Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome: Relapse and Tonsillar Regrowth After Childhood Tonsillectomy.

OBJECTIVES/HYPOTHESIS: Tonsillectomy is an effective treatment for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, but the role of adenoidectomy, as well as later tonsillar regrowth, is unclear. To find out if the volume of lymphoid tissue is pivotal to the efficacy, we analyzed the association between the relapse of the symptoms of PFAPA syndrome and regrowth of tonsillar tissue after tonsillectomy or adenotonsillectomy. STUDY DESIGN: Prospective cohort study of operated PFAPA pateints. METHODS: We invited all patients that had undergone tonsillectomy or adenotonsillectomy due to PFAPA syndrome at the Oulu University Hospital, Oulu, Finland, between the years 1990 and 2007, at the age of ≤12 years, to a follow-up visit, after an average period of 9.8 years after their diagnoses. Out of the 132 invited, 94 (71%) participated in the follow-up study. RESULTS: At the follow-up study visit, 5 (5%) of the 94 PFAPA syndrome cases experienced recurrent fevers. The regrowth of palatine tonsillar tissue was seen in four of them (80%) as compared to 19/89 (21%) of symptom-free patients (P = .006). Two of the patients with clear PFAPA relapse at the time of the study visit were reoperated with clear effect on the symptoms. At the time of the study visit, 59/63 (94%) of the patients who had undergone adenotonsillectomy and 30/31 of the patients (97%) who had undergone tonsillectomy earlier were free of fever flares (P = .99). CONCLUSION: Palatine tonsil regrowth was associated with PFAPA syndrome relapse after tonsillectomy. Reoperation might be a treatment option in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2149-E2152, 2021.

Identifying cohort differences in children undergoing partial intracapsular tonsillectomy vs traditional tonsillectomy for sleep disordered breathing.

OBJECTIVE: Partial intracapsular tonsillectomy (PIT) is a well-established technique for reducing post-operative morbidity in pediatric patients with sleep disordered breathing (SDB). Although tonsillar re-growth rates are reported as low, risks of symptom recurrence or need for completion tonsillectomy are clear disadvantages when compared to traditional tonsillectomy (TT). We aim to identify cohort differences to better guide clinical decision making and identify patient-specific factors that may influence this decision. A secondary aim was to evaluate potential risk factors for tonsillar regrowth. METHODS: Retrospective chart review of pediatric patients who underwent TT or PIT for SDB between 2015 and 2019 at a tertiary care academic medical center. Records were reviewed for age, gender, race, body mass index, comorbidities, diagnosis, apnea-hypopnea index, pre-operative Brodsky tonsil size, length of stay, post-operative hemorrhage, tonsillar regrowth, symptom recurrence, and need for completion tonsillectomy. RESULTS: 315 patients were included: 174 underwent TT and 141 underwent PIT. Patients undergoing TT were more likely to have a sleep study showing OSA (OR 3.01, p < 0.0001), asthma (OR 4.28, p = 0.000124), and other comorbidities (OR 4.06, p = 0.0258). The overall complication rate was 4.44% (14/315). Tonsillar regrowth was exclusive to the PIT group, occurring in 7/141 patients (4.96%). Age ≤4 years was significantly associated with increased risk of tonsillar regrowth (≤4 years: 7.69%, >4 years: 0%; p = 0.049). Race and pre-operative tonsil size were not associated with regrowth. CONCLUSIONS: Our study supports the low incidence of tonsillar regrowth in PIT and suggests an association with younger age. Moreover, we found that patients undergoing TT are more likely to be older, have OSA, asthma, and other comorbidities.

Fetal and early postnatal development of the porcine tonsils of the soft palate.

Tonsils are mucosa-associated lymphoid tissues located at the openings of the gastrointestinal and respiratory tracts, which play a key role in the surveillance of inhaled or ingested pathogens and can concurrently be reservoirs of infectious agents. Therefore, tonsils are important for the immunology and hygiene management of domestic animals, including pigs. However, the process of their fetal developmental has been poorly described, at least in part, because rodents lack tonsils. Therefore, we performed a histological analysis of porcine tonsils of the soft palate from 60 to 100 days of gestation (DG) and from 2 to 14 days post partum (DP). This analysis showed that lymphoid aggregations first appear at DG65, gradually develop during the fetal stage, and expand after birth. In addition, the mRNA expression of chemokine genes involved in lymphoid aggregation and localization was analyzed. CCL19 expression showed the most marked increase and a sharp peak after birth. CCL21 expression changed moderately but showed an interesting bimodal pattern. CXCL13 expression steadily increased throughout the study period. Thus, we demonstrated the mRNA expression of chemokine characteristically changed accompanying tonsillar development.

