Getting out of a mammalian egg: the egg tooth and caruncle of the echidna.

In the echidna, after development in utero, the egg is laid in the pouch and incubated for 10 days. During this time, the fetuses develop an egg tooth and caruncle to help them hatch. Using rare and unprecedented access to limited echidna pre- and post-hatching tissues, development of the egg tooth and caruncle were assessed by micro-CT, histology and immunofluorescence. Unlike therian tooth germs that develop by placode invagination, the echidna egg tooth developed by evagination, similar to the first teeth in some reptiles and fish. The egg tooth ankylosed to the premaxilla, rather than forming a tooth root with ligamentous attachment found in other mammals, with loss of the egg tooth associated with high levels of activity odontoclasts and apoptosis. The caruncle formed as a separate mineralisation from the adjacent nasal capsule, and as observed in birds and turtles, the nasal region epithelium on top of the nose expressed markers of cornification. Together, this highlights that the monotreme egg tooth shares many similarities with typical reptilian teeth, suggesting that this tooth has been conserved from a common ancestor of mammals and reptiles.

Caruncle and plica hypertrophy causing mechanical secondary acquired lacrimal duct obstruction: - SALDO update study (SUP) - paper I.

PURPOSE: To exclusively report the clinical category of mechanical secondary acquired lacrimal duct obstruction (SALDO) secondary to the caruncle and plica hypertrophy. METHODS: Prospective interventional case series involving 10 consecutive eyes with megalocaruncle and plica hypertrophy were enrolled in the study. All patients presented with epiphora secondary to a demonstratable mechanical obstruction of the puncta. All patients underwent high magnification slit-lamp photography and Fourier-domain ocular coherence tomography scans (FD-OCT) of the tear meniscus height (TMH) pre- and post-operatively at 1-month and 3-months. Caruncle and plica size, position, and their relationship to the puncta were noted. All patients underwent partial carunculectomy. Primary outcome measures were demonstrable resolution of the mechanical obstruction of the puncta and the reduction in the tear meniscus height. The secondary outcome measure was the subjective improvement of the epiphora. RESULTS: The mean age of the patients was 67 years (range: 63-72 years). The average TMH was 843.1 (range: 345-2049) microns pre-operatively and 195.1(91-379) microns at 1-month follow-up. All patients reported significant subjective improvement in epiphora at 6-months follow-up. One patient had bilateral granuloma at the surgical site at two weeks and was managed by simple excision and topical tapering steroids. Histopathology revealed hyperplastic epithelium with goblet cells with chronic inflammatory cells in the sub-epithelial region and the stroma. CONCLUSION: The role of the caruncle in the causation of mechanical SALDO needs to be carefully assessed in patients beyond the sixth decade. Excellent objective and subjective outcomes can be achieved by a partial carunculectomy and plica semilunaris excision.

Placental insufficiency and heavier placentas in sheep after suppressing CXCL12/CXCR4 signaling during implantation†.

During implantation, trophoblast cell invasion and differentiation is predominantly important to achieving proper placental formation and embryonic development. The chemokine, C-X-C motif chemokine ligand 12 (CXCL12) working through its receptor C-X-C motif chemokine receptor 4 (CXCR4) is implicated in implantation and placentation but precise roles of this axis are unclear. Suppressing CXCL12/CXCR4 signaling at the fetal-maternal interface in sheep reduces trophoblast invasion, disrupts uterine remodeling, and diminishes placental vascularization. We hypothesize these negative impacts during implantation will manifest as compromised fetal and placental growth at midgestation. To test, on day 12 postbreeding, osmotic pumps were surgically installed in 30 ewes and delivered intrauterine CXCR4 inhibitor or saline for 7 or 14 days. On day 90, fetal/maternal tissues were collected, measured, weighed, and maternal (caruncle) and fetal (cotyledon) placenta components separated and analyzed. The objectives were to determine if (i) suppressing CXCL12/CXCR4 during implantation results in reduced fetal and placental growth and development and (ii) if varying the amount of time CXCL12/CXCR4 is suppressed impacts fetal/placental development. Fetal weights were similar; however greater placental weight and placentome numbers occurred when CXCL12/CXCR4 was suppressed for 14 days. In caruncles, greater abundance of fibroblast growth factor 2, vascular endothelial growth factor A, vascular endothelial growth factor A receptor 1 (FLT-1), and placental growth factor were observed after suppressing CXCL12/CXCR4. Similar results occurred in cotyledons except less vascular endothelial growth factor in 7 day group and less fibroblast growth factor in 14 day group. Our data underscore the importance of CXCL12/CXCR4 signaling during placentation and provide strong evidence that altering CXCL12-mediated signaling induces enduring placental effects manifesting later in gestation.

