Atypical Location of Oral Metastasis as the First Manifestation of Renal Carcinoma. Case Report / Localización Atípica de Metastasis Oral como Primera Manifestación de Carcinoma Renal. Reporte de Caso

Oral cavity metastatic tumors derived from primary tumors from other corporal regions are rare, representing barely 1 % of all malignant tumors. Differential diagnosis of these lesions is challenging due to the wide spectrum of lesions with similar clinical presentation and especially when the presence of a primary tumor goes undetected. We present the case of a 55-year-old male with a painless tumor in the anterior maxillary region, vestibular gingiva and palate, with a 2-month evolution. Anatomopathological diagnosis was malignant clear cell tumor, highly suggestive of clear cell renal carcinoma metastasis, and the oral lesion constituted the first sign of illness.

Los tumores metastásicos de cavidad oral derivados de tumores primarios de otras regiones corporales son raros, representando apenas el 1 % de todos los tumores malignos. El diagnóstico diferencial de estas lesiones es desafiante debido al amplio espectro de lesiones con presentación clínica similar y especialmente cuando la presencia de un tumor primario pasa desapercibida. Presentamos el caso de un varón de 55 años con una tumoración indolora en región maxilar anterior, encía vestibular y paladar, de 2 meses de evolución. El diagnóstico anatomopatológico fue de tumor maligno de células claras, altamente sugestivo de metástasis de carcinoma renal de células claras, y la lesión bucal constituyó el primer signo de enfermedad.

Differential Diagnosis of Oral Metastases / Diagnóstico Diferencial de las Metástasis Orales

Metastatic lesions in the mouth can resemble common inflammatory lesions. Therefore, we set out to investigate oral metastases whose clinical and imaging characteristics mimicked those of harmless lesions, confusing and delaying the diagnosis. For this, a systematic review was carried out from case reports, case series, and cross-sectional studies in the PubMed/Medline, Scopus, Embase-via Elsevier, Virtual Health Library, Web of Science, and gray literature, using PICO strategy without period restriction. We assessed the quality of studies using the Joanna Briggs Institute assessment tool. A narrative synthesis of the data was carried out. Association analyses using chi-square and Fisher's exact tests were performed, with statistical significance at p<0.05. Most of the lesions came from the lung, breast, kidneys, liver, and thyroid. They affected mainly the mandibles of men, between the fifth and seventh decades of life, causing osteolysis. In soft tissue, there were firm swellings, associated with bleeding. Limitations regarding the heterogeneity of the included studies and the absence of clinic pathological descriptions of the tumors substantially reduced the chance of statistical analysis of the data. Knowing the different possibilities of clinical presentation of oral and maxillofacial metastases is important for the diagnost ic suspicion to occur and diagnostic errors to be avoided. Thus, treatment is instituted and survival can be extended. Protocol registration: PROSPERO CRD42020200696.

Las lesiones metastásicas en la cavidad oral pueden parecer similares a lesiones inflamatorias comunes. Por ello, nos propusimos investigar metástasis orales cuyas características clínicas e imagenológicas simularan las de lesiones inofensivas, confundiendo y retrasando el diagnóstico. Para ello, se realizó una revisión sistemática a partir de reportes de casos, series de casos y estudios transversales en PubMed/Medline, Scopus, Embase-vía Elsevier, Virtual Health Library, Web of Science y literatura gris, utilizando la estrategia PICO sin restricción de periodo. La calidad de los estudios se evaluó mediante la herramienta de evaluación del Instituto Joanna Briggs. Se realizó una síntesis narrativa de los datos. Se realizaron análisis de asociación mediante chi-cuadrado y prueba exacta de Fisher, con significancia estadística en p<0,05. La mayoría de las lesiones procedían de pulmón, mama, riñones, hígado y tiroides. Afectan principalmente a las mandíbulas de los hombres, entre la quinta y la séptima década de la vida, provocando osteólisis. En los tejidos blandos, había hinchazones firmes, asociadas con sangrado. Las limitaciones con respecto a la heterogeneidad de los estudios incluidos y la ausencia de descripciones clinicopatológicas de los tumores redujeron sustancialmente la posibilidad de realizar un análisis estadístico de los datos. Conocer las diferentes posibilidades de presentación clínica de las metástasis orales y maxilofaciales es importante para que se produzca la sospecha diagnóstica y se eviten errores diagnósticos. Por lo tanto, se instituye el tratamiento y se puede prolongar la supervivencia. Registro de protocolo: PROSPERO CRD42020200696.