The porcine tonsils and Peyer's patches: A stereological morphometric analysis in conventionally and artificially reared piglets.

Selection for prolificacy in modern pig farming has resulted in increasing litter sizes. Since rearing large litters is challenging, artificial rearing of piglets with a milk replacer is an alternative strategy. It is hypothesized that the development of the piglets' mucosa-associated lymphoid tissues (MALT) is affected by these artificial conditions. Therefore, the stereologically estimated volumes of the tonsil of the soft palate, and the lingual, nasopharyngeal and paraepiglottic tonsils, as well as the jejunal and ileal Peyer's patches were statistically compared at day 21 postpartum between six conventionally reared piglets and six piglets that were artificially reared from day 7 onwards. In addition, six 7-day-old sow-fed piglets were examined to evaluate the effect of age. All tonsils and Peyer's patches significantly increased in volume with age. The rearing strategy had no significant effect on the volumes of the tonsil of the soft palate and the lingual tonsil. The former tonsil was by far the largest with a mean volume of 967.2 ± 122.4 mm3 and 822.3 ± 125.4 mm3 in the conventionally and artificially reared piglets, respectively. The lingual tonsil only measured 9.4 ± 6.4 mm3 and 6.3 ± 2.6 mm3 in conventionally and artificially reared groups, respectively. In contrast, the rearing strategy did affect the volumes of the nasopharyngeal and paraepiglottic tonsils, which had a mean volume of 137.1 ± 32.4 mm3 and 84.4 ± 26.9 mm3, and 30.7 ± 7.8 mm3 and 20.0 ± 3.9 mm3 in conventionally and artificially reared piglets, respectively. The rearing strategy did not affect the development of the Peyer's patches. At day 21, the jejunal Peyer's patches of the conventionally and artificially reared piglets presented a volume of 1.6 ± 0.4 cm3 and 1.3 ± 0.2 cm3, respectively. The volumes of the ileal Peyer's patch amounted to 15.1 ± 3.0 cm³ in conventionally reared piglets and 12.0 ± 2.6 cm³ in artificially reared piglets at day 21. The results showed that artificial rearing hampers the morphological development of the tonsils that are exposed to inhaled antigens, but the voluminous lymphoid tissues that sample oral antigens are not influenced. Since it is unlikely that the observed differences in both tonsils are due to the milk replacer, artificial rearing could be a valuable alternative for raising large litters. In addition, the presence of developing MALT in piglets allows for investigating the value of nasal and oral vaccination in this species for human or veterinary purposes.

Patterns of adenoid and tonsil growth in Japanese children and adolescents: A longitudinal study.

Lymphoid tissues, such as adenoids (Ad) and tonsils (Tn), are suggested to undergo hypertrophy during childhood and involution in adulthood. Enlargement of Ad and Tn can cause transient obstruction of the respiratory airways, thus inducing obstructive sleep apnoea. To date, the standard Ad and Tn sizes have not been reported, and there are no explicit objective criteria for evaluating their sizes or deducing whether they have enlarged, reduced, or remained constant over time. Our previous cross-sectional study revealed the age-dependent airway occupation ratio of Ad and Tn in Japanese individuals. We conducted a longitudinal observational study of the Ad and Tn sizes in Japanese individuals aged 6-20 years. Ninety individuals were retrospectively enrolled. The average and standard deviation of the sizes was calculated in 5 age-based groups.

Effects of pepsin and pepstatin on reflux tonsil hypertrophy in vitro.

