Bioradiotherapy with Cetuximab May Reduce the Risk of Neck Node Relapse in Locoregionally Advanced Laryngeal Glottic Carcinoma: May HER1-Profile Be Useful in the Bioselection of Patients?

The aim of the study was to evaluate survival in patients with advanced glottic laryngeal squamous cell carcinoma treated by bioradiotherapy (BioRT) with cetuximab and eventual salvage surgery (group A, n = 66) or upfront surgery (total laryngectomy or near-total laryngectomy) with or without postoperative radiotherapy (PORT) (group B, n = 66). The predictive role of HER1 expression in the bioselection of tumors was evaluated. Relapse-free (RFS), metastasis-free (MFS), overall (OS) survivals, salvageability, and rates of larynx preservation were analyzed. The two groups were balanced by propensity score method on their baseline characteristics. No significant differences in RFS and OS were found, while MFS results were significantly higher in group A (p = 0.04). Group A showed a 22% reduction in the probability of nodal metastasis (p = 0.0023), mostly in tumors with higher HER1 expression. The salvageability with TL at 3 years was 54% after prior BioRT and 18% after prior upfront NTL (p < 0.05). BioRT with cetuximab showed a reduction in the risk of lymph node relapse, particularly in the case of HER1 positive tumors, and it allowed to achieve a higher rate of functional larynx preservation and a higher salvageability compared with upfront surgery. HER1 analysis could be clinically useful in the bioselection of tumors that may benefit from BioRT with cetuximab, particularly in those with neck node metastatic propensity.

Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 in locally advanced laryngeal cancer as prognostic indicators of relapse and survival.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients. METHODS: We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab. RESULTS: The expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62-22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19-105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04-0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04-0.91; p = 0.029). CONCLUSIONS: In LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.

Thymic carcinomas and thymic neuroendocrine tumors: a tribute to Dr. Juan Rosai.

Throughout his career, Dr. Juan Rosai greatly impacted our understanding of mediastinal tumors, both as a scientist and as a teacher. This review highlights his manifold contributions in the field of thymic carcinomas and thymic neuroendocrine tumors from a historical perspective.

Juan Rosai as master of our comprehensive understanding of thymus and thymoma.

In this study, the authors report on the activity of Juan Rosai, one of the pathologists most engaged in the definition of cells, diseases and tumors occurring in the thymus and in the mediastinum during the last 60 years. With his morphological skills and tireless interest in clarification of disease patterns, he contributed extraordinarily to expand our knowledge of the mediastinal diseases and to improve our diagnostic approach. He determined extraordinary advances also in trasmission electron microscopy and in immunohistochemistry as powerful diagnostic tools. Moreover, he proposed and promoted, together with an international panel of Pathologists, the World Health Classification of Thymic tumors as a definite progress in our comprehension and diagnostics of thymic epithelial tumors (TET). Our purpose is to review J. Rosai's achievements in thymic normal structure, in TET and particularly in the entity now definied as "thymoma", in distinction from the thymic carcinoma. To do this, our narrative will also be based on personal memories, longstanding collaborations and/or friendship with J. Rosai.

Nuclear HER3 expression improves the prognostic stratification of patients with HER1 positive advanced laryngeal squamous cell carcinoma.

BACKGROUND: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear. METHODS: We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan-Meier and Cox's proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination. RESULTS: Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively. CONCLUSIONS: Nuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma.

Neuroimages and Neuropathology of a Stroke-Like Cerebral Lymphomatoid Granulomatosis.

A 70-year-old man presented to the Emergency Department reporting the acute onset of non-fluent aphasia, hyposthenia, and hemi-anesthesia of the right body. Brain computerized tomography revealed a subcortical hypodense lesion in the middle cerebral artery territory. Neck ultrasounds of internal and external carotid arteries and of the vertebral arteries showed a focal moderate stenosis of the left internal carotid artery due to a soft atheromasic plaque. These findings that were initially consistent with a diagnosis of an ischemic stroke were not confirmed by magnetic resonance (MR). The latter showed an hyperintense lesion on FLAIR and T2-weighted sequences located in the left centrum semiovale, corona radiata, and thalamus, with a well-defined regular rim and a mild compressive effect on the lateral ventricle, with diffusivity restriction but without ADC reduction and with a punctate and serpiginous gadolinium enhancement on T1 sequences (Figure 1). Within the first day of observation, the patient started complaining progressive mental deterioration, in absence of any other possible causes, and a total body CT scan excluded any other organ involvement. Patient was then referred to the neurosurgeon in order to perform a brain biopsy. The neuropathology was compatible with the diagnosis of cerebral lymphomatoid granulomatosis (LG) (Figure 1).

Primary cardiac synovial sarcoma: A review correlating outcomes with surgery and adjuvant therapy.