Metastasis to the oral and maxillofacial region. A systematic review.

OBJECTIVE: Metastasis to oral and maxillofacial region (MOMFR) is an unusual finding; representing between 1 and 1.5% of all malignancies in the maxillofacial region. A systematic review is presented to determine trends in presentation, diagnostic features, and patient outcome. METHODS: Searches of databases were carried out for papers reporting MOMFR. The variables were demographics, patient symptoms, tumor location, tumor size, histopathology, origin of the tumor, immunohistochemical studies, follow-up and survival. RESULTS: 696 cases were identified; 391 males, and 305 females. The most common race was white. The most common primary tumor for females was from breast 31.1% (n = 95), for males from lung 20.5% (n = 143). The most common location was the mandible 44.9% (n = 313), followed by gingival soft tissue 16.8% (n = 117). A frequent clinical symptom was pain with 17.5% (n = 122). The most common clinical presentation was a mass or tumor 37.4% (n = 260). The mean age was 58.8 years. The average time before diagnosis was 10.3 months, the mean follow-up after diagnosis was 13.1 months, and the average survival was 9.8 months. CONCLUSION: MOMFR shows a strong predilection for the posterior mandible, with a mass or tumor being the most common clinical presentation. They are frequently painful, and demonstrate a poor prognosis.

Metástasis oral de carcinoma de células renales. A propósito de un caso y revisión de la literatura / Oral metastasis of renal cell carcinoma. A Case report and literature review / Metástase oral de carcinoma de células renais. Relato de um caso e revisão da literatura

Los tumores metastásicos en cavidad oral son pocos frecuentes, representan el 1% de las neoplasias malignas orales, son relativamente más frecuentes en los maxilares, respecto a aquellos localizados en los tejidos blandos orales. Se describe el caso de una paciente de 75 años de edad, con antecedentes de carcinoma renal de células claras, que consulta por la aparición repentina de una lesión tumoral en reborde alveolar superior izquierdo. Se realizó la biopsia exéresis con diagnóstico presuntivo de tumor metastásico o posible lesión reactiva. El informe anátomo - patológico confirma el diagnóstico de metástasis de un carcinoma renal. Las metástasis orales tienen un pronóstico generalmente malo, compromete la sobrevida, por lo que es importante realizar un exhaustivo estudio del paciente y considerar sus antecedentes, ya que en ocasiones son diagnosticadas tardíamentete.

Metastatic tumors to the oral cavity are rare, representing only 1% of malignant oral neoplasms. These metastatic tumors occur more frequently in the jaws than in soft oral tissues. This article describes the case of a 75-year-old patient with a history of clear cell renal carcinoma who seeks care because of the sudden appearance of a tumor lesion in the upper left alveolar ridge. An excision biopsy was performed with a presumptive diagnosis of a metastatic tumor or potential reactive lesion. The pathology report confirmed the diagnosis of renal cell carcinoma metastasis. Oral metastatic tumors usually present a bad prognosis with a low survival rate. It is important to examine patients thoroughly and consider their medical records, as they are sometimes diagnosed late.

Os tumores metastásicos na cavidade oral são raros, representam 1% das neoplasias malignas orais, sendo relativamente mais frequentes nos ossos maxilares enquanto aos localizados nos tecidos moles orais. Descreve-se o caso de uma mulher de 75 anos com história de carcinoma renal de células claras, que consultou com queixa de lesão tumoral localizada na crista alveolar superior esquerda. Uma biópsia foi feita com diagnóstico clínico presuntivo de tumor metastático ou possível lesão reativa. O laudo anátomopatológico confirmou o diagnóstico de metástase de carcinoma renal. As metástases orais geralmente têm um prognóstico ruim, com baixa sobrevivência, portanto é importante fazer um estudo exaustivo do paciente e tomar em conta sua história, já que às vezes o diagnóstico é tardio.