There is evidence that pepsin can aggravate tonsil hypertrophy. Pepstatin is a potent inhibitor of pepsin activity and could protect patients against reflux tonsil hypertrophy by inhibiting pepsin. We examined the effects of pepstatin on the development of tonsil hypertrophy to investigate pepsin's role in the pathogenesis of tonsil lesions. We investigated whether pepstatin suppresses pepsin-mediated lymphocyte proliferation in tonsil hypertrophy. Forty-nine children with tonsil hypertrophy and twenty-two adults with tonsillitis were recruited to the study prior to surgery. Tonsil tissue from each patient was harvested and assessed for changes in the number of lymphocytes and macrophages in the presence of pepsin and pepstatin. We found that the proportions of CD4- and CD14-positive cells were significantly lower (p < 0.05), but that the proportions of CD19- and CD68-positive cells were significantly higher (p < 0.05), in children than in adults. There were significantly more CD4-positive cells after pepsin treatment, but these numbers were reduced by pepstatin. The levels of both interleukin-2 (IL-2) and interferon gamma (IFN-γ) increased significantly in response to pepsin, but were reduced when pepsin was inhibited by pepstatin. The level of IL-10 is reduced in pepsin-treated CD4 cells and the level is restored by pepstatin. IL-2 blocking reduced the increased CD4 cell number by pepsin. But, an additive or a synergic effect is not founded in combined with IL-2 blocking and pepstatin. Pepsin-positive cells did not co-localize with CD20 and CD45 cells, but they were found surrounding CD20- and CD45-positive hypertrophic tonsil cells. Pepsin-positive cells co-localized with CD68-positive cells. It is probable that pepsin from extraesophageal reflux aggravates tonsil hypertrophy and pepstatin exerts a protective effect by inhibiting pepsin activity.

Histological studies on the development of porcine tonsils after birth.

Tonsils form the topographically first immune barrier of an organism against the invasion of pathogens. We used histology to study the development of tonsils of pigs after birth. At birth, the tonsils consist of diffuse lymphoid tissue without any lymphoid follicle aggregations. At the age of 7 days, lymphoid follicles appeared in the soft palate tonsil. The lymphoid layer of the nasopharyngeal tonsil, soft palate tonsil, and lingual tonsil became thicker, and lymphoid follicles in the lamina propria were clearly visible at the age of 21 days. Secondary lymphoid follicles were present in the nasopharyngeal tonsil at the age of 50 days, and in the soft palate tonsil at the age of 120 days. Dendritic cells (DCs), CD3+ T cells and IgA+ B cells in the soft palate tonsil, nasopharyngeal tonsil and lingual tonsil increased continuously, especially during the first 21 days. The results suggested that tonsils have an important role in local immune defense against invading antigens after birth and will be beneficial for understanding the mechanisms of immunity in these animals after nasal and oral vaccination.

The relationship between allergic status and adenotonsillar regrowth: a retrospective research on children after adenotonsillectomy.

Adenotonsillar regrowth in children after adenotonsillectomy (T&A) for obstructive sleep apnea (OSA) is often seen in clinical treatment, however, the relationship between allergic disease and adenotonsillar regrowth remains unclear. In this retrospective study, children were assigned to either the recurrence or control group, and subdivided by age at operation. Among children over 36 months, those in the recurrence group had more allergic disease and higher IgE, IL-4, and IL-5 levels than the same-aged children in control group. The Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) scores for nasal symptoms and activity were higher in children older than 36 months in recurrence group. The results of immunohistochemistry and immunofluorescence showed that FoxP3+ cells (Tregs) were less, while GATA3+ cells (Th2 cells) were more in recurrence group for all ages. Allergic status and low levels of FoxP3 were proved as independent risk factors for adenotonsillar regrowth by multivariate logistic regression. These results indicate that allergic disease is a risk factor for adenotonsillar regrowth in children following T&A for OSA, and this risk increases with age. The decreased level of Tregs and subsequent changes in immune function play an important role in the pathogenesis of adenotonsillar regrowth.

Risk of reoperation after tonsillotomy versus tonsillectomy: a population-based cohort study.

Tonsil surgery to address upper airway obstruction in children can be performed either as a tonsillectomy (TE) or as a tonsillotomy/intracapsular/partial tonsillectomy (TT). The advantage of TT is a decreased risk of postoperative morbidity. The disadvantage is the risk of tonsil regrowth with recurrence of symptoms and/or problems with future tonsil infections, which may demand a reoperation of the tonsils. The aim of this study is to compare the risk of reoperation of the tonsils following TE and TT in children with tonsil-related upper airway obstruction. This is a retrospective register-based cohort study of the Swedish National Patient Register. All children aged 1-12 years who underwent TE or TT from 2007 to 2012 for the main indication of upper airway obstruction were included in the study. The unique Personal Identity numbers were used to follow patients over time in the register and identify additional tonsil surgery. A total of 27,535 patients were included in the study, contributing 76,054 person-years of follow-up. A total of 684 patients (2.5 %) underwent a second tonsil surgery during follow-up. The incidences of reoperation were 1.94 per 1000 person-years in the TE group and 16.34 per 1000 person-years in the TT group. The risk for reoperation was seven times higher (HR 7.16) after TT compared to TE. Younger age was significantly associated with reoperation for both TE and TT and the difference in risk between TE and TT gradually decreased with time. The most common indication for reoperation after both TE and TT was "Upper airway obstruction".

