Lingual Tumors Research Articles

Lingual neoplasia in nonhuman primates: Description of five cases and a literature review.

Documentation of lingual tumors is scarce in nonhuman primates. Through a multi-institutional retrospective study we compile cases of primary and metastatic neoplasia in non-human primates. We describe five cases of lingual neoplasia. Three cases are primary lingual tumors: chondro-osteoblastic lipoma in a howler monkey, squamous cell carcinoma, and fibroma in two baboons. We describe two cases of metastatic lymphoma in the tongue in rhesus macaques. A literature review of published lingual neoplasia in nonhuman primates is included in this manuscript. Lingual neoplasia is seldom reported in non-human primates.

Mixed Heterotopic Gastrointestinal/Respiratory Oral Cysts in Newborns: From Prenatal Diagnosis to Histopathological and Therapeutic Management: A Case Report and Literature Review

Fetal lingual tumors are very rare, and their early prenatal diagnosis is important for defining the subsequent therapeutic strategy. In this study, we aimed to describe a case of a congenital septate lingual cyst and perform an extensive literature review on two main databases (PubMed, Web of Science), analyzing the clinical manifestations, the imaging appearance, the differential diagnosis, and particularities regarding the treatment of these tumors. The electronic search revealed 17 articles with 18 cases of mixed heterotopic gastrointestinal/respiratory oral epithelial cysts that met the eligibility criteria and were included in this review. The clinical case was diagnosed prenatally during second-trimester screening. On the eighth day of life, the fetus underwent an MRI of the head, which revealed an expansive cystic process on the ventral side of the tongue with the greatest diameter of 21.7 mm, containing a septum of 1 mm inside. On the 13th day of life, surgery was performed under general anesthesia, and the lingual cystic formation was completely excised. The postoperative evolution was favorable. The histopathological examination revealed a heterotopic gastric/respiratory-mixed epithelial cyst with non-keratinized respiratory, gastric squamous, and foveolar epithelium. The lingual cyst diagnosed prenatally is an accidental discovery, the differential diagnosis of which can include several pathologies with different degrees of severity but with a generally good prognosis.

Abstract 3537: A novel orthotopic xenograft model of spontaneous metastasis for rhabdomyosarcoma using lingual intramuscular injection

Abstract Rhabdomyosarcoma (RMS), a cancer characterized by the defective differentiation of skeletal muscle precursor cells, is the most common pediatric soft tissue sarcoma. Despite significant efforts to characterize the transcriptomic and genetic abnormalities of the disease, the prognosis for patients with advanced or refractory disease has remained unchanged for more than four decades. Preclinically, studies have been hampered by insufficient animal models. For example, the hindlimb orthotopic model, an injection into the gastrocnemius muscle of immunocompromised mice, produces highly encapsulated, non-invasive, non-metastatic tumors. While this model has shown a reasonable recapitulation of tumor proliferation response, investigators using this model are unable to assess the effect of their investigational treatment on local invasion or distant metastasis. Moreover, transgenic mouse models of RMS, while commonly metastatic, diverge significantly from the transcriptomic signature of human tumors. With these considerations, we hypothesized that an alternative orthotopic site, the tongue, may provide a more representative xenograft model of RMS. In a proof of principal experiment, the fusion negative RMS (FN-RMS) cell line RD was injected into the skeletal muscle of the tongue, a lingual intramuscular (LIM) injection. Tongue tumors establish in approximately 60-80% of mice injected within approximately 40 days. By histopathology, the primary tumors show evidence of local invasion. Interestingly, approximately 60% of these tumors also spread to local cervical lymph nodes, a process not observed in hindlimb orthotopic models or subcutaneous models. We expanded our investigation to include additional FN-RMS cell lines: RMS-YM, SMS-CTR, and a MEK inhibitor resistant cell line CTR-557. Mice injected with RMS-YM cells established tumors in at least 60% of mice by 75 days post injection. Additionally, enlarged local and distant lymph nodes are observed in 50% of these mice. Intriguingly, mice injected with SMS-CTR or its MEK inhibitor resistant derivative, CTR-557, frequently have tumors in both local and distant lymph nodes without evidence of a primary tongue tumor. One mouse in each group also had pulmonary metastases. Taken together, this model not only demonstrates the first orthotopic xenograft model of spontaneous metastasis for FN-RMS, it also mimics the spread of disease that is observed clinically in RMS originating in the head and neck. Ongoing and future studies include 1) generating highly metastatic human FN-RMS cell lines; 2) using spatial transcriptomics to compare the tumor microenvironment of non-metastatic hindlimb tumors and invasive and/or metastatic lingual tumors; and 3) identifying drivers of FN-RMS dissemination through transcriptomic, genome accessibility, and phospho-proteomic methods. Citation Format: Katie E. Hebron, Kristine Isanogle, Amy James, Simone Difilippiantonio, Marielle E. Yohe. A novel orthotopic xenograft model of spontaneous metastasis for rhabdomyosarcoma using lingual intramuscular injection. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3537.