Worst pattern of invasion - type 4 (WPOI-4) and Lymphocyte host response should be mandatory reporting criteria for oral cavity squamous cell carcinoma: A re-look at the American Joint Committee of Cancer (AJCC) minimum dataset.

BACKGROUND: A proportion of early-stage node-negative oral squamous carcinoma patients fail despite complete surgical resection. Adjuvant treatment in early oral cancer is controversial and is often individualized based on stage, depth, and margin status. AIMS: We reviewed various histological markers in pT1/T2N0 cases, resected upfront with elective nodal dissection, with an emphasis on tumor-tissue interface characteristics of the worst pattern of invasion (WPOI), tumor cell nest size (sCNS), budding and lymphocytic host response (LHR), to assess their prognostic significance. MATERIALS AND METHODS: Archived blocks of 95 cases were reviewed. Tumor stage, grade, size, depth of invasion, lymphovascular, and perineural invasion, WPOI, LHR, sCNS, and tumor bud (single cells or <5 cell clusters) score were recorded. STATISTICAL ANALYSIS: Prognostic significance was statistically analyzed using SPSS software version 20. RESULTS: Depth of invasion (P = 0.008), WPOI- 4 and 5 (P = 0.033), sCNS (<5 cells) at tumor interface (P = 0.010), high bud count (≥3 buds/40 × hpf) (P = 0.021) and poor LHR (P = 0.019) correlated significantly with poor disease-free survival on univariate analysis. However, on multivariate analysis only LHR and WPOI-4 (that is presence of small cell nests or buds) were significant, with high hazard ratio of 4.351 (95% CI 1.290-14.676, P = 0.018) and 5.019 (95% CI 1.212-20.789, P = 0.026), respectively. CONCLUSION: We propose mandatory reporting of WPOI-4 at the tumor interface and absence of LHR, as significant markers of poor prognosis in early-stage oral cavity squamous carcinoma.

Metastatic tumors in oral mucosa and jawbones: Unusual primary origins and unusual oral locations.

AIM: To perform clinico-pathological characterization of a large series of oral metastases, collected from 3 main medical centers in Israel and compare findings to data on frequency of primary cancer types in the population. MATERIALS: Pathology archives were searched for cases of metastatic tumors to the oral soft tissues and jawbones, 1990 - 2016. Metastases to the skin of face or to major salivary glands have been excluded. Demographic data and histopathological features were analyzed. RESULTS: Study population included 60 patients, 35 females and 25 males (ratio of 1.4:1). The age range was 17-87 years, mean 67.7 + 14.36 years. Only 3 (5%) patients were under 40 years, the remaining clustered predominantly in the 60-80 year age group. The mean age of females (59 + 13.84) was significantly lower than that of males (67.44 + 14) (p = 0.03). There was an almost equal distribution between the oral soft tissue and the jawbones (48.3% and 51.7%, respectively). The five most common organs from which metastases were distributed to the oral cavity and jawbones combined were kidney (20%), breast (15%), cutaneous (predominately melanoma, 13%), lung (11.7%) and soft tissue-sarcomas (8.3%). For comparison, Israel National Cancer Registry 2013 reported that the most frequent malignancies were breast (25.8%), colorectal cancer (16.3%), lung (12%) and prostate (10%). Malignant melanoma was 6th (5.4%), kidney malignancy was only 9th in frequency (4.2%). Although the gingiva and jawbones were the most frequent locations, some cases presented in unusual locations, (mandibular vestibule, lower lip, posterior dorsal tongue), without any specific clinical feature to suggest metastasis. CONCLUSIONS: The most frequent primary origins for oral metastasis do not correspond to the relative frequency of the primary tumors in the population, indicating that metastatic spread is not a random process. Although the majority of metastasis involves the gingiva and jawbones, any other oral mucosal location might be involved. Thus, in adult/older patients, metastasis from a distant site should be included in the differential diagnosis of oral masses at any oral location, whether the existence of a primary tumor is reported or not.