Mapping the Diversity of Follicular Helper T Cells in Human Blood and Tonsils Using High-Dimensional Mass Cytometry Analysis.

Single-cell analysis technologies such as mass cytometry allow for measurements of cellular heterogeneity with unprecedented dimensionality. Here, we applied dimensionality reduction and automated clustering methods on human T helper (T(H)) cells derived from peripheral blood and tonsils, which showed differential cell composition and extensive T(H) cell heterogeneity. Notably, this analysis revealed numerous subtypes of follicular helper T (T(FH)) cells that followed a continuum spanning both blood and tonsils. Furthermore, we identified tonsillar CXCR5(lo)PD-1(lo)CCR7(lo) T(FH) cells expressing interferon-γ (IFN-γ), interleukin-17 (IL-17), or Foxp3, indicating that T(FH) cells exhibit diverse functional capacities within extrafollicular stages. Regression analysis demonstrated that CXCR5(lo)PD-1(-) and CXCR5(lo)PD-1(lo) cells accumulate during childhood in secondary lymphoid organs, supporting previous findings that these subsets represent memory T(FH) cells. This study provides an in-depth comparison of human blood and tonsillar T(FH) cells and outlines a general approach for subset discovery and hypothesizing of cellular progressions.

Age-dependent changes in the size of adenotonsillar tissue in childhood: implications for sleep-disordered breathing.

OBJECTIVE: To analyze age-associated changes in linear and cross-sectional area (CSA) measurements of adenoid, tonsils, and pharyngeal lumen. STUDY DESIGN: Measurements were completed in head magnetic resonance imaging examinations performed for diagnostic purposes. Linear and nonlinear regression models were applied to describe the effect of age on the size of soft tissues and upper airway. RESULTS: Magnetic resonance imaging data were analyzed in 149 children without snoring (aged 0-15.9 years) and in 33 children with snoring (aged 1.6-15 years). In the children without snoring, adenoid size increased during the first 7-8 years of life and then decreased gradually [% (adenoid oblique width/mental spine-clivus length) = 11.38 + 1.52 (age) - 0.11 (age)(2), R(2) = 0.22, P < .01; adenoid CSA = 90.75 + 41.93 (age) - 2.47 (age)(2); R(2) = 0.50; P < .01]. Nasopharyngeal airway CSA increased slowly up to age 8 years and rapidly thereafter. Similar patterns were noted for the tonsils and oropharyngeal airway. In contrast, in children with snoring, adenoid and tonsils were large irrespective of age, and nasopharyngeal airway size increased slowly with age. CONCLUSIONS: In children without snoring, growing adenotonsillar tissue narrows the upper airway lumen to variable degrees only during the first 8 years of life. In contrast, in children with snoring, appreciable pharyngeal lymphoid tissue enlargement is present during the preschool years and persists beyond the eighth birthday.

Age-related tonsillar regrowth in children undergoing powered intracapsular tonsillectomy.

OBJECTIVES: To review our experience with intracapsular tonsillectomy using powered instrumentation (PIT) in the management of tonsillar hypertrophy. DESIGN: Retrospective database review of pediatric patients undergoing PIT. METHODS: The medical records of 636 patients under 11 years of age who underwent PIT performed by the senior author (RFW), predominantly for obstructive sleep disturbance, were reviewed. Data were subsequently analyzed from 559 of these patients for clinical evidence of tonsillar regrowth, post-operative tonsillar hemorrhage, and post-operative dehydration due to pain. Specific information for possible correlation of age at the time of surgery and any increased rate of regrowth was primarily examined. RESULTS: There were a total of 33 patients who had clinical evidence of regrowth. Children less than 5 years of age had 5 times the incidence of regrowth (p<0.001). Out of the group that exhibited regrowth, 5 patients exhibited evidence of recurrent upper airway obstruction and underwent a complete tonsillectomy. The age of this complete tonsillectomy group ranged from 1.1 to 2.7 years. Out of all patients undergoing PIT, there was 1 incident of delayed post-operative dehydration due to emesis but not due to pain. There were 2 incidents of delayed post-operative tonsillar bleeds. All three complications were self-limited and did not require re-hospitalization. CONCLUSIONS: PIT is a safe procedure with a small risk of tonsillar regrowth being age related. The incidence of postoperative complications following PIT is relatively low (0.54%).