Survival rates of patients with tumors originating in different segments of the left upper lung in stage I to III non-small cell lung cancer.

BackgroundThe aim of this research was to evaluate the effect of spatial location of tumors on the prognosis of patients with left upper lung non-small cell lung cancer (NSCLC), with a focus on the S1+2+3 and lingual segment.MethodsA total of 486 patients who underwent lobectomy and systematic lymph node dissection were collected retrospectively in this study (354 S1+2+3 and 132 lingual segment patients). Factors impacting survival were assessed via univariate analyses, multivariate analyses, and log-rank tests.ResultsCompared with tumor location in S1+2+3, lingual segment tumor location of stage II to III left upper lung NSCLC patients was significantly associated with a better 5-year disease-free survival (DFS) (P=0.041). Multivariate analysis results showed that tumor location in the lingual segment was a good independent prognostic factor of stage II to III left upper lung NSCLC patients [hazard ratio (HR) =0.602, 95% confidence interval (CI): 0.149–0.865, P=0.006). However, in stage I left upper lung NSCLC, tumor location (HR =1.069, 95% CI: 0.571–2.000, P=0.835) was not an independent prognostic factor, and only T2 (HR =2.422, 95% CI: 1.271–4.620, P=0.007) was an independent worse prognosis factor.ConclusionsTumor location in the lingual segment of left upper lung stage II to stage III NSCLC is a good independent prognostic factor compared with S1+2+3. Nevertheless, tumor location does not impact the prognosis of patients with stage I NSCLC in the left upper lung.

Tongue Schwannoma: A Clinicopathologic Study of 19 Cases.

Schwannomas commonly occur in the head and neck but infrequently involve the oral cavity and rarely affect the tongue. The clinical and pathologic features of 19 cases of schwannoma arising in the tongue were analyzed. There were 13 males and 6 females ranging in age from 12 to 82years (mean 34years; median 29years). The majority of tumors presented as an asymptomatic mass localized to the anterior two-thirds of the tongue. Histologically, 18 schwannomas exhibited characteristic Antoni A and B areas with the former pattern predominating. One tumor was composed exclusively of cellular Antoni A tissue and was classified as a cellular schwannoma. Tumor encapsulation was variable with nearly half of the lesions lacking a well-defined fibrous capsule. All were strongly and diffusely positive for S-100 protein. No recurrences were observed on clinical follow-up. Schwannoma of the tongue, although rare, should be separated from other types of lingual nerve sheath proliferations and tumors.

HPV insertional pattern as a personalized tumor marker for the optimized tumor diagnosis and follow-up of patients with HPV-associated carcinomas: a case report