Comprehensive transcriptional profiling and functional study of lymphangiogenic growth factor in placentome of early-stage pregnant water buffalo.

The aim of the present study was to evaluate the expression and localization of lymphangiogenic factors (VEGF-C and VEGF-D), their receptor (VEGFR3) and lymphatic endothelial marker (LYVE1) in buffalo placenta during early pregnancy [EP], and to investigate the functional role of lymphangiogenic growth factors in placental lymphangiogenesis. The mRNA and protein expression of VEGF-C, VEGF-D, their receptor VEGFR3 and LYVE1 showed significant expression in EP1 (29-42 days) and EP2 stages (51-82 days) both in caruncle (maternal part) and cotyledon (foetal part) of the buffalo placenta. Immunoreactivity of VEGF-C, VEGF-D and LYVE1 was observed around the endometrial gland, in lymphatics and trophoblast cells, whereas VEGFR3 mainly localized in lymphatics of the caruncle and cotyledons. Cultured trophoblast cells were treated with VEGF-C/VEGF-D (50, 100 and 150 ng/ml) and combined doses of VEGF-C and VEGF-D (150 ng/ml) each for different time durations (24, 48 and 72 h). The mRNA expression of LYVE1 and PCNA was significantly (p < .001) upregulated with VEGF-C and VEGF-D and combined treatment (@150 ng/ml), as well as significantly downregulating Caspase-3 at 48 and 72 h. Thus, the present study provides evidence that lymphangiogenic factors are expressed in buffalo placental compartments and they may play a significant role in the regulation of placental function in water buffaloes.

Transcriptomic Changes in Response to Form of Selenium on the Interferon-Tau Signaling Mechanism in the Caruncular Tissue of Beef Heifers at Maternal Recognition of Pregnancy.

We have reported that selenium (Se) provided to grazing beef cattle in an inorganic (ISe) form versus a 1:1 mixture (MIX) of inorganic and organic (OSe) forms affects cholesterol biosynthesis in the corpus luteum (CL), the abundance of interferon tau (IFNτ) and progesterone (P4)-induced mRNAs in the caruncular (CAR) tissue of the endometrium, and conceptus length at maternal recognition of pregnancy (MRP). In this study, beef heifers were supplemented with a vitamin-mineral mix containing 35 ppm Se as ISe or MIX to achieve a Se-adequate status. Inseminated heifers were killed at MRP (d 17, n = 6 per treatment) for tissue collection. In CAR samples from MIX versus ISe heifers, qPCR revealed that mRNA encoding the thyroid regulating DIO2 and DIO3 was decreased (p < 0.05) and a complete transcriptomic analysis revealed effects on the interferon JAK-STAT1/2 pathway, including decreased expression of mRNAs encoding the classical interferon stimulated genes IFIT1, IFIT2, IFIT3, IRF1, IRF9, ISG15, OAS2, and RSAD2 (p < 0.05). Treatment also affected the abundance of mRNAs contributing to the immunotolerant environment (p < 0.05). In combination, these findings suggest more advanced preparation of the CAR and developing conceptus for implantation and to evade immune rejection by the maternal system in MIX- vs. ISe-treated heifers.

Lymphoproliferative disorders in the lacrimal caruncle: report of three cases and review of literature.

This report included three cases of lymphoproliferative disorders developing from the lacrimal caruncle. The first case was an 11-year-old boy with reactive lymphoid hyperplasia in the left lacrimal caruncle. The second case was an 80-year-old woman with reactive lymphoid hyperplasia in the right lacrimal caruncle. The third case was a 77-year-old man with follicular lymphoma in the left lacrimal caruncle. Our literature review of cases with lacrimal caruncular lesions showed 11 reported cases with reactive lymphoid hyperplasia and 17 with malignant lymphoma. There had been no previous report on follicular lymphoma in the lacrimal caruncle.

Clinico-pathological correlation of lacrimal caruncle tumors: a retrospective analysis over 22 years at the University Eye Hospital Bonn.