Why do palatine tonsils grow back after partial tonsillectomy in children?

Within the last decade, adenoidectomy with partial tonsillectomy has been revived in children with obstructive sleep-disordered breathing caused by adenotonsillar hyperplasia, generating debate about remaining tonsillar tissue regrowth. The study examined potential risk factors of the regrowth. Prospective, nonrandomised, case series feasibility study of children meeting the criteria for palatine tonsils regrowth after partial tonsillectomy performed in patients with obstructive sleep-related breathing disorder was carried out. Out of 793 operated children, 294 after adenoidectomy and 373 after adenotonsillotomy were followed up for 4 years in 12-month intervals. In 27 children after adenotonsillotomy, regrowth of tonsillar tissue was observed. In 22 individuals after adenoidectomy alone, hyperplasia of palatine tonsils was noted. The children had bacterial cultures of pharyngeal smears and blood samples tested for anti-streptolysin O, C-reactive protein and total IgE. Caregivers completed a questionnaire reporting on: their child's breathing after surgery; frequency, severity and treatment of upper respiratory tract infections; diet; family history of adenoidal and/or tonsillar hyperplasia; and history of allergy. As controls, 272 participants after adenoidectomy alone and 346 after adenotonsillotomy were examined. The amount of sugar in the diet and the incidence of upper respiratory tract infections after surgery differed between the groups of patients and controls. Other differences were insignificant. The tonsillar tissue remaining after partial tonsillectomy in children has a remarkable tendency to grow back, related to a diet abundant in sugar and numerous upper respiratory tract infections. Tonsillar regrowth was age related and occurred most frequently in individuals older than 7 years.

Changes in the properties of secretory granules in the palatine gland acinar cells of the postnatally developing rat.

This study was designed to examine whether or not phospholipid is contained in the secretory granules of the rat palatine gland acinar cells, and if present, to examine the movements of phospholipid in the secretory granules during postnatal development. The palatine glands of male Wistar rats aged 0 to 56 days were used. Acid-hematin staining showed a few positive acinar cells with a faint reaction in the acini on day 0, numerous positive cells with an intense reaction on day 7, a weakening reaction in the cells on day 14, and almost no reactivity on day 35 and after. In contrast, alcian blue staining showed acinar cells with a weak reaction on day 7, a gradual increase in the reaction from day 14, and the presence of many cells with an intense reaction on day 28 and after. Electron probe microanalysis (EPMA) revealed a higher density of phosphorus in samples on day 7 than on day 56. These findings suggest that developing rat palatine gland acinar cells contain phospholipid in the secretory granules, being particularly more conspicuous around postnatal day 7, but that the amount of phospholipid decreases as the cells change to mature mucous cells.

Histological analysis of palatopharyngeal muscle from children with snoring and obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is an upper airway obstruction that occurs during the sleep. One of the suggested mechanisms involved in this process is a neuromuscular abnormality of the palatal muscles. Whether children with OSAS develop into OSAS adults, or children and adult OSAS are two distinct disorders occurring at different ages are questions to be answered. Here, we made the histological analysis of palatophryngeal muscle in 34 oral-breathing children of both genders, aged 5-12 years old, with hypertrophic tonsils and adenoids. According to the polysomnographic study the participants were divided into children without sleeping disorders (group I) and children with primary snoring (group II) or apnea (group III). The main histological findings were fiber size variability in 70% cases from groups II and III and in 71% from group I; perimysial connective tissue infiltration in 48% children from groups II and III and in 71% from group I; intracytoplasmatic mitochondrial proliferation in 63% cases from groups II and III and in 57% cases from group I. Muscle necrosis was only observed in one case, in association with subglandular inflammation. Others findings observed in all groups included fibers with internal architecture alteration, such as moth-eaten and lobulated fibers, type 2 fiber predominance, and small areas of fiber type grouping. The presence of similar histological findings in the palatopharyngeal muscle in children with primary snoring or apnea but also in children without sleeping disorders indicate that such changes could be a normal histological feature of this muscle rather than a neurogenic or myopathic pathology.