BackgroundIn clinical oncology, only a few applications have been developed using HPV as a personalized tumor marker, a lack most probably related to the limited information obtained by the classical Polymerase Chain Reaction (PCR) approach. To overcome this limitation, we have recently developed the capture-based Next-Generation Sequencing (NGS) “CaptHPV” assay, designed to provide an extensive and comprehensive molecular characterization of HPV DNA sequences associated with neoplasias, ie the sequence of the viral genome (245 genotypes), its physical state, viral load, integration site and genomic alterations at integration locus. These data correspond to highly specific tumor markers that can be used to improve diagnosis and patient’s follow-up.Case presentationWe report here a case that is a straightforward and practical illustration of the power of the CaptHPV method. A patient developed successively a carcinoma of the anal canal and of the tongue. The two tumors were squamous cell carcinoma, found associated with HPV16 using PCR. In order to document a possible metastasis to the tongue from the anal cancer, we performed CaptHPV analysis on the two tumors. The analysis of the anal carcinoma found 55 viral/human hybrid reads allowing the identification of the HPV16 DNA integration in the 4q25 chromosomal band locus with a 178,808 bp deletion in the cell genome. Molecular analysis of the tongue tumor disclosed 6110 reads of HPV16, with a viral pattern strictly identical to that of the anal tumor. A total of 131 hybrid reads between HPV16 and the cell genome were found, corresponding exactly to the same locus of integration of viral DNA at the 4q25 site. The 178,808 bp genomic deletion was also found in the lingual tumor. The exact identity of HPV insertional signatures in the two tumors, demonstrates unambiguously that the tongue tumor derived from the anal cancer whereas neither histological immunophenotyping nor classical viral analysis using PCR could allow a definitive diagnosis.ConclusionOur observation indicates that the establishment of a detailed cartography of HPV DNA sequences in a tumor specimen provides crucial information for the design of specific biomarkers that can be used for diagnostic, prognostic or predictive purposes.

Lingual Schwannoma-A Common Tumour at Uncommon Site in a Paediatric Patient: A Case Report and Review of the Literature

Lingual Schwannoma-A Common Tumour at Uncommon Site in a Paediatric Patient: A Case Report and Review of the Literature

Lingual mast cell tumour in a cat

A 12-year-old male neutered domestic shorthair cat was presented for staging and treatment recommendations of a lingual mast cell tumour (MCT). Cytology after fine-needle aspiration of the mandibular lymph nodes...

Analysis of speech and tongue motion in normal and post-glossectomy speaker using cine MRI.

ABSTRACTObjectiveSince the tongue is the oral structure responsible for mastication, pronunciation, and swallowing functions, patients who undergo glossectomy can be affected in various aspects of these functions. The vowel /i/ uses the tongue shape, whereas /u/ uses tongue and lip shapes. The purpose of this study is to investigate the morphological changes of the tongue and the adaptation of pronunciation using cine MRI for speech of patients who undergo glossectomy.Material and MethodsTwenty-three controls (11 males and 12 females) and 13 patients (eight males and five females) volunteered to participate in the experiment. The patients underwent glossectomy surgery for T1 or T2 lateral lingual tumors. The speech tasks “a souk” and “a geese” were spoken by all subjects providing data for the vowels /u/ and /i/. Cine MRI and speech acoustics were recorded and measured to compare the changes in the tongue with vowel acoustics after surgery. 2D measurements were made of the interlip distance, tongue-palate distance, tongue position (anterior-posterior and superior-inferior), tongue height on the left and right sides, and pharynx size. Vowel formants Fl, F2, and F3 were measured.ResultsThe patients had significantly lower F2/Fl ratios (F=5.911, p=0.018), and lower F3/F1 ratios that approached significance. This was seen primarily in the /u/ data. Patients had flatter tongue shapes than controls with a greater effect seen in /u/ than /i/.ConclusionThe patients showed complex adaptation motion in order to preserve the acoustic integrity of the vowels, and the tongue modified cavity size relationships to maintain the value of the formant frequencies.

The origin and role of autophagy in the formation of cytoplasmic granules in canine lingual granular cell tumors.

Granular cell tumors (GCTs) are histologically characterized by polygonal neoplastic cells with abundant eosinophilic cytoplasmic granules. In humans, these cells are considered to be derived from Schwann cells, and the cytoplasmic granules are assumed to be autophagosomes or autophagolysosomes. However, the origin and nature of the cytoplasmic granules in canine GCTs have not been well characterized. The present study examined 9 canine lingual GCTs using immunohistochemistry, transmission electron microscopy (TEM), and cell culture and xenotransplantation experiments. In some cases, the tumor cells expressed S100, CD133, and desmin. The cytoplasmic granules were positive for LC3, p62, NBR1, and ubiquitin. TEM revealed autophagosome-like structures in the cytoplasm of the granule-containing cells. The cultured GCT cells were round to spindle shaped and expressed S100, nestin, Melan-A, CD133, LC3, p62, NBR1, and ubiquitin, suggesting that they were of neural crest origin, redifferentiated into melanocytes, and exhibited upregulated autophagy. The xenotransplanted tumors consisted of spindle to polygonal cells. Only a few cells contained cytoplasmic granules, and some had melanin pigments in their cytoplasm. The xenotransplanted cells expressed S100, nestin, Melan-A, and CD133. P62 and ubiquitin were detected, regardless of the presence or absence of cytoplasmic granules, while LC3 and NBR1 were detected only in the neoplastic cells containing cytoplasmic granules. These findings suggest that some xenotransplanted cells redifferentiated into melanocytes and that autophagy was upregulated in the cytoplasmic granule-containing cells. In conclusion, canine lingual GCTs originate from the neural crest and develop cytoplasmic granules via autophagy. In addition, the microenvironment of GCT cells affects their morphology.

