Spontaneous tumor regression following COVID-19 vaccination.

Vaccination against COVID-19 is critical for immuno-compromised individuals, including patients with cancer. Systemic reactogenicity, a manifestation of the innate immune response to vaccines, occurs in up to 69% of patients following vaccination with RNA-based COVID-19 vaccines. Tumor regression can occur following an intense immune-inflammatory response and novel strategies to treat cancer rely on manipulating the host immune system. Here, we report spontaneous regression of metastatic salivary gland myoepithelial carcinoma in a patient who experienced grade 3 systemic reactogenicity, following vaccination with the mRNA-1273 COVID-19 vaccine. Histological and immunophenotypic inspection of the postvaccination lung biopsy specimens showed a massive inflammatory infiltrate with scant embedded tumor clusters (<5%). Highly multiplexed imaging mass cytometry showed that the postvaccination lung metastasis samples had remarkable immune cell infiltration, including CD4+ T cells, CD8+ T cells, natural killer cells, B cells, and dendritic cells, which contrasted with very low levels of these cells in the prevaccination primary tumor and lung metastasis samples. CT scans obtained 3, 6, and 9 months after the second vaccine dose demonstrated persistent tumor shrinkage (50%, 67%, and 73% reduction, respectively), suggesting that vaccination stimulated anticancer immunity. Insight: This case suggests that the mRNA-1273 COVID-19 vaccine stimulated anticancer immunity and tumor regression.

A case of a CD56-expressing ectomesenchymal chondromyxoid tumor of the tongue: potential diagnostic usefulness of commonly available CD56 over CD57.

Ectomesenchymal chondromyxoid tumors (ECTs) are rare. Only approximately 55 cases have been reported in the English literature. Distinguishing ECTs from soft tissue myoepithelioma (STM) is often difficult owing to morphological and immunohistochemical similarities. Here, we present a case of an ECT arising from the anterior dorsum of the tongue in a 24-year-old woman. Grossly, the tumor was soft, had a myxoid appearance, and measured 8×7×7 mm. Microscopically, it was well-demarcated, lacked a fibrous capsule, and predominantly consisted of short, spindle to ovoid cells in a myxoid background. Vimentin, glial fibrillary acidic protein (GFAP), and S-100 protein were strongly positive on immunohistochemical analysis. While CD56 was moderately immunopositive, cytokeratin (AE1/AE3) and alpha-smooth muscle actin (αSMA) showed focal weak positivity. Thus, the immunohistochemical findings suggested a diverse immunophenotype, indicating mesenchymal (vimentin and αSMA positive), neurogenic (S100, GFAP, and CD56 positive), and epithelial differentiation (cytokeratin positive). This reflected the fact that ECTs probably arise from uncommitted ectomesenchymal cells that have the potential for multilineage differentiation. The immunohistochemical staining pattern observed for ECTs slightly differs from that of STMs. Strongly positive staining for GFAP and weakly positive staining for cytokeratin are observed in ECTs, whereas the opposite is typically observed for STMs. These findings indicated that the patterns of expression on immunohistochemistry differ between ECTs and STMs, although inevitably, there was some overlap. Thus, CD56 expression in the case presented here is noteworthy, and it could potentially become an adjunct diagnostic marker for ECT instead of previously used CD57.

Increased expression of C5a receptor (CD88) mRNA in canine mammary tumors.

Mammary tumors are among the most common neoplastic conditions in dogs, and there is evidence that inflammation plays a role in the development of some tumor types in dogs. The complement system is a major participant in the inflammatory process and the complement activation component, C5a, is a potent inflammatory peptide. This study investigated the mRNA expression of the major receptor for C5a (C5aR; CD88) in histopathological samples of canine mammary tumors by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using canine-specific primers for CD88. A total of seven canine mammary tumors (four malignant carcinomas, two benign mixed mammary tumors, and one myoepithelioma) and eight normal mammary glands were analysed. All the tumor samples expressed low levels of CD88 mRNA, while none of the normal mammary tissues showed any detectable expression. These preliminary results suggest that C5a-CD88 interaction may play a contributory role in the inflammatory response associated with mammary tumor development in dogs. Further studies investigating the mechanisms behind complement activation and C5a receptor expression in canine mammary tumors are warranted.

Clinical, histological and immunohistochemical features of ectomesenchymal chondromyxoid tumor.