Histological studies on the ontogeny of bovine palatine and pharyngeal tonsil: germinal center formation, IgG, and IgA mRNA expression.

The development and distribution of lymphocyte subsets in calf palatine and pharyngeal tonsil were examined. During prenatal development, B cells were distributed in the subepithelial area, and T cells and MHC class II(+) cells were found in the deep layer of B-cell area, respectively, in both tonsils. At neonatal stage, lymphoid follicle containing a few CD4(+) cells have been formed in both tonsils. IgG(+) and IgA(+) cells were found in the parafollicular and epithelial area. At 3 months old, many germinal centers were recognized in both tonsils. CD4(+) cells and IgG mRNA expression were detected in light zone of germinal centers. Many IgG, and IgA mRNA expressions also could be detected in the parafollicular and subepithelial area of both tonsils. The data suggest that both tonsils have an important role of local immune defense against invading antigen after birth. The comparison of the histological characteristics of tonsil and Peyer's patch during ontogeny is also discussed.

Development of the palatine tonsil in conventional and germ-free piglets.

Palatine tonsils, like the Peyer's patches, are considered to be major inductive sites for the mucosa-associated lymphoid tissue (MALT), providing sampling and effector functions for the upper respiratory tract. Consistent with this, they have the architecture required of a classic inductive site (B-cell follicles, immunoglobulin class switching and the presence of naïve and memory T-cells). Here we show that much of this architecture develops after birth in the neonatal piglet, the numbers of T-cells, B-cells and accessory cells increasing with age. Conventional piglets also had higher levels of activated and memory T-cell subsets than germ-free piglets, consistent with development occurring as a result of microbial stimulus. The results suggest that the microbial environment influences the development of the tonsil immunological architecture. Given the role of the tonsil in induction of mucosal responses, this raises questions as to the effectiveness of the tonsil in dealing with colonising organisms in the neonate.

Histone mRNA in situ hybridization in assessing proliferative activity of normal and malignant cells.

Proliferative capacity is an important determinant of tumour biological behaviour. For research and diagnostic purposes, immunohistochemical techniques are usually applied in the assessment of tissue proliferative status. An interesting alternative for these studies is a detection of histone mRNA. As the synthesis of histones is tightly coupled with DNA replication during S-phase of the cell cycle, histone mRNA level is a specific marker of S-phase cells. Furthermore, a short-lived transcript guarantees accurate estimation of S-phase cell pool at the moment of tissue fixation. The progress in molecular biology techniques during the last decade made possible the use of in situ hybridization, especially its non-radioactive version, in routine laboratory services. This technique can be successfully applied to detection of histone mRNA in routinely processed tissues. Advantages and limitations of such approach in tumour proliferation studies are discussed.

Developmental study of the anal tonsil in the laboratory shrew, Suncus murinus.

The laboratory shrew, Suncus murinus, which lacks such gut associated lymph organs as the appendix and Peyer's plates, was recently demonstrated (Kubo and Isomura, 1996) to possess a pair of anal tonsils at the end of its rectum. The present paper deals with the development of this lymphoid organ as observed by light and electron microscopy. The anal tonsil was characterized by the initial postnatal development. On neonatal Day 1, a pair of epithelial crypts formed at the dorsal boundary between the anus and the ostium urogenitoanale. On Day 2 after birth, lymphocytes began to accumulate in the subepithelial mesenchymal tissue under the crypt. From Day 3 on, the lymphocytes increased to form a lymph nodule, from which, on Day 5, some lymphocytes began to penetrate into the crypt epithelium. The crypt and the nodule were fused together between Days 6 and 8. A germinal center-like structure was observed on Day 20 after birth. Around Day 40, the invading cells comprised cellular units consisting of large and small lymphocytes and plasma cells. High endothelial venules were observed in the parafollicular area at this time. These findings indicate that the anal tonsil originates from an accumulation of lymphocytes in the mesenchymal tissue close to a particular epithelium of the crypt, presumably in response to antigens in foods; the tonsilar structure is then gradually completed by fusion of the lymphoid and epithelial elements. This paper further reports on an electron microscope finding on Day 8 where the anal tonsillar crypt epithelium was seen to contain some basal-granulated cells of the open type.