Case report of fetal lingual tumor – perinatal care and neonatal surgical intervention

Fetal tumors are rare and can be difficult to diagnose in utero. In this presentation, we report an infantile hemangiopericytoma of the tongue, and also review the clinical characteristics, imaging appearances, perinatal differential diagnosis, and potential treatments of this tumors. Prenatal diagnosis of lingual fetal tumors with two-dimensional (2D) ultrasound presents a challenge to sonographers and perinatologists because these lesions are rare, usually develop in the third trimester of pregnancy and need a multidisciplinary approach. We describe an lingual tumor and moderate polyhydramnios which were prenatally detected at 31 weeks of gestation with two- dimensional ultrasound. The application of the surface mode of three-dimensional ultrasound improved the visualization of this tumor. Fetal Magnetic resonance imaging was performed to help in prenatal differential diagnostic. The option of prenatal cytology gained by amniocentesis should also be considered. To our knowledge there are no prenatal reports of similar cases. However, in our experience every information provided during the pregnancy, a correct and early diagnose of fetal condition helps to cope with the demands of perinatal management and to explain to the parents and neonatologists the findings of the case.

Results of surgical excision and evaluation of factors associated with survival time in dogs with lingual neoplasia: 97 cases (1995–2008)

To describe the clinical characteristics, treatments, outcomes, and factors associated with survival time in a cohort of dogs with lingual neoplasia that underwent surgical excision. Retrospective case series. Animals-97 client-owned dogs. Medical records of dogs with a lingual tumor examined between 1995 and 2008 were reviewed. Records were included if a lingual tumor was confirmed by histologic examination and surgical excision of the mass was attempted. Data were recorded and analyzed to identify prognostic factors. Clinical signs were mostly related to the oral cavity. For 93 dogs, marginal excision, subtotal glossectomy, and near-total glossectomy were performed in 35 (38%), 55 (59%), and 3 (3%), respectively. Surgery-related complications were rare, but 27 (28%) dogs had tumor recurrence. The most common histopathologic diagnoses for the 97 dogs were squamous cell carcinoma (31 [32%]) and malignant melanoma (29 [30%]). Eighteen (19%) dogs developed metastatic disease, and the overall median survival time was 483 days. Median survival time was 216 days for dogs with squamous cell carcinoma and 241 days for dogs with malignant melanoma. Dogs with lingual tumors ≥ 2 cm in diameter at diagnosis had a significantly shorter survival time than did dogs with tumors < 2 cm. Similar to previous studies, results indicated that lingual tumors are most commonly malignant, and squamous cell carcinoma and malignant melanoma predominate. A thorough physical examination to identify lingual tumors at an early stage and surgical treatment after tumor identification are recommended because tumor size significantly affected survival time.

Carcinoma cuniculatum of the oesophagus and tongue – report of two cases, including TP53 mutational analysis

We present two cases of carcinoma cuniculatum (CC), a very rare, most commonly cutaneous variant of extremely well differentiated squamous cell carcinoma. The tumours were located in the tongue (62-year-old male with enlarging chronic ulcer) and oesophagus (77-year-old male with progressive dysphagia and odynophagia). Both patients were treated surgically (hemiglossectomy and oe-sophagectomy). Histologically, both tumours were composed of deeply invaginating, keratin filled, focally dilated, burrowing channels lined by squamous epithelium which in the lingual tumour was very well differentiated, i.e., with no significant nuclear atypia/pleomorphism. The oesophageal tumour showed intratu-moural dense infiltration of neutrophilic granulocytes with varying degrees of nuclear atypia of the neoplastic squamous epithelium limited to the areas with acute inflammation. These atypical areas did not show any significant nuclear expression of p53 on im-munohistochemistry and no mutation of TP53 was identified after analysis of exons 2 to 11. Both tumours had presented differential diagnostic difficulties on previous biopsies. The patient with oesophageal tumour had no documented recurrence at 1 year and 2 months follow-up. The patient with the lingual tumour was recently diagnosed precluding any meaningful follow-up.