Fatal case of oral metastatic hepatocellular carcinoma in a patient unaware of his disease.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Metastases to the soft tissues of the oral cavity are extremely uncommon. This report describes a rare case of an oral metastatic HCC, located completely within the oral mucosa overlying the alveolar ridge, in a patient who was unware of his primary disease. A 64-year-old man was referred for evaluation of a nodular mass on the edentulous mandibular ridge underneath an implant-supported overdenture. According to the patient, he was successfully treated for hepatitis C infection 7 years previously, and he reported that his α-fetoprotein levels were monitored at semiannual intervals. The results of his current blood tests were within the reference range. A biopsy was performed, and analysis of the specimen revealed a malignant neoplasm suggestive of metastatic HCC. Because the patient was unaware of any underlying disease, he was referred to an oncologist for further evaluation. However, signs of hepatic decompensation appeared immediately after the biopsy results were obtained, and the patient was hospitalized. The overall medical examination disclosed an HCC with metastases to the lungs and oral cavity, and the patient died 8 days after hospitalization. This case reinforces the important potential for dentists to identify neoplastic diseases that are unknown to their patients.

Oral and maxillofacial metastasis of male breast cancer: Report of a rare case and literature review.

Oral and maxillofacial metastatic tumors are uncommon, with the breast, prostate, lung, and kidney representing the most common primary sites. Less than 1% of all breast cancers occur in male patients, and to date, only 8 cases of metastatic breast adenocarcinoma to the oral and maxillofacial region in a male patient have been reported in the literature. An 88-year-old male with previous history of a successfully treated primary breast adenocarcinoma 12 years earlier was referred for evaluation of an oral swelling lasting 6 months. Intraoral examination revealed a 2-cm reddish, pedunculated nodule with a smooth surface located in the left retromolar region. Imaging revealed maxillary sinus involvement. The patient underwent incisional biopsy, and microscopic evaluation revealed invasive tumor islands compounded by malignant epithelial cells, sometimes exhibiting ductal arrangement, which were positive for the estrogen receptor and gross cystic disease fluid protein 15. The final diagnosis was metastatic breast adenocarcinoma. Breast metastases are exceedingly rare in the oral and maxillofacial region of male patients; however, clinicians should consider breast metastasis when evaluating reddish oral nodules in older patients, including men, especially those with a history of malignancy.

A challenging diagnosis: Case report of oral metastasis from gastric adenocarcinoma mimicking pyogenic granuloma.

RATIONALE: Oral metastases occur more commonly in bone, but can also manifest in soft tissues and eventually resemble a reactive lesion. Few cases of oral metastases mimicking reactive lesions in soft tissues have been reported to date. PATIENT CONCERNS: We report a metastasis of gastric carcinoma (GC) to the oral mucosa without bone involvement in a 43 yom clinically and microscopically mimicking a reactive lesion. The patient related that the lesion had 1 month of evolution, and the ulcerated area suggested the lesion was related to trauma. DIAGNOSES: The histopathological examination of the lesion revealed an exuberant granulation tissue with few neoplastic cells, and the initial diagnosis of pyogenic granuloma was considered. In a second analysis, clusters of clear cells morphologically similar to degenerating mucous cells or macrophages, positive for Cytokeratin (CK)-20, and CDX2 were found. At the moment, it was confirmed the presence of a primary GC in the patient. INTERVENTIONS: A palliative radiotherapy/chemotherapy was started. OUTCOMES: However, the patient died 3 months after the diagnosis of oral metastasis. LESSONS: This report highlights the importance of careful clinical and microscopic examinations in cases of oral metastasis that may mimic a reactive lesion.

Cytologic Features of Malignant Melanoma with Osteoclast-Like Giant Cells.