OBJECTIVE: Ectomesenchymal chondromyxoid tumor is a rare oral soft tissue neoplasm that should be differentiated from other neural and chondromyxoid entities. The aim of this study was to report the clinical, histological, and immunohistochemical features of 3 additional cases of this condition. METHODS: Clinical data were obtained from the clinical records and all cases were evaluated through light microscopy and immunohistochemistry to cytokeratins, vimentin, S100 protein, desmin, smooth muscle actin, and glial fibrilary acidic protein. RESULTS: All 3 cases affected the tongue as a long-lasting submucosal swelling and were managed through conservative surgery. They all showed myxoid and chondroid histological patterns, and vimentin, S100, and glial fibrilary acidic protein immunoexpression. CONCLUSIONS: These findings reinforce the typical features of ectomesenchymal chondromyxoid tumor previously described, helping to confirm and establish the clinical, histopathological, and immunohistochemical profile of this uncommon lesion.

Relative paucity of gross genetic alterations in myoepitheliomas and myoepithelial carcinomas of salivary glands.

The diagnosis of salivary gland myoepithelioma, an entity with heterogeneous cytomorphology and inconsistent immunophenotype, rests on conventional histology. However, the clinical course cannot be predicted reliably from cytomorphological and immunophenotypic analysis. The present study determined the immunophenotype of a representative series of 12 myoepitheliomas and 21 malignant myoepitheliomas. Among the seven markers tested, antibodies against cytokeratins 5/6, S-100 protein, and vimentin produced the most consistent reactivity profile. Comparative genomic hybridization (CGH) profiles of 12 myoepitheliomas showed chromosomal losses in three of 12 cases. In myoepithelial carcinomas, however, ten of 19 tissues investigated by CGH lacked detectable cytogenetic aberrations. In five cases, aberrations involved chromosome 8, in line with observations in salivary gland carcinomas of other differentiation. One case that was represented in three separately localized manifestations of the disease proved informative as to the relevance of gross aberration for tumour development, as these tumours differed in their CGH profiles. Staining for cytokeratins 5/6 is a useful addition to the established immunohistological marker panel in the work-up of myoepitheliomas, because of its reliable expression in most cases and because it may underline the epithelial nature of the lesion. CGH proved to be of limited value as a diagnostic adjunct; the presence of numerous gross cytogenetic aberrations should raise the suspicion of malignancy. The low frequency of aberrations detectable by CGH in overtly malignant myoepithelial neoplasms suggests that gross cytogenetic alterations were acquired in the course of tumour progression and points to the relevance of genetic changes not resolved by CGH.

Expression of CD44 standard and variant isoforms in parotid gland and parotid gland tumours.

In this study, we investigated the distribution of the standard form of the CD44 (CD44s) cell adhesion molecule and of its v3 and v6 isoforms in samples of foetal and adult parotid gland tissue, in comparison with samples of parotid gland adenomas and carcinoma ex pleomorphic adenoma. Foetal parotid gland showed CD44s and CD44v3 expression in the peripheral small primordial ducts and acini, while CD44v6 was only focally expressed. Adult parotid gland tissue showed a similar distribution of CD44s and variants, with a predominant expression in acinar structures and a weaker expression at duct level. In parotid gland adenomas, a diffuse and intense expression of CD44s and variants 3 and 6 was observed only in pleomorphic adenomas, while expression of CD44s was prevalent in Warthin's tumour, myoepithelioma and oncocytoma. The malignant areas of carcinoma ex pleomorphic adenoma showed a markedly decreased expression of CD44v3 and CD44v6 in comparison with the adjacent pleomorphic adenoma component. In conclusion, the prevalent expression of CD44s and variants in pleomorphic adenoma in comparison with other adenomas may be related to the abundant extracellular matrix production present in these tumours, while loss of CD44v3 and CD44v6 associated with the onset of carcinoma ex pleomorphic adenoma could promote stromal invasion, eventually contributing to the development of distant metastases.

Plasmacytoid myoepithelioma of the soft palate. Report of a case with cytologic, immunohistochemical and electron microscopic studies.

BACKGROUND: The plasmacytoid variant is a rare and controversial subtype of myoepithelioma that lacks myogenic differentation and the cytologic findings of which have not been reported previously. CASE: A 46-year-old man presented with a painless tumor located in the soft palate. Fine needle aspiration cytology (FNAC) showed odd-shaped cellular aggregates and single cells with round nuclei and finely granular cytoplasm resembling plasma cells together with strands of metachromatic stroma. The light, immunohistochemical and ultrastructural studies performed on the surgical specimen confirmed the initial cytologic diagnosis. CONCLUSION: Recognition of the cytologic findings of plasmacytoid myoepithelioma on needle aspirates allows a reliable and quick diagnosis that prompts correct management.