Cytologic, histologic, and immunohistochemical features of lingual liposarcoma in a dog

A 9-year-old female spayed mixed-breed dog was presented to the referring veterinarian with a history of decreased appetite and difficulty with prehension and swallowing because of a firm oval mass in the tongue. On cytologic evaluation of a fine-needle aspirate of the mass there were numerous round to polygonal cells organized individually or in loose clusters with rare branching capillaries. The cells had eosinophilic granular cytoplasm, round to oval nuclei, and occasionally indistinct borders. The cytologic diagnosis was granular cell tumor (GCT) of the tongue. Impression smears of a biopsy sample of the lingual mass contained similar eosinophilic granular cells with variable numbers of clear vacuoles in the background, numerous perivascular arrangements, and occasional lipoblasts, suggestive of liposarcoma. On histologic examination the tumor was composed of numerous lipocytes with rare foci of round eosinophilic granular cells without evidence of vacuolation; occasionally, atypical mitotic figures were seen. Immunohistochemically, the cells were uniformly negative for periodic acid-Schiff and did not express smooth muscle actin, desmin, or cytokeratin but were immunoreactive for vimentin and S100. A diagnosis of well-differentiated liposarcoma was made on the basis of morphologic and immunohistochemical results. Eosinophilic granular cells may be a component of well-differentiated liposarcoma and are not limited to GCT. Liposarcoma should be considered in the differential diagnoses of lingual tumors in the dog when cytological evaluation reveals eosinophilic granular cells consistent with GCT.

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient management strategies. Orthotopic mouse models of oral cancer have been developed to facilitate the study of factors that impact invasion and serve as model system for evaluating anti-tumor therapeutics. In these systems, visualization of disseminated tumor cells within oral cavity tissues has typically been conducted by either conventional histology or with in vivo bioluminescent methods. A primary drawback of these techniques is the inherent inability to accurately visualize and quantify early tumor cell invasion arising from the primary site in three dimensions. Here we describe a protocol that combines an established model for squamous cell carcinoma of the tongue (SCOT) with two-photon imaging to allow multi-vectorial visualization of lingual tumor spread. The OSC-19 head and neck tumor cell line was stably engineered to express the F-actin binding peptide LifeAct fused to the mCherry fluorescent protein (LifeAct-mCherry). Fox1nu/nu mice injected with these cells reliably form tumors that allow the tongue to be visualized by ex-vivo application of two-photon microscopy. This technique allows for the orthotopic visualization of the tumor mass and locally invading cells in excised tongues without disruption of the regional tumor microenvironment. In addition, this system allows for the quantification of tumor cell invasion by calculating distances that invaded cells move from the primary tumor site. Overall this procedure provides an enhanced model system for analyzing factors that contribute to SCOT invasion and therapeutic treatments tailored to prevent local invasion and distant metastatic spread. This method also has the potential to be ultimately combined with other imaging modalities in an in vivo setting.

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient management strategies. Orthotopic mouse models of oral cancer have been developed to facilitate the study of factors that impact invasion and serve as model system for evaluating anti-tumor therapeutics. In these systems, visualization of disseminated tumor cells within oral cavity tissues has typically been conducted by either conventional histology or with in vivo bioluminescent methods. A primary drawback of these techniques is the inherent inability to accurately visualize and quantify early tumor cell invasion arising from the primary site in three dimensions. Here we describe a protocol that combines an established model for squamous cell carcinoma of the tongue (SCOT) with two-photon imaging to allow multi-vectorial visualization of lingual tumor spread. The OSC-19 head and neck tumor cell line was stably engineered to express the F-actin binding peptide LifeAct fused to the mCherry fluorescent protein (LifeAct-mCherry). Fox1nu/nu mice injected with these cells reliably form tumors that allow the tongue to be visualized by ex-vivo application of two-photon microscopy. This technique allows for the orthotopic visualization of the tumor mass and locally invading cells in excised tongues without disruption of the regional tumor microenvironment. In addition, this system allows for the quantification of tumor cell invasion by calculating distances that invaded cells move from the primary tumor site. Overall this procedure provides an enhanced model system for analyzing factors that contribute to SCOT invasion and therapeutic treatments tailored to prevent local invasion and distant metastatic spread. This method also has the potential to be ultimately combined with other imaging modalities in an in vivo setting.

