Neck Pathol, 2023 Sep;17(3):821-825.
    PMID: 37209302 DOI: 10.1007/s12105-023-01560-y
    BACKGROUND: EBV-associated smooth muscle tumors (EBV-SMTs) are rare and typically develop in individuals with a compromised immune system, particularly those who have acquired immunodeficiency syndrome (AIDS) or who have undergone organ transplants.

    METHODS: We document a case of EBV-SMT in an HIV-positive 25-year-old man. The lesion was incised and assessed histologically and a panel of immune markers were performed. EBV association was demonstrated by in situ hybridization for EBV-encoded RNA (EBER-ISH).

    RESULTS: Microscopically, the tumor composed of mildly pleomorphic, ovoid to spindled cells with numerous slit-like vascular channels. The tumor cells exhibited diffuse and strong immunoreactivity for smooth muscle actin (SMA) and focal positivity for h-caldesmon. EBER-ISH of the tumor cells revealed strong positive nuclear signals.

    CONCLUSION: The histopathological features of EBV-SMT do not conform to either benign or malignant SMTs and it has a peculiar predilection to develop at sites unusual for leiomyoma or leiomyosarcoma. The key diagnostic features of EBV-SMT include history of immunosuppression, histologic evidence of primitive and mildly pleomorphic cells maintaining blunt nuclear features in most areas, and positivity for EBER-ISH.

  7. Awang Hasyim N, Ismail S, Ling XF, Tilakaratne WM
    Head Neck Pathol, 2023 Sep;17(3):731-738.
    PMID: 36997684 DOI: 10.1007/s12105-023-01545-x
    BACKGROUND: Odontogenic carcinosarcoma (OCS) is an exceptionally rare malignant mixed odontogenic neoplasm, which mostly arises from recurrent benign odontogenic tumour that undergoes malignant transformation.

    METHODS: A literature review was conducted using the keyword of "Odontogenic carcinosarcoma" and all relevant articles were screened. The data collected include demographic profile (age, gender), clinical information (symptoms, location, size), radiologic features, histopathological examination, management, recurrence, metastases, and survival status.

    RESULTS: A total of 17 OCS cases including a new case from our hospital. The incidence of OCS was highest in the third decades of life with predilection for male and posterior region of mandible. Clinically, patients may present with swelling and neurological symptoms. Radiographic examination often showed radiolucency with ill-defined border. This tumour demonstrates an aggressive behaviour with reported cases of distant metastases to the lung, lymph nodes, rib, and pelvis. Here, we report an interesting case of OCS in a 38-year-old man with a previous diagnosis of ameloblastoma. The patient was diagnosed with ameloblastoma but refused surgical intervention and returned after 10 years with rapidly enlarging mass on the right side of mandible. Microscopically, the lesion appears as biphasic odontogenic tumour with malignant cytological features seen in both epithelium and mesenchymal components. The spindle to round mesenchymal tumour cells were only positive for vimentin. Ki67 proliferation index was high in both epithelium and mesenchymal components.

    CONCLUSION: This case showed the tendency of untreated ameloblastoma to undergo malignant changes in the long term.

  8. Hii EPW, Ramanathan A, Pandarathodiyil AK, Wong GR, Sekhar EVS, Binti Talib R, et al.
    Head Neck Pathol, 2023 Mar;17(1):218-232.
    PMID: 36344906 DOI: 10.1007/s12105-022-01481-2
    BACKGROUND: Homeobox genes play crucial roles in tooth morphogenesis and development and thus mutations in homeobox genes cause developmental disorders such as odontogenic lesions. The aim of this scoping review is to identify and compile available data from the literatures on the topic of homeobox gene expression in odontogenic lesions.

    METHOD: An electronic search to collate all the information on studies on homeobox gene expression in odontogenic lesions was carried out in four databases (PubMed, EBSCO host, Web of Science and Cochrane Library) with selected keywords. All papers which reported expression of homeobox genes in odontogenic lesions were considered.

    RESULTS: A total of eleven (11) papers describing expression of homeobox genes in odontogenic lesions were identified. Methods of studies included next generation sequencing, microarray analysis, RT-PCR, Western blotting, in situ hybridization, and immunohistochemistry. The homeobox reported in odontogenic lesions includes LHX8 and DLX3 in odontoma; PITX2, MSX1, MSX2, DLX, DLX2, DLX3, DLX4, DLX5, DLX6, ISL1, OCT4 and HOX C in ameloblastoma; OCT4 in adenomatoid odontogenic tumour; PITX2 and MSX2 in primordial odontogenic tumour; PAX9 and BARX1 in odontogenic keratocyst; PITX2, ZEB1 and MEIS2 in ameloblastic carcinoma while there is absence of DLX2, DLX3 and MSX2 in clear cell odontogenic carcinoma.

    CONCLUSIONS: This paper summarized and reviews the possible link between homeobox gene expression in odontogenic lesions. Based on the current available data, there are insufficient evidence to support any definite role of homeobox gene in odontogenic lesions.

  9. Patel S, Wald AI, Bastaki JM, Chiosea SI, Singhi AD, Seethala RR
    Head Neck Pathol, 2023 Jun;17(2):467-478.
    PMID: 36746884 DOI: 10.1007/s12105-023-01524-2
    BACKGROUND: Secretory myoepithelial carcinomas (SMCA) are rare, mucinous, signet ring predominant tumors with primitive myoepithelial features. While many mucinous salivary gland tumors have now been molecularly characterized, key drivers in SMCA have yet to be elucidated. Recently, NKX3.1, a homeodomain transcription factor implicated in salivary mucous acinar development was also shown in a subset of salivary mucinous neoplasms, salivary intraductal papillary mucinous neoplasms (SG-IPMN). To date, NKX3.1 expression has not been characterized in other mucinous salivary lesions. Here, we report molecular and extended immunophenotypic findings in SMCA and NKX3.1 expression in the context of other head and neck lesions.

    METHODS: We retrieved 4 previously reported SMCA, performed additional immunohistochemical and targeted next-generation sequencing (NGS). We also investigated the use of NKX3.1 as a marker for SMCA in the context of its prevalence and extent (using H-score) in a mixed cohort of retrospectively and prospectively tested head and neck lesions (n = 223) and non-neoplastic tissues (n = 66).

    RESULTS: NKX3.1 positivity was confirmed in normal mucous acini as well as in mucous acinar class of lesions (5/6, mean H-score: 136.7), including mucinous adenocarcinomas (3/4), SG-IPMN (1/1), and microsecretory adenocarcinoma (MSA) (1/1). All SMCA were positive. Fluorescence in situ hybridization for SS18 rearrangements were negative in all successfully tested cases (0/3). NGS was successful in two cases (cases 3 and 4). Case 3 demonstrated a PTEN c.655C>T p.Q219* mutation and a SEC16A::NOTCH1 fusion while case 4 (clinically aggressive) showed a PTEN c.1026+1G>A p.K342 splice site variant, aTP53 c.524G>A p.R175H mutation and a higher tumor mutation burden (29 per Mb). PTEN immunohistochemical loss was confirmed in both cases and a subset of tumor cells showed strong (extreme) staining for P53 in Case 4.

    CONCLUSION: Despite a partial myoepithelial phenotype, SMCA, along with mucinous adenocarcinomas/SG-IPMN and MSA, provisionally constitute a mucous acinar class of tumors based on morphology and NKX3.1 expression. Like salivary mucinous adenocarcinomas/SG-IPMN, SMCA also show alterations of the PTEN/PI3K/AKT pathway and may show progressive molecular alterations. We document the first extramammary tumor with a SEC16A::NOTCH1 fusion.

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