PURPOSE: The lacrimal caruncle is composed of numerous structures including different glands as well as hair follicles. Accordingly, the spectrum of benign and malignant lesions is broad, and the clinical diagnosis is often challenging. Here we systematically analyzed excised caruncular tumors over the past 22 years with special emphasis on the clinico-pathological correlation to provide a guidance for clinicians. METHODS: Retrospective evaluation with clinico-pathologic correlation of surgically removed caruncular tumors between 1998 and 2020 at a tertiary referral center. RESULTS: Eighty-two caruncular tumors were identified in the respective period. The patients were between 11 and 85 years of age (mean, 46.8 years; median, 49 years). Nevi (n = 35), cystic lesions (n = 14), oncocytoma (n = 9), papilloma (n = 8), sebaceous gland hyperplasia (n = 8), and reactive lymphoid hyperplasia (n = 4) were observed most frequently. Besides, we are the first reporting herniated orbital fat accompanied by a pyogenic granuloma. 2.4% (n = 2) were malignant tumors (sebaceous gland carcinoma, conjunctival intraepithelial neoplasia with pyogenic granuloma). CONCLUSION: Caruncular tumors show a broad spectrum of mostly benign tumors. They can occur in patients of any age. However, 8/9 oncocytomas and both malignant lesions were detected in patients older than 60 years. Although the clinical diagnosis was confirmed in only 68.3% by the histopathological analysis, the two malignant lesions were identified as such already clinically. Caruncular lesions with a history of growth or other signs of malignancy should be excised followed by detailed histopathological examination to allow a final diagnosis and exclude rare malignant tumors with lethal potential.

Changes in arterial blood vessels and VEGF and Ang-1 expression in pregnant and non-pregnant yak uterine caruncle.

We investigated the structural features of arterial blood vessels in yak uterine caruncle and the effects of the expression of vascular regulation-related factors on angiogenesis in pregnant and non-pregnant yak uterus. Three-dimensional specimens of the uterine artery of non-pregnant and pregnant yaks were produced to observe and measure the distribution characteristics and number of arterial vessels in the uterus and caruncle in the two periods. The uterine caruncle structure was observed and analysed by haematoxylin-eosin staining. The expression features of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in the uterine caruncle were detected with immunohistochemistry, quantitative real-time PCR (qRT-PCR) and western blotting. The length and number of blood vessels in the caruncle were increased, the degree of curvature was decreased, and the folding was more complicated during pregnancy as compared with that during non-pregnancy. The immunohistochemical results demonstrated that VEGF and Ang-1 were mainly expressed strongly in the mucosal epithelial cytoplasm. The glandular lumen of the uterine gland, lymphocytes and the media and adventitia of blood vessels are widely distributed, and they are all positive. VEGF and Ang-1 mRNA and protein levels were highest in pregnancy, followed by that in the luteal phase and in the follicular phase, and three stages were significantly different (p < .05). These findings provide an anatomical reference and theoretical basis for improving the diagnosis and treatment of yak reproductive disorders and other diseases in high-altitude and low-oxygen environments.

Uptake of Phosphate, Calcium, and Vitamin D by the Pregnant Uterus of Sheep in Late Gestation: Regulation by Chorionic Somatomammotropin Hormone.

Minerals are required for the establishment and maintenance of pregnancy and regulation of fetal growth in mammals. Lentiviral-mediated RNA interference (RNAi) of chorionic somatomammotropin hormone (CSH) results in both an intrauterine growth restriction (IUGR) and a non-IUGR phenotype in sheep. This study determined the effects of CSH RNAi on the concentration and uptake of calcium, phosphate, and vitamin D, and the expression of candidate mRNAs known to mediate mineral signaling in caruncles (maternal component of placentome) and cotyledons (fetal component of placentome) on gestational day 132. CSH RNAi Non-IUGR pregnancies had a lower umbilical vein−umbilical artery calcium gradient (p < 0.05) and less cotyledonary calcium (p < 0.05) and phosphate (p < 0.05) compared to Control RNAi pregnancies. CSH RNAi IUGR pregnancies had less umbilical calcium uptake (p < 0.05), lower uterine arterial and venous concentrations of 25(OH)D (p < 0.05), and trends for lower umbilical 25(OH)D uptake (p = 0.059) compared to Control RNAi pregnancies. Furthermore, CSH RNAi IUGR pregnancies had decreased umbilical uptake of calcium (p < 0.05), less uterine venous 25(OH)D (vitamin D metabolite; p = 0.055), lower caruncular expression of SLC20A2 (sodium-dependent phosphate transporter; p < 0.05) mRNA, and lower cotyledonary expression of KL (klotho; p < 0.01), FGFR1 (fibroblast growth factor receptor 1; p < 0.05), FGFR2 (p < 0.05), and TRPV6 (transient receptor potential vanilloid member 6; p < 0.05) mRNAs compared to CSH RNAi Non-IUGR pregnancies. This study has provided novel insights into the regulatory role of CSH for calcium, phosphate, and vitamin D utilization in late gestation.