BACKGROUND: Malignant melanoma showing numerous osteoclast-like giant cells (OGCs) is an uncommon morphologic phenomenon, rarely mentioned in the cytologic literature. The few reported cases seem to have an aggressive clinical behavior. Although most findings support monocyte/macrophage differentiation, the exact nature of OGCs is not clear. CASE: A 57-year-old woman presented with an inguinal lymphadenopathy. Sixteen years before, cutaneous malignant melanoma of the lower limb had been excised. Needle aspiration revealed abundant neoplastic single cells as well as numerous multinucleated OGCs. Occasional neoplastic giant cells were also present. Nuclei of OGCs were monomorphic with oval morphology and were smaller than those of melanoma cells. The immunophenotype of OGCs (S100-, HMB45-, Melan-A-, SOX10-, Ki67-, CD163-, BRAF-, CD68+, MiTF+, p16+) was the expected for reactive OGCs of monocyte/macrophage origin. The tumor has shown an aggressive behavior with further metastases to the axillary lymph nodes and oral cavity. CONCLUSION: Numerous OGCs are a rare and relevant finding in malignant melanoma. Their presence should not induce confusion with other tumors rich in osteoclastic cells. Since a relevant number of OGCs in melanoma may mean a more aggressive behavior, and patients may benefit from specific treatments, their presence should be mentioned in the pathologic report.

Analytic survey of 57 cases of oral metastases.

BACKGROUND: Oral lesions have been reported among the first signs of an undiagnosed metastatic disease. Accurate diagnosis of an occult metastasis remains critical in determining the treatment course. Previous studies regarding oral metastatic tumors present varied data regarding the most frequent metastases to the oral cavity. These discrepancies echo the changes in incidence rates for certain malignancies over time and demonstrate the need for periodic updates in oral metastasis studies. METHODS: Using Text Information Extraction System, a de-identified pathology database, we compiled 57 cases over a period of 19 years using key terms to search for oral metastases. RESULTS: For both males and females, the most common primary sites were lung (21.1%), liver (12.3%), breast (10.5%), kidney (10.5%), and colorectal (8.8%). We found an equal number of lung and breast metastases in females and metastases from the liver to be the most prevalent for males. In most of our cases (54.9%), the patient had no history of the primary malignancy and the oral lesion preceded awareness of the widespread cancer. CONCLUSIONS: As a departure from many previous case series, we found lung and breast metastases to be equally numerous in women and liver as the most common oral metastasis in men. Also, we identified a tendency for the patient to present with a previous history in certain malignancies, such as breast cancer, whereas in other malignancies, such as renal cell carcinoma, our data demonstrated a propensity to present in the oral cavity without history of a primary tumor.

[Renal Cell Carcinoma metastases in the maxillofacial area: Case series.] / Metástasis en región maxilofacial de carcinoma renal: serie de casos.

Renal cell carcinoma is an unpredictable malignancy. Sometimes, metastases are the disease debut. On the other hand, metastases could present years after treatment of the primary tumor. Four clinical cases of atypical metastases in the head and neck location are presented: parotid gland, mandibular bone, attached molar gingiva and masticator space. Physiopathology, clinics, histology and management of metastatic renal cell carcinoma at those anatomical regions are reviewed.

Metástasis en región maxilofacial de carcinoma renal: serie de casos / Renal Cell Carcinoma metastases in the maxillofacial area: Case series

El carcinoma renal es un tumor de evolución imprevisible. A veces las metástasis son el debut de la enfermedad, mientras que en otras, éstas se manifiestan años tras el tratamiento del primario. Se presentan 4 casos clínicos de metástasis atípicas de carcinoma renal en región de cabeza y cuello: glándula parótida, hueso mandibular, encía adherida molar y espacio masticador. Se revisa la fisiopatología, clínica, histología y manejo del cáncer renal metastásico en esas localizaciones

Renal cell carcinoma is an unpredictable malignancy. Sometimes, metastases are the disease debut. On the other hand, metastases could present years after treatment of the primary tumor. Four clinical cases of atypical metastases in the head and neck location are presented: parotid gland, mandibular bone, attached molar gingiva and masticator space. Physiopathology, clinics, histology and management of metastatic renal cell carcinoma at those anatomical regions are reviewed

Metastasis of a Renal Collecting Duct Adenocarcinoma to the Oral Cavity After Tooth Extraction.