BACKGROUND: Cardiac synovial sarcoma (CSS) is an extremely rare malignant tumor with a severe prognosis, due to frequent relapses and metastases. To obtain useful information for treatment protocols, we analyzed survival and therapy data from the cases reported in the literature. METHODS: A search of MEDLINE was performed throughout December 2018. Using key words relating to primary CSS, we collected from the literature a total of 97 cases, mainly consisting of single case reports. To identify predictors of overall survival, statistical analyses were performed on a selected cohort of 55 patients for whom relevant clinicopathological data were available, including surgery and adjuvant therapy. RESULTS: The univariable analysis revealed that patients in their first three decades of life have better overall survival. The univariable analysis also showed that patients not receiving adjuvant chemotherapy are at increased risk of death. In the multivariable analysis, tumor resection and chemotherapy are factors significantly improving overall survival. CONCLUSION: The survival of patients with CSS is positively influenced by a young patient's age and greatly improved by the administration of chemotherapy, even in the absence of tumor resection.

Intracranial neuromuscular choristoma: Report of a case with literature review.

Neuromuscular choristoma (NMC), also called neuromuscular hamartoma or nerve rhabdomyoma, is a rare lesion of the spinal and cranial nerves composed of skeletal muscle intimately associated with nerve fibers. Its origin has not been precisely clarified and a malformative event, resulting from aberrant differentiation or a true neoplastic growth, have been proposed by authors. We hereby present a cerebellopontine angle NMC enlarging the eighth cranial nerve in a 3-year-old child, that histologically appeared composed of a large amount of striated muscle mixed with nerve fibers. We also provide a review of the intracranial NMC cases reported in the literature and an analysis of proposed hypotheses to explain the presence of muscle cells in nerve trunks.

Genomic Alterations of Adamantinomatous and Papillary Craniopharyngioma.

Craniopharyngiomas are rare histologically benign but clinically challenging neoplasms. To obtain further information on the molecular genetics and biology of craniopharyngiomas, we analyzed a cohort of 121 adamantinomatous and 16 papillary craniopharyngiomas (ACP, PCP). We extracted DNA from formalin-fixed paraffin-embedded tissue and determined mutational status of CTNNB1, BRAF, and DDX3X by Sanger sequencing, next generation panel sequencing, and pyrosequencing. Sixteen craniopharyngiomas were further analyzed by molecular inversion profiling (MIP); 76.1% of the ACP were mutated in exon 3 of CTNNB1 encoding for ß-catenin and there was a trend towards a worse event-free survival in cases mutated at Thr41. Next generation panel sequencing of 26 ACP did not detect any recurrent mutations other than CTNNB1 mutations. BRAF V600E mutations were found in 94% of the PCP, but not in ACP. GISTIC analysis of MIP data showed no significant larger chromosomal aberrations but a fraction of ACP showed recurrent focal gains of chromosomal material, other cases showed loss in the chromosomal region Xq28, and a third group and the PCP had stable genomes. In conclusion, the crucial pathogenetic event appears to be WNT activation in ACP, whereas it appears to be activation of the Ras/Raf/MEK/ERK pathway by BRAF V600E mutations in PCP.

Characteristics of ganglion cells in pituitary gangliocytomas.

The occurrence of ganglion cells in the sella turcica, in association or not with a pituitary adenoma, has been rarely reported. Various names have been employed for this rare entity, gangliocytoma being frequently used and recommended by WHO classification. Expression of cytokeratin in these ganglion cells has been previously occasionally reported, a very intriguing observation raising questions on the possible nature and derivation of these cells. We describe the pathological findings in three cases of growth hormone-producing adenomas, all sparsely granulated, showing the presence of a ganglion cell population admixed with an adenomatous component. A review of the literature is also provided.

MR imaging of brain pilocytic astrocytoma: beyond the stereotype of benign astrocytoma.

BACKGROUND: Pilocytic astrocytoma (PA) is the most common pediatric brain glioma and is considered the prototype of benign circumscribed astrocytoma. Despite its low malignancy, the CT and MRI features of brain PA may resemble those of much more aggressive brain tumors. Misdiagnosis of PA is particularly easy when it demonstrates MR morphological and non-morphological findings that are inconsistent with its non-aggressive nature and that overlap with the features of more aggressive brain tumors. METHOD: Basing on the evidence that the variation in the histological, genetic, and metabolic "fingerprint" for brain PA is dependent on tumor location, and the hypothesis that tumor location is related to the broad spectrum of morphological and non-morphological MR imaging findings, the authors discuss the MR imaging appearance of brain PA using a location-based approach to underline the typical and less typical imaging features and the main differential diagnosis of brain PA. A brief summary of the main pathological and clinical features, the natural history, and the treatment of brain PA is also provided. RESULT: A combination of morphological and non-morphological MR imaging features and a site-based approach to differential diagnosis are required for a pre-operative diagnosis. The new "cutting-edge" MR imaging sequences have the potential to impact the ease and confidence of pediatric brain tumor interpretation and offer a more efficient diagnostic work-up. CONCLUSIONS: Although the typical imaging features of brain pilocytic astrocytoma make radiological diagnosis relatively easy, an atypical and more aggressive appearance can lead to misdiagnosis. Knowing the broad spectrum of imaging characteristics on conventional and advanced MR imaging is important for accurate pre-operative radiological diagnosis and correctly interpreting changes during follow-up.