Solitary fibrous tumor of the caruncle: a solitary location.

A 78-year-old Caucasian male presented with diplopia and decreased vision in the left eye for 1 month, in addition to a painless fleshy lesion in the inner corner of the left eye for 3-month duration. His best-corrected visual acuity was 20/40 and 20/50. Slit lamp examination revealed a left medial conjunctival and caruncular lesion, measuring 6 mm by 4 mm. Histology of the excised mass showed a cellular submucosal spindle cell neoplasm without cytologic atypia and rare mitoses, immunohistologically diffusely positive for CD34 and STAT6, and negative for SMA. Based on these findings, solitary fibrous tumor was diagnosed. With the combined diagnostic power of light microscopy and immunohistochemistry, SFTs are diagnosed increasingly and more accurately in the orbit. With this first case report of a caruncular SFT, we believe that SFTs should remain on the differential for mesenchymal tumors of the conjunctiva and caruncle.

Expression and functional role of bone morphogenetic proteins (BMPs) in placenta during different stages of pregnancy in water buffalo (Bubalus bubalis).

The objective of this study was to document the expression and functional role of BMPs in the placental (caruncle; CAR, cotyledon; COT) during different stages of pregnancy in water buffalo. Samples collected from Early pregnancy 1 (EP1); Early pregnancy 2 (EP2), Mid pregnancy (MP), Late pregnancy (LP) while the third stage of oestrus cycle (NP) was taken as control. Also, the synergistic role of BMP4/BMP7 or combination on mRNA expression of vWF, PCNA, StAR, CYP11A1, 3ßHSD, and BAX were studied in trophoblast cells cultured (TCC) during an early stage. The qPCR and immunoblotting studies revealed that BMP2, BMPR1A, BMPR1B, and BMPR2 mRNA level was significantly (p < 0.05) upregulated during early pregnancy in COTs while in CARs it was significantly upregulated (p < 0.05) during all the stages of pregnancy.BMP4 mRNA level was significantly upregulated (p < 0.05) during early pregnancy in COTs as well as in CARs. BMP6 expression was significantly upregulated (p < 0.05) during early and late stages of pregnancy. BMP7 mRNA level was upregulated (p < 0.05) during the late stage of pregnancy in COTs. At 100 ng/ml, the BMP4 maximally stimulated the transcripts of StAR, CYP11A1, and 3ßHSD while BMP7 maximally stimulated the transcripts of 3ßHSD that paralleled with P4 accretion in the media (P < 0.05). BMP4 as well as BMP7 upregulated the transcripts of PCNA, vWF, and downregulated BAX in the TCC (P < 0.05). In conclusion, BMPs are expressed in a regulated manner with stage-specific differences in the placenta and promotes the angiogenesis, proliferation, cell survivability, and steroidogenesis thereby regulating placental function in an autocrine/paracrine manner in water buffalo.

Differential gene expression profiling of endometrium during the mid-luteal phase of the estrous cycle between a repeat breeder (RB) and non-RB cows.

BACKGROUND: Repeat breeding directly affects reproductive efficiency in cattle due to an increase in services per conception and calving interval. This study aimed to investigate whether changes in endometrial gene expression profile are involved in repeat breeding in cows. Differential gene expression profiles of the endometrium were investigated during the mid-luteal phase of the estrous cycle between repeat breeder (RB) and non-RB cows using microarray analysis. METHODS: The caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and non-RB cows on Day 15 of the estrous cycle (4 cows/group). Global gene expression profiles of these endometrial samples were analyzed with a 15 K custom-made oligo-microarray for cattle. Immunohistochemistry was performed to investigate the cellular localization of proteins of three identified transcripts in the endometrium. RESULTS: Microarray analysis revealed that 405 and 397 genes were differentially expressed in the CAR and ICAR of the ipsilateral uterine horn of RB, respectively when compared with non-RB cows. In the contralateral uterine horn, 443 and 257 differentially expressed genes were identified in the CAR and ICAR of RB, respectively when compared with non-RB cows. Gene ontology analysis revealed that genes involved in development and morphogenesis were mainly up-regulated in the CAR of RB cows. In the ICAR of both the ipsilateral and contralateral uterine horns, genes related to the metabolic process were predominantly enriched in the RB cows when compared with non-RB cows. In the analysis of the whole uterus (combining the data above four endometrial compartments), RB cows showed up-regulation of 37 genes including PRSS2, GSTA3 and PIPOX and down-regulation of 39 genes including CHGA, KRT35 and THBS4 when compared with non-RB cows. Immunohistochemistry revealed that CHGA, GSTA3 and PRSS2 proteins were localized in luminal and glandular epithelial cells and stroma of the endometrium. CONCLUSION: The present study showed that endometrial gene expression profiles are different between RB and non-RB cows. The identified candidate endometrial genes and functions in each endometrial compartment may contribute to bovine reproductive performance.