Expression of the adenocarcinoma-related antigen recognized by monoclonal antibody 44-3A6 in salivary gland neoplasias.

The monoclonal antibody 44-3A6 detects a cell-surface protein that has been shown to be a useful marker in distinguishing adenocarcinomas from other histologic tumor types in a variety of tissues. The objective of this study was to determine whether 44-3A6 could be used as a tool in the classification of salivary gland neoplasms. These complex tumors share overlapping pathologic features but distinct clinical outcomes. This study used 44-3A6 to immunohistochemically describe the pattern and frequency of this antigen in salivary gland neoplasms. Formalin-fixed, paraffin-embedded tissue sections of 22 benign and 26 malignant salivary tumors were evaluated. The patient population consisted of 25 (52.1%) women and 23 (47.9%) men selected from archival pathology files to reflect a range of salivary gland diseases. Normal surrounding salivary glands were found to have intense focal staining almost exclusively localized to ductal luminal cells. There was little staining of either myoepithelial or acinar cells. A wide spectrum of expression was found between and within tumor types, but a trend toward more expression of this antigen with decreasing differentiation was seen. A significant increase in staining was also seen in those tumors with ductal differentiation (n = 41) as opposed to those with predominantly acinar (i.e., acinic cell carcinoma) or myoepithelial (i.e., myoepithelioma; n = 8) differentiation (2.6 vs. 1.3, p < 0.05). No correlation was found between staining intensity and facial paralysis, pain, skin involvement, TNM stage, residual disease, or disease-free or total survival. Therefore this antigen appears to designate a duct luminal phenotype in normal and neoplastic salivary tissues.

Assessment of invasion in breast lesions using antibodies to basement membrane components and myoepithelial cells.

This paper describes immunostaining of consecutive sections from 15 cases of fibrocystic change of the breast (including 2 examples of intraductal papilloma), 4 ductal carcinomas-in-situ and 17 invasive carcinomas (4 tubular, 1 papillary, 2 lobular and 10 infiltrating ductal, NOS) with antisera to components of the basement membrane (BM), type IV collagen and laminin, and with the muscle antibodies actin and muscle-specific actin. A simple digestion technique was developed to improve the clarity of BM staining with these antibodies. The BM stains facilitated identification of small invasive foci through breaks in the BM in 2 of the cases which had been reported as pure intraductal carcinoma. Tubular carcinomas were surrounded by abnormal, fragmented, and focally discontinuous BM, a feature which could be used to distinguish this well-differentiated breast carcinoma sub-type from sclerosing adenosis, in which individual acini were invariably surrounded by a continuous BM. BM staining emphasized the fibrovascular core of intraductal papillomas, whereas the BM layer was absent in intraductal, cytologically malignant, papillary projections. Similarly, myoepithelial cells, stained with antisera to muscle actins, were identified in a continuous layer surrounding benign epithelial proliferations. These immunohistochemical staining techniques may thus assist the diagnostic histopathologist in differentiating between benign epithelial proliferations of the breast and well-differentiated invasive breast carcinoma, and in identifying foci of microinvasive carcinoma.

Normal and neoplastic myoepithelial cells in salivary glands: an immunohistochemical study.

To determine the difference between normal and neoplastic myoepithelial cells, we performed immunoperoxidase staining for contractile proteins (actin and myosin) and intermediate filament proteins (vimentin and 55- to 57-kilodalton keratin) on paraffin sections from salivary gland tumors. Normal myoepithelial cells were positive for actin and myosin but negative for vimentin and keratin. Outer tubular cells of organoid double-layered tubular structures seen in pleomorphic and monomorphic adenoma and adenoid cystic carcinoma, and "cyst"-lining cells and outermost cells of adenoid cystic carcinoma were occasionally positive for actin and myosin. These outer tubular cells, "cyst"-lining cells, and outermost cells were considered to be neoplastic myoepithelial cells. However, their stainability was much lower than that of normal myoepithelial cells. On the other hand, these neoplastic myoepithelial cell were always positive for vimentin. "Mesenchymal" cells and hyaline cells of pleomorphic adenoma and indifferent cells of adenoid cystic carcinoma were negative for both actin and myosin but positive for vimentin and occasionally also positive for keratin. The significance of vimentin staining in neoplastic myoepithelial cells and the coexpression of vimentin and keratin in some tumor cells is discussed.

Myoepithelioma of the lung.