Hypertrophy and neuron loss: structural changes in sheep SCG induced by unilateral sympathectomy

Recently, superior cervical ganglionectomy has been performed to investigate a variety of scientific topics from regulation of intraocular pressure to suppression of lingual tumour growth. Despite these recent advances in our understanding of the functional mechanisms underlying superior cervical ganglion (SCG) growth and development after surgical ablation, there still exists a need for information concerning the quantitative nature of the relationships between the removed SCG and its remaining contralateral ganglion and between the remaining SCG and its modified innervation territory. To this end, using design-based stereological methods, we have investigated the structural changes induced by unilateral ganglionectomy in sheep at three distinct timepoints (2, 7 and 12 weeks) after surgery. The effects of time, and lateral (left-right) differences, were examined by two-way analyses of variance and paired t-tests. Following removal of the left SCG, the main findings were: (i) the remaining right SCG was bigger at shorter survival times, i.e. 74% at 2 weeks, 55% at 7 weeks and no increase by 12 weeks, (ii) by 7 weeks after surgery, the right SCG contained fewer neurons (no decrease at 2 weeks, 6% fewer by 7 weeks and 17% fewer by 12 weeks) and (iii) by 7 weeks, right SCG neurons were also larger and the magnitude of this increase grew substantially with time (no rise at 2 weeks, 77% by 7 weeks and 215% by 12 weeks). Interaction effects between time and ganglionectomy-induced changes were significant for SCG volume and mean perikaryal volume. These findings show that unilateral superior cervical ganglionectomy has profound effects on the contralateral ganglion. For future investigations, it would be interesting to examine the interaction between SCGs and their innervation targets after ganglionectomy. Is the ganglionectomy-induced imbalance between the sizes of innervation territories the milieu in which morphoquantitative changes, particularly changes in perikaryal volume and neuron number, occur? Mechanistically, how would those changes arise? Are there any grounds for believing in a ganglionectomy-triggered SCG cross-innervation and neuroplasticity?

Abstract B62: Zinc supplementation reduces forestomach tumor burden in N-nitrosomethylbenzylamine-treated mice

Abstract Zinc deficiency is associated with high incidences of esophageal and other human cancers. In addition, zinc status in plasma and white blood cells is a better indicator of tumor burden and stage of the disease in head and neck cancer patients than overall nutritional status. Research in rodents found that zinc insufficiency leads to a highly proliferative hyperplastic condition in the upper gastrointestinal tract. Zn replenishment reduces the incidence of lingual, esophageal, and forestomach tumors in Zn-deficient rats and mice. While previous animal studies focused on the effect of Zn deficiency on cancer prevention and development, in this study we investigated the effect of Zn supplementation on carcinogenesis in Zn-sufficient mice of wild type and three tumor suppressor-deficient mouse strains, Fhit−/−, Fhit−/−Nit1−/−, and Fhit−/−Rassf1a−/−. About fifty mice from each strain received 6-8 doses of N-nitrosomethylbenzylamine (NMBA). Half the mice then received Zn supplemented water while another half received regular water. Sixteen weeks after last NMBA administration, mice were sacrificed and tumors were found only in forestomach. Mice without Zn supplementation had developed more tumors than Zn-supplemented mice: wild type C57BL/6 mice developed an average of 7.0 vs 5.0 tumors for Zn supplemented (p&amp;lt;0.05); Zn-supplemented Fhit−/− mice averaged 5.7 vs 8.0 for control mice (p&amp;lt; 0.01); Zn-supplemented Fhit−/−Nit1−/− mice averaged 5.4 vs 9.2 for control mice (p&amp;lt; 0.01); and Zn-supplemented Fhit−/−Rassf1a−/−mice averaged 5.9 vs 9.1 for control mice (p&amp;lt; 0.01). Zn supplementation reduced tumor burdens by 28% (wild type) to 42% (Fhit−/−Nit1−/−). Histological analysis of forestomach tissues also showed significant decreases in severity of preneoplastic and neoplastic lesions in Zn-supplemented cohorts of each mouse strain. Thus, Zn supplementation significantly reduced tumor burdens in mice with multiple tumor suppressor deficiencies. When Zn supplementation was begun at 7 weeks after the final carcinogen dose, the reduction in tumor burden was the same as observed when supplementation began immediately after carcinogen dosing, suggesting that Zn supplementation may affect tumor progression rather than tumor initiation. Our study suggests that Zn could have an important role in tumor prevention and perhaps treatment of specific human cancers and should be more thoroughly studied in preclinical models. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B62.