Metastatic tumors rarely occur in the oral cavity. The most common of the oral metastases are lung cancers in males, and breast and genital cancers in females. The most common primary tumor metastasis to the oral cavity is from the lung, kidney, liver, prostate, and colorectal cancers. The metastatic lesions are similar to oral lesions such as pyogenic granuloma, giant cell lesions, gingival polyps, hemangioma, peripheral fibroma, and adenoid squamous cell carcinoma. Therefore, the diagnosis of primary tumors is challenging. To our knowledge, this is the first reported case to feature metastasis of a renal collecting duct adenocarcinoma to the oral cavity after tooth extraction.

Metastatic carcinoma of the oral region: An analysis of 21 cases

BACKGROUND: Metastatic carcinoma to the jaws and oral region are very rare, representing less than 1% of all oral tumors. Unfortunately, oral metastasis is usually manifestation of an advanced stage of primary cancer, and indicates widespread disease and poor prognosis. MATERIAL AND METHODS: In this retrospective study, a total of 2039 patients with history of oral malignant tumor between 1980 and 2012 at Seoul National University Dental Hospital were evaluated. We analyzed the dental and medical records, and histopathological database of 2039 patients to assess the prevalence of oral metastasis of carcinoma in terms of sex and age, as well as, the most common origin of primary cancer, and prevalent site and histopathological type of metastatic carcinoma. RESULTS: Among 2039 patients, 21 (1.03%) were finally diagnosed with metastatic carcinoma of the jaws and oral region. Among the 21 patients, only 11 had a working diagnosis as oral metastasis upon clinical evaluation before performing a biopsy. The mean age at the time of diagnosis with a metastatic carcinoma was 56.86, and there was a male preponderance. Metastatic carcinoma was more frequent in the jaws than in the soft tissue, especially in the mandible compared to the maxilla. The most frequent primary site was the lungs, followed by the liver and breasts. The predominant histopathological types were hepatocellular carcinoma and adenocarcinoma. Patient outcomes indicated a poor prognosis with the time from the appearance of the metastasis to death was only 12 months. CONCLUSIONS: According to these cases, oral metastases of carcinoma were exceedingly rare in Koreans. It can allow the clinicians take into account the possible presence of metastases and lead to early diagnosis

Metastatic carcinoma of the oral region: An analysis of 21 cases.

BACKGROUND: Metastatic carcinoma to the jaws and oral region are very rare, representing less than 1% of all oral tumors. Unfortunately, oral metastasis is usually manifestation of an advanced stage of primary cancer, and indicates widespread disease and poor prognosis. MATERIAL AND METHODS: In this retrospective study, a total of 2039 patients with history of oral malignant tumor between 1980 and 2012 at Seoul National University Dental Hospital were evaluated. We analyzed the dental and medical records, and histopathological database of 2039 patients to assess the prevalence of oral metastasis of carcinoma in terms of sex and age, as well as, the most common origin of primary cancer, and prevalent site and histopathological type of metastatic carcinoma. RESULTS: Among 2039 patients, 21 (1.03%) were finally diagnosed with metastatic carcinoma of the jaws and oral region. Among the 21 patients, only 11 had a working diagnosis as oral metastasis upon clinical evaluation before performing a biopsy. The mean age at the time of diagnosis with a metastatic carcinoma was 56.86, and there was a male preponderance. Metastatic carcinoma was more frequent in the jaws than in the soft tissue, especially in the mandible compared to the maxilla. The most frequent primary site was the lungs, followed by the liver and breasts. The predominant histopathological types were hepatocellular carcinoma and adenocarcinoma. Patient outcomes indicated a poor prognosis with the time from the appearance of the metastasis to death was only 12 months. CONCLUSIONS: According to these cases, oral metastases of carcinoma were exceedingly rare in Koreans. It can allow the clinicians take into account the possible presence of metastases and lead to early diagnosis.