Minichromosome maintenance protein 7 and geminin expression: Prognostic value in laryngeal squamous cell carcinoma in patients treated with radiotherapy and cetuximab.

BACKGROUND: Minichromosome maintenance protein 7 (MCM7) is a downstream of human epidermal growth receptor (HER1) signaling. We examined MCM7, geminin, and HER1 expression in patients with laryngeal squamous cell carcinoma (SCC) treated with radiotherapy and cetuximab. METHODS: MCM7, geminin, and HER1 were evaluated by immunohistochemistry on 61 patients with laryngeal SCC. The follow-up (median, 32.1 months; range, 2-139 months) went from the beginning of therapy to tumor progression-free survival (PFS) and death (overall survival [OS]). RESULTS: MCM7, but not geminin, was associated only with HER1 expression, whereas no association was found with other clinicopathological characteristics. Patients with MCM7 high - geminin high and MCM7 high - geminin low tumor status had a risk of progression 3.1 times and 17.7 times greater, respectively, than patients with MCM7 low - geminin high tumor status. Tumor site, MCM7, and geminin were independent determinants of PFS, whereas MCM7 was an independent prognostic marker of OS. CONCLUSION: MCM7-geminin tumor status may be prognostic for patients with laryngeal SCC treated with cetuximab and radiotherapy. © 2016 Wiley Periodicals, Inc. Head Neck 39: 684-693, 2017.

Analysis of angiogenesis related factors in glioblastoma, peritumoral tissue and their derived cancer stem cells.

The formation of new blood vessels represents a crucial event under both physiological and pathological circumstances. In this study, we evaluated by immunohistochemistry, and/or Western blotting and/or quantitative real time-PCR the expression of HIF1α, HIF2α, VEGF, VEGFR1 and VEGFR2 in surgical glioblastoma multiforme (GBM) and peritumoral tissue samples obtained from 50 patients as well as in cancer stem cells (CSCs) isolated from GBM (GCSCs) and peritumoral tissue (PCSCs) of 5 patients. We also investigated the contribution of both GCSCs and PCSCs on the behavior of endothelial cells (ECs) in vitro. Immunohistochemistry demonstrated the expression of angiogenesis markers in both GBM and peritumoral tissue. In addition, in vitro tube formation assay indicated that both GCSCs and PCSCs stimulate EC proliferation as well as tube-like vessel formation. An increased migration aptitude was mainly observed when ECs were cultured in the presence of GCSCs rather than in the presence of PCSCs. These findings suggest that relevant neoangiogenetic events may occur in GBM. In particular, VEGF/VEGFR co-expression in PCSCs leads to hypothesize the involvement of an autocrine signaling. Moreover, our results suggest that both GCSCs and PCSCs own the skill of activating the "angiogenic switch" and the capability of modulating EC behavior, indicating that both cell types are either responsive to angiogenic stimuli or able to trigger angiogenic response. Together with our previous findings, this study adds a further piece to the challenging puzzle of the characterization of peritumoral tissue and of the definition of its real role in GBM pathophysiology.

Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma.

BACKGROUND: The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. METHODS: We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. RESULTS: We found two prevalent CA-SSR-1 genotypes: a homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. CONCLUSIONS: Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas.

Progenitor/Stem Cell Markers in Brain Adjacent to Glioblastoma: GD3 Ganglioside and NG2 Proteoglycan Expression.

Characterization of tissue surrounding glioblastoma (GBM) is a focus for translational research because tumor recurrence invariably occurs in this area. We investigated the expression of the progenitor/stem cell markers GD3 ganglioside and NG2 proteoglycan in GBM, peritumor tissue (brain adjacent to tumor, BAT) and cancer stem-like cells (CSCs) isolated from GBM (GCSCs) and BAT (PCSCs). GD3 and NG2 immunohistochemistry was performed in paired GBM and BAT specimens from 40 patients. Double-immunofluorescence was carried out to characterize NG2-positive cells of vessel walls. GD3 and NG2 expression was investigated in GCSCs and PCSCs whose tumorigenicity was also evaluated in Scid/bg mice. GD3 and NG2 expression was higher in tumor tissue than in BAT. NG2 decreased as the distance from tumor margin increased, regardless of the tumor cell presence, whereas GD3 correlated with neoplastic infiltration. In BAT, NG2 was coexpressed with a-smooth muscle actin (a-SMA) in pericytes and with nestin in the endothelium. Higher levels of NG2 mRNA and protein were found in GCSCs while GD3 synthase was expressed at similar levels in the 2 CSC populations. PCSCs had lower tumorigenicity than GCSCs. These data suggest the possible involvement of GD3 and NG2 in pre/pro-tumorigenic events occurring in the complex microenvironment of the tissue surrounding GBM.