This report describes the first documented case (to our knowledge) of a myoepithelioma occurring in the lung. The neoplasm showed histologic features identical to those described in myoepitheliomas of major and minor salivary glands. The histologic diagnosis was confirmed ultrastructurally by the presence of longitudinal cytoplasmic bundles of 6-nm myofilaments and was supported immunologically by the expression of S100 protein.

Various expressions of modified myoepithelial cells in salivary pleomorphic adenoma. Immunohistochemical studies.

Variant expressions of modified myoepithelial cells in salivary pleomorphic adenomas are described as determined by immunohistochemical techniques which visualized the distributions of S-100 protein, intermediate-sized filament proteins (keratin, vimentin, and desmin), and contractile proteins (myosin and actin), as well as lysozyme and lactoferrin. Immunohistochemical staining patterns of S-100 protein were basically used to classify modified myoepithelial cells, along with histologic criteria. Histochemical modifications of myoepithelial cells in pleomorphic adenoma of salivary glands could be divided into a) reactive, b) transformed, and c) neoplastic myoepithelial cells. Reactive myoepithelial cells were stromal-like cells which displayed an intense S-100 protein reaction. Transformed myoepithelial cells were negative or slightly positive for S-100 protein; they were located in the outer zone of tubular or duct-like structures and were spindle-shaped. The inner round cells of tubular and ductal structures, which could be ductal origin, gave intense keratin staining, as well as marked reactions for lysozyme and lactoferrin. Neoplastic myoepithelial cells were plasmatoid or fibrous types of cells and contained abundant S-100 protein and vimentin. These cells were termed "myoepithelioma" as in classical diagnosis.

S-100 protein and myoepithelial neoplasms.

Besides advancing our knowledge of histogenesis, immuno-cytochemical studies of salivary gland tumors have added an important objective component to the diagnosis and classification of the tumors. Cellular localization of S-100 protein now allows identification of myoepithelial cells and tumors composed of these cells. The four tumors presented in this report illustrate the diagnostic advantages afforded by S-100 protein immunocytochemistry.

Myoepithelioma of the breast: histologic, immunologic, and electromicroscopic appearance.

This report describes the histologic, immunologic, and ultrastructural features of a distinctive spindle-cell tumor of the female breast interpreted as pure myoepithelioma. By light microscopy, the tumor showed the mammary parenchyma replaced by bundles of fusiform cells, which cytoplasms contained myosin and actin, demonstrated immunologically. Ultrastructurally, the spindle cells were joined by mature desmosomes and presented parallel bundles of microfilaments and remnants of basal lamina.

Myoepithelioma of the palate in a child.

Salivary gland myoepitheliomas are rare tumors accounting for less than 1% of neoplasms of the salivary glands. We report a myoepithelioma arising in the palate of an 8-year-old female, the youngest case in the literature. Electron microscopic and immunohistochemical studies support the myoepithelial origin of this tumor.

Malignant myoepithelioma (myoepithelial carcinoma) of the breast: an ultrastructural and immunocytochemical study.

This report describes the light (LM) and electron microscopic (EM) features and the results of an indirect immunofluorescence study (IF), the latter using monoclonal and monospecific antibodies to cytoskeletal proteins, of a malignant, invasive and metastatic breast myoepithelioma. A 53-year-old female underwent mastectomy for a large necrotic mammary tumor that had invaded the overlying skin. By LM, the neoplasm was composed of interlacing bundles of large, elongated and interspersed stellate cells with acidophilic cytoplasm. The neoplastic cells displayed a moderate degree of anaplasia, high mitotic activity, and strong tendency for necrosis. Stromal desmoplasia was marked, especially toward the center of the neoplasm. By IF, the tumor cells revealed bright cytoplasmic fluorescence with antibodies to actin, prekeratin, and cytokeratin. A few scattered spindle cells, which stained with the anti-vimentin and anti-actin anti-bodies, most likely represented stromal myofibroblasts. The anti-desmin reaction was negative. By EM, the neoplasm was composed of variably differentiated, elongated and stellate myoepithelial cells connected by desmosomes, enveloped by remnants of basal lamina, and containing pinocytotic vesicles, a well-developed rough endoplasmic reticulum, large Golgi areas, aggregates of intermediate filaments that were often arranged in dense curvilinear bundles (tonofilaments), and bundles of microfilaments with fusiform, dense bodies. The combined LM, EM, and IF study of this mammary tumor establishes its myoepithelial origin and, thus, identifies it as myoepithelial carcinoma distinct from other spindle cell breast tumors. This neoplasms was locally invasive and cytologically malignant; moreover, its malignancy was further confirmed by the development of lung and pleural metastases.