most oral mucoceles tend to occur in children or young adults , with preferential affectation of the lower lip . the typical microscopic appearance includes mucus extravasation surrounded by a wall of granulation tissue containing abundant foamy macrophages . unusual variants , such as superficial mucoceles , mucoceles with myxoglobulosis - like change and mucoceles with papillary synovial metaplasia - like change , have been reported . recently , we have seen an unusual presentation of oral mucocele being exclusively composed by macrophages showing extensive clear cytoplasmic and signet - ring cell ( src ) changes . the current case can potentially lead to diagnostic difficulties with clear cell and/or src lesions of the oral mucosa such as salivary gland or metastatic origin neoplasms . a 74-year - old man was referred presenting an asymptomatic nodular lesion on his lower lip with 1 month duration . the clinical diagnosis was oral mucocele . the medical history was noncontributory and the extra - oral examination did not show alterations . microscopic sections , at lower magnification , showed a dense population of clear cells surrounding an inner cavity [ figure 1a and b ] , which contained sparse to absent mucoid material . at the periphery , the clear cells displayed irregular infiltration into adjacent minor salivary gland parenchyma as broad sheets and cords , being supported by a dense fibrous stroma . in high - power , the cells showed clear cytoplasmic vacuolation with shrunken , pyknotic peripheral nuclei [ figure 1c ] and a src appearance , intermingled with a delicate network of small vessels [ figure 1d ] . periodic acid - schiff and mucicarmine stains revealed focal areas with homogeneous mild positivity , consistent with intracellular mucin [ figure 2a ] . despite these diagnostic approaches , definitive diagnosis still could not be achieved , because both epithelial cells and macrophages may contain cytoplasmic mucin . therefore , immunohistochemical analysis was indicated , which showed strong positivity for cd68 ( kp1 ) and cd163 [ figure 2b ] , whereas ae1/ae3 pan - cytokeratin , s100 , hmb-45 and cd1a were negative , supporting a macrophage lineage cell . the post - surgical evaluation did not reveal any abnormality and after 3 years of follow - up the patient is well without complications . histopathological features of the oral mucocele showing extensive clear cytoplasmic vacuolation and signet - ring formation ( h&e stain ) . notice a dense population of clear cells surrounding a central cavity ( a , 50 ; b , 200 ) . in high - power view ( 400 ) , observe the clear cytoplasmic vacuolation ( c ) and signet - ring cell change surrounded by a delicate capillary network ( d ) sialomucin content is demonstrated by mucicarmine staining ( a , 400 ) . by immunohistochemistry , a strong cd68 expression , as well as cd163 positivity ( inset ) , supported a macrophage lineage cells ( b , 200 ) superficial mucoceles are solitary or multiple , which microscopically show mucus extravasation at the epithelial - connective tissue interface . myxoglobulosis - like change have been reported in some oral mucoceles , in which globular hyalinized structures interspersed with mucin and mucin - laden macrophages are present into the lumen or in the extraluminal connective tissue . another unusual pattern characterized by a metaplastic transformation from granulation tissue that circumscribes the mucin pool to papillary folds exhibiting in their surface synovial - like changes has also been described . myxoglobulosis - like and papillary synovial metaplasia - like changes appear to represent incidental findings among oral mucoceles and similar with the current case , the clinical presentation for these variants did not differ significantly from the common variant of oral mucoceles . as above commented , mucus extravasation surrounded by abundant foamy macrophages is the typical microscopic appearance of the oral mucocele , being that rare variants have been reported . differently , the current case displayed numerous macrophages with extensive clear cytoplasmic vacuolation and src configuration and exhibited a diffuse distribution pattern at the peripheral areas , prompting initially a difficult differential diagnosis with clear cell / src neoplasms . accordingly , there are some studies indicating that pale foamy macrophage aggregates can mimic src adenocarcinoma and metastatic clear cell renal cell carcinoma . differential diagnosis of tumors with a predominant clear cell and/or src components in the head and neck region can be challenging . usually , clear cell / src change results from fixation artifacts , intracellular storage of glycogen , mucin or lipid , or due to paucity of organelles . the differential diagnosis of clear cell lesions of the oral mucosa includes salivary gland , sebaceous gland , melanocytic and metastatic tumors . although most exhibit distinctive microscopic characteristics , histochemistry and immunohistochemistry can be required as well as relevant clinical information in order to achieve the correct diagnosis . mucocele with clear cell features as the presented here should be distinguished from clear cell variant of salivary gland tumors such as myoepithelioma , oncocytoma , mucoepidermoid carcinoma , myoepithelial carcinoma , acinic cell carcinoma and clear cell carcinoma , not otherwise specified . the malignant salivary gland tumors exhibit the propensity for regional or distant metastasis and low recurrence . in addition , src adenocarcinoma of the minor salivary glands is other extremely rare neoplasm , which typically exhibit invasive growth pattern . by immunohistochemistry , all these salivary gland tumors are cytokeratin positive while that mucoceles are uniformly negative . moreover , it should be noted that src morphology is not always a sign of malignancy . in the oral cavity , recently it has been described an unusual lesion affecting the minor salivary glands of the lower lip and composed largely of benign epithelial srcs . melanocytic tumors containing clear cells such as balloon cell nevus and balloon cell malignant melanoma usually affect the skin of the head and neck , being rarely found in the oral cavity . only two intraoral balloon cell nevi , affecting the soft palate and buccal mucosa , have been reported . microscopically , they show densely packed proliferation of cells showing large clear , foamy or fine vacuolated cytoplasm . nevertheless , different from the current case , occasional pigmentation and/or typical melanocytes can be observed , which helps to establish the diagnosis . balloon cell change within malignant melanoma is unusual ; in these cases , malignancy is supported by cytologic pleomorphism , atypia and mitoses . by immunohistochemistry , balloon melanocytic cells show positivity for melan - a , human melanoma black ( hmb)-45 and s-100 . melanocytic markers were negative in the current case . on the other hand , although rare , clear cell variant of sebaceous tumors should also be considered ; nevertheless , most of them present typical areas containing sebaceous cells , which suggest the diagnosis . in the oral cavity , sebaceous hyperplasia , primary clear cell neoplasms from kidney , prostate , thyroid , small intestine and lung , are also able to metastasize to the oral mucosa . the most common metastatic clear cell tumor to the oral mucosa is renal cell carcinoma . this neoplasm shows an alveolar or solid architecture with varying degrees of cystic change and numerous capillaries and thin - walled blood vessels in the supporting stroma , the cytoplasm of the tumor cells is rich in lipids and glycogen . in the current case , we have found focal subepithelial areas mimicking low - grade clear cell renal cell carcinoma [ figure 1d ] . supporting this view , it has been previously reported that foamy macrophages can mimic metastatic renal cell carcinoma cells . in summary , clear cell aggregates can lead to confusion and challenge the pathologist to be able to differentiate a reactive indolent lesion from an aggressive malignant neoplasm . in these cases , the use of cd68 , cd163 and ae1/ae3 pan - cytokeratin immunomarkers is a valuable tool to avoid a misdiagnosis and arrive at an accurate diagnosis .
oral mucocele is a common reactive lesion of the oral mucosa , which microscopically exhibits mucus extravasation surrounded by a wall of granulation tissue containing abundant foamy macrophages . 
 unusual variants , such as superficial mucoceles , mucoceles with myxoglobulosis - like change and mucoceles with synovial metaplasia - like change have been reported . 
 we report a 74-year - old man who presented an asymptomatic translucent swelling on the lower labial mucosa diagnosed as mucocele showing a macrophage proliferation with extensive clear cytoplasmic vacuolation and signet - ring formation . 
 this unusual presentation expands the microscopic spectrum of the oral mucoceles and can eventually lead to differential diagnosis with primary or metastatic clear cell neoplasms . in these cases , 
 relevant clinical information , histochemistry and especially immunohistochemistry , are helpful for arriving at an accurate diagnosis .