Results of surgical excision of urethral prolapse in symptomatic patients.

AIM: Here, we present the clinical presentation and surgical outcomes of women with symptomatic urethral prolapse presenting to our institution over 20 years, and seek to provide treatment recommendations for management of symptomatic urethral prolapse and caruncle. METHODS: A retrospective review of medical records from female patients who underwent surgery for symptomatic urethral prolapse from June 1995 to August 2015 was performed. Surgical technique consisted of a four-quadrant excisional approach for repair of urethral prolapse. RESULTS: A total of 26 patients were identified with a mean age of 38.8 years (range 3-81). The most common presentations were vaginal bleeding, hematuria, pain, and dysuria. All patients underwent surgical excision of urethral prolapse via a standard approach. Follow-up data was available in 24 patients. Six patients experienced temporary postoperative bleeding, and one patient required placement of a Foley catheter for tamponade. One patient experienced temporary postoperative urinary retention requiring Foley catheter placement. Three patients had visible recurrence of urethral prolapse, for which one later underwent re-excision. CONCLUSION: Surgical excision of urethral prolapse is a reasonable treatment option in patients who have tried conservative management without relief, as well as in those who present with severe symptoms. Possible complications following excision include postoperative bleeding and recurrence, and patients must be counseled accordingly. In this work, we propose a treatment algorithm for symptomatic urethral prolapse.

Bilateral lacrimal caruncle lesions.

A 65-year-old man was referred to our hospital for the treatment of a lesion on the medial lacrimal canthus of both eyes. He had a history of perinuclear anti-neutrophil cytoplasmic antibodies, i.e., pANCA-positive interstitial pneumonia. Orbital magnetic resonance imaging excluded space occupying lesions, and laboratory testing excluded thyroid-related diseases. The masses were excised, and histopathological examinations showed sebaceous gland hyperplasia and inflammatory changes around the gland. In addition, the specimen from the left eye showed a retention cyst possibly caused by an infection. It was also possible that the use of steroid was involved in the development of the lesions. A relationship between the ANCA and the lesions was not completely eliminated.

Surgical result of pterygium extended removal followed by fibrin glue-assisted amniotic membrane transplantation.

BACKGROUND/PURPOSE: To report the recurrence rate and cosmetic results of conjunctival wound edge and caruncle, and complications after pterygium extended removal followed by fibrin glue-assisted amniotic membrane transplantation. METHODS: A prospective interventional cohort study enrolled 57 (58 eyes) patients undergoing pterygium extended removal followed by fibrin glue-assisted amniotic membrane transplantation. All patients received postoperative follow-up for at least 12 months. Recurrence rate was graded from 1 to 4, and cosmetic results of conjunctival edge and caruncle were graded from 1 to 5. RESULTS: The cohort included 48 eyes with nasal pterygium, 5 eyes with temporal pterygium, and 5 eyes with double pterygium. There were 81.0% (n=47), 0% (n=0), 12% (n=7), and 7% (n=4) of eyes with Grades 1-4 recurrence, respectively. The cosmetic results of conjunctival wound edge and caruncle in cases with nasal pterygium showed 59.3% (n=32), 14.8% (n=8), 9.3% (n=5), 16.6% (n=9), and 0% (n=0) of eyes with Grades 1-5 morphology, respectively. Overall, 5.1% (n=3), 3.4% (n=2), 3.4% (n=2), 3.4% (n=2), 1.7% (n=1), 6.9% (n=4), and 1.7% (n=1) of patients suffered from postoperative pyogenic granuloma, transient diplopia, permanent motility restriction, steroid glaucoma, fat prolapse, subamniotic membrane hemorrhage, and early detachment of amniotic membrane, respectively. CONCLUSION: Pterygium extended removal followed by fibrin glue-assisted amniotic membrane transplantation results in low recurrence, satisfactory cosmetic results and a low incidence of additional complications.