Targeted next generation sequencing reveals unique mutation profile of primary melanocytic tumors of the central nervous system.

Melanocytic tumors originating in the central nervous system (MT-CNS) are rare tumors that generally have a favorable prognosis, however malignant tumors do occur. Pathogenetically MT-CNS are not well characterized. Similar to uveal melanoma and blue nevi, they frequently harbor activating GNAQ or GNA11 mutations. Rare NRAS mutations have also been reported. Other mutations have not yet been described. We analyzed 19 MT-CNS, 7 uveal melanomas and 19 cutaneous melanomas using a targeted next generation sequencing approach analyzing 29 genes known to be frequently mutated in other melanocytic tumors (in particular uveal and cutaneous melanomas). In concordance with previous studies, cutaneous melanoma samples showed frequent NRAS or BRAF mutations, as well as mutations in other genes (e.g. NF1, RAC1, PIK3CA, ARID1A). Metastasized uveal melanomas exhibited mutations in GNAQ, GNA11 and BAP1. In contrast, MT-CNS almost exclusively demonstrated mutations in GNAQ (71 %) or GNA11 (12 %). Interestingly both GNA11 mutations identified were detected in MT-CNS diagnosed as intermediate grade melanocytomas which also recurred. One of these recurrent cases also harbored an inactivating BAP1 mutation and was found to have lost one copy of chromosome 3. Our findings show that while MT-CNS do have GNAQ or GNA11 mutations, they rarely harbor other recurrent mutations found in uveal or cutaneous melanomas. Considering chromosome 3 and BAP1 loss are robust markers of poor prognosis in uveal melanoma, it will prove interesting to determine whether these genomic alterations are also of prognostic significance in MT-CNS.

Spontaneous Regression of Pineal Lesions: Ghost Tumor or Pineal Apoplexy?

BACKGROUND: Pineal apoplexy (either hemorrhagic or ischemic) may complicate the course of a tumor at this site. This event usually is characterized by an acute clinical onset and requires emergency surgical management whereas the regression of the lesion is a much rarer outcome. MATERIAL AND METHODS: Three cases of pineal vanishing tumors in the pediatric population are reported and the pertinent literature is reviewed. RESULTS: In one case, radiologic findings were consistent with a diagnosis of pineal cyst, which became symptomatic after a spontaneous hemorrhage. This event may also explain its regression after the treatment of associated hydrocephalus. In the remaining 2 cases, neuroimaging examinations disclosed a solid tumor. One of them regressed after a surgical biopsy, probably because of an ischemic evolution, whereas the last one disappeared without any medical or surgical manipulation. Neither hemorrhage nor ischemia were noticed, thus the mechanism of regression remains controversial. CONCLUSIONS: Vanishing tumors of the pineal region may occur in different circumstances, resulting from absence of any medical and surgical action to minor manipulation of the tumor to obtain a biopsy. This variety may reflect different underlying mechanisms, leading to hemorrhagic or ischemic change of the tumor and its subsequent regression, although radiological imaging may fail to document hemorrhage or ischemia.

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study.

AIM: To gather data regarding factors predicting responsiveness to pasireotide in acromegaly. PATIENTS AND METHODS: SSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR. RESULTS: None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04). CONCLUSION: The expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.

Basal cell adenoma with S-100 positive stroma: a case report and literature review.

Basal cell adenoma (BCA) of the salivary gland with presence of abundant S-100-positive stromal cells has been rarely reported. A case occurring in a 75-year-old man is presented here, as well as a review of the literature on the subject. The patient presented with a nodule in the right parotid gland. In addition to the typical features of BCA, histologically the resected tumor showed a substantial amount of stroma rich in S-100-positive spindle cells, a rarely reported finding in BCA. These cells were unreactive with a panel of myoepithelial markers, including calponin, p63, muscle-specific actin (MSA), smooth muscle actin (SMA), cytokeratin 14 (CK14), and glial fibrillary acidic protein (GFAP). Our results, in accordance with other reports, do not support a myoepithelial nature of these S-100-positive cells, and their precise nature remains elusive.