Primary sebaceous carcinoma of the tongue

Sebaceous carcinoma is the rarest type of oral malignancies. We report a case of primary sebaceous carcinoma of the tongue. Systemic imaging studies revealed that the patient had a T2N2cM0 (International Union Against Cancer guidelines) primary lingual tumor. Histopathological examination revealed neoplastic sebocytic and basaloid cells, and Sudan III staining and electron microscopy revealed intracytoplasmic lipid droplets. The neoplastic cells stained positive for adipophilin; epithelial membrane antigen; epithelial antigen; and cytokeratins 7, 8, and 15, but negative for cytokeratins 5/6, 18, 19, and 20; the androgen receptor; and carcinoembryonic antigen. Superselective intraarterial chemotherapy was administered via the superficial temporal artery concurrent with daily radiotherapy. Multiple biopsies confirmed a complete response of the primary lesion. The patient then underwent neck dissection followed by pathological examination, which revealed lymph nodes metastases. After postoperative radiotherapy to the neck, distant metastases were identified in the mediastinal lymph nodes and the lung. The patient died 17 months after completing the initial course of chemoradiotherapy. Our case demonstrates that superselective intraarterial chemotherapy combined with concurrent radiotherapy can be effective in treating the primary lesion of patients with a sebaceous carcinoma of the tongue. However, an effective strategy to eradicate metastases has yet to be established.

Effect of zinc supplementation on N-nitrosomethylbenzylamine-induced forestomach tumor development and progression in tumor suppressor-deficient mouse strains

Zinc deficiency is associated with high incidences of esophageal and other cancers in humans and leads to a highly proliferative hyperplastic condition in the upper gastrointestinal tract in laboratory rodents. Zn replenishment reduces the incidence of lingual, esophageal and forestomach tumors in Zn-deficient rats and mice. While previous animal studies focused on Zn deficiency, we have investigated the effect of Zn supplementation on carcinogenesis in Zn-sufficient mice of wild-type and tumor suppressor-deficient mouse strains. All mice received N-nitrosomethylbenzylamine and half the mice of each strain then received Zn supplementation. At killing, mice without Zn supplementation had developed more tumors than Zn-supplemented mice: wild-type C57BL/6 mice developed an average of 7.0 versus 5.0 tumors for Zn supplemented (P < 0.05); Zn-supplemented Fhit-/- mice averaged 5.7 versus 8.0 for control mice (P < 0.01); Zn-supplemented Fhit-/-Nit1-/- mice averaged 5.4 versus 9.2 for control mice (P < 0.01) and Zn-supplemented Fhit-/-Rassf1a-/- (the murine gene) mice averaged 5.9 versus 9.1 for control mice (P < 0.01). Zn supplementation reduced tumor burdens by 28% (wild-type) to 42% (Fhit-/-Nit1-/-). Histological analysis of forestomach tissues also showed significant decreases in severity of preneoplastic and neoplastic lesions in Zn-supplemented cohorts of each mouse strain. Thus, Zn supplementation significantly reduced tumor burdens in mice with multiple tumor suppressor deficiencies. When Zn supplementation was begun at 7 weeks after the final carcinogen dose, the reduction in tumor burden was the same as observed when supplementation began immediately after carcinogen dosing, suggesting that Zn supplementation may affect tumor progression rather than tumor initiation.