Steatocystoma simplex of the lacrimal caruncle: a case report.

BACKGROUND: This is the third reported case of a steatocystoma simplex in the lacrimal caruncle. CASE PRESENTATION: A 60-year-old male presented with a history of a slowly progressing mass in the right lacrimal caruncle since several years before his initial visit. At the first examination, a yellowish, relatively smooth surface mass was observed in the right lacrimal caruncle. The caruncular mass was completely removed under local anesthesia. The pathological findings of this mass were consistent with a steatocystoma. At the 6-month follow-up, there was no sign of recurrence or development of the steatocystoma or any other masses. CONCLUSION: Although steatocystoma simplex rarely occurs in the lacrimal caruncle, it needs to be considered as a possible diagnosis for patients with a mass lesion in the caruncle.

Angiomatous Urethral Caruncle After Ureteroscopy: A Case Report.

Urethral caruncle is a rare condition. Although relatively common in postmenopausal women, its occurrence after a urological endoscopic procedure is unusual. Here, we report the case of a postmenopausal woman who presented with a symptomatic urethral caruncle two weeks after a ureteroscopy for a right ureteral calculus. Treatment consisted of surgical excision of the mass after the failure of local estrogen application, and the postoperative aesthetic and functional result was satisfactory. Through a review of the literature, the etiological, diagnostic, and therapeutic aspects of this pathology will be discussed.

Pigmented Nevus of the Caruncle and Plica Semilunaris: A Case Report.

Conjunctival nevi are benign, heterogenous tumors that uncommonly arise from the lacrimal caruncle and plica semilunaris. We present a case of a patient diagnosed and managed for an unusual, pigmented nevus of the left caruncle involving the plica. An 84-year-old woman presented with a rapidly growing, pigmented lesion in her left nasal canthus. Examination demonstrated a raised, dark, pigmented area arising from the left caruncle and seeming to involve the plica semilunaris without scleral extension. The lesion was completely excised for histopathology, which confirmed the diagnosis of a compound nevus with pigment incontinence. Given the unfavorable anatomical position and prognostic significance in the case of malignancy, pigmented caruncular lesions should be thoroughly investigated with a low threshold for surgical removal.

Caruncle dysgeneses - A case series.

Purpose: Caruncle dysgeneses are extremely rare and must be differentiated from caruncular and conjunctival tumors. Very few case reports with histopathological descriptions exist. In this case series, four patients with five caruncle dysgeneses, two with histopathological findings, are characterised. Observations: Patient 1, a 26-year-old woman, presented with a conjunctival change at the left lower eyelid she had first noticed seven months earlier. She reported foreign body sensation and itching. On her left eye was a subtarsal conjunctival tumour measuring approximately 4 × 4 mm with whitish sebaceous gland-like inclusions located almost in the fornix morphologically resembling the nearby caruncle. The patient was asymptomatic after excision. Histopathological examination of the excised tissue showed non-keratinizing squamous epithelium with goblet cells. Subepithelially, there was lymphoplasmacytic cellular infiltration with intervening epidermal cysts adjacent to sebaceous glands and underlying adipose tissue, but no hair follicles or sweat/lacrimal glands. The epidermal cysts contained scattered hairs. A diagnosis of supernumerary caruncle was made.Patient 2, a 56-year-old woman, was referred for evaluation of a caruncle tumour that was reported to be present since childhood. Clinically the 5 × 5 mm measuring tumour appeared yellowish and less reflective compared to the normal caruncle tissue. Histopathologically, non-keratinizing squamous epithelium with goblet cells was found. In the area of more exposed tumour tissue, there were significantly fewer goblet cells and incipient keratinization of the superficial epithelial layers. Subepithelially, sebaceous glands and adipocytes were present. Hair follicles or sweat/lacrimal glands were not evident. A diagnosis of megacaruncle was made.Patient 3, a 58-year-old woman with Goldenhar syndrome, was clinically diagnosed with a supernumerary caruncle on the right eye as an incidental finding.Patient 4, a 24-year old man, clinically presented with a megacaruncle on the right eye and a supernumerary caruncle on the left. Conclusions: Caruncle dysgeneses are often asymptomatic and have to be differentiated from other caruncular and conjunctival tumors. If they are present, attention should be paid to signs of an oculo-auriculo-vertebral spectrum as Goldenhar syndrome. In case of unclear findings or complaints, excision with subsequent histopathological examination is required.