Dense Plasma Cell Infiltration Research Articles

Lymphocytic Interstitial Pneumonia with Varied Association: Case Series

Lymphocytic interstitial pneumonia (LIP) is an unusual variant of interstitial lung disease with unknown incidence and prevalence. It is often seen in patients with autoimmune diseases and in immune-compromised individuals, and is associated with specific infections; rarely, it is idiopathic. Idiopathic LIP has a male preponderance, while the secondary form is more common in females. It is characterized by dense infiltration of polyclonal lymphocytes, plasma cells, and histiocytes in the interstitial and alveolar spaces. Early diagnosis and treatment initiation are crucial for a favorable prognosis. Here, we present four cases of LIP with variable associations, emphasizing the importance of clinical examination, imaging, and, whenever needed, a transbronchial lung biopsy for accurate diagnosis.

Challenges and solutions in plasma cell gingivitis: A clinical case analysis

Plasma cell gingivitis (PCG) is an uncommon benign gingival condition characterized by sharply defined erythematous and oedematous gingival lesions, often extending to the mucogingival junction. This hypersensitivity reaction presents as diffuse, papillary gingival inflammation, prone to bleeding upon minimal trauma. Histologically, PCG manifests as a dense infiltration of normal plasma cells within collagenous stroma, typically localized to the free and attached gingiva. The primary management approach involves identification and avoidance of the allergen source, alongside nonsurgical periodontal therapy. We report a 26-years-old female patient diagnosed clinically as plasma cell gingivitis and confirmed histologically. Surgical treatment along with pharmacological interventions resulted in complete resolution of symptoms. This case underscores the importance of comprehensive evaluation and tailored treatment approaches in managing plasma cell gingivitis.

Plasma cell gingivitis – An enigma

Plasma cell gingivitis (PCG) is a rare benign inflammatory disorder affecting the gingiva characterized by dense infiltration of plasma cells into the sub-epithelial connective tissue. It is considered a hypersensitivity reaction to various allergens; thus, the first step in management is to remove the causative factor. We are reporting a case of a 73-year-old male who presented with redness and swelling of upper gums, which bleeds easily on probing. The final diagnosis of PCG was confirmed by histology and immunochemistry. In this article, we report a rare case of PCG.

Analysis of clinicopathological characteristics of IgG4-related sialadenitis

Objective: To analyze the clinicopathological characteristics of IgG4-related sialadenitis (IgG4-RS). Methods: A total of 40 cases diagnosed with IgG4-RS were collected from the Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2019 to December 2022. Among them, there were 26 males and 14 females. The age range was 29-77 years old [(59.4±11.8) years old], with 23 patients being older than 60 years. The lesion site, imaging manifestations, histopathological features, serological test and treatment information of patients were collected. The expression of IgG4 and IgG proteins was detected by immunohistochemistry. Results: Submandibular region swelling was the most common initial symptom of IgG4-RS (38/40, 95.0%). All the patients having serum IgG4 levels> 1.35 g/L. Serum IgG4 levels were significantly increased in patients aged>60 years (Z=-2.45, P=0.014) and those involving multiple glands (Z=-2.04, P=0.042). Thirty six cases received major salivary gland biopsy, and all the cases showed dense lymphocyte and plasma cell infiltration. Lymphoid follicle, storiform fibrosis and obliterative phlebitis were seen in 88.9% (32/36), 63.9% (23/36), 30.6% (11/36) of the cases, respectively. Twenty one cases received labial salivary gland biopsy, 66.7% (14/21) showed lymphocyte and plasma cell infiltration, 19.0% (4/21) had lymphoid follicle structures, and 33.3% (7/21) showed no obvious histological abnormalities. No signs of fibrosis or obliterative phlebitis were observed in all labial salivary gland biopsies. And 95.0% (38/40) of cases had IgG4 positive plasma cell>10/HPF, 82.5% (33/40) of cases had IgG4/IgG positive plasma cell ratio>40%. All the patients had a decrease in serum IgG4 levels after glucocorticoid treatment, but only 21.4% (6/28) of cases had reduced to normal levels (≤1.35 g/L), and there were still significant fluctuations in serum IgG4 levels thereafter. Conclusions: IgG4-RS has a predilection for middle-aged and elderly male patients, and serum IgG4 levels are significantly related to the patient's age and whether multiple glands are involved. Labial salivary gland biopsy cannot replace submandibular gland for histopathological evaluation. It is a common phenomenon that serum IgG4 levels cannot restored to normal levels after glucocorticoid treatment. This study provides certain assistance for clinical and pathological diagnosis of IgG4-RS. This study is beneficial for further understanding IgG4-RS and improving the clinical and pathological diagnosis of the disease.

Plasma Cell Gingivitis and Its Mimics.

Plasma cell gingivitis (PCG) is an inflammatory condition that affects the gingival mucosa of the oral cavity. It is characterized by polyclonal dense plasma cell infiltrate in the connective tissue. Lesions do not respond to prophylactic treatment. Etiology is most likely hypersensitivity to certain antigens (eg, toothpastes, oral rinses, chewing gums, spices). Differential diagnosis of PCG includes reactive, granulomatous, and neoplastic lesions. The diagnostic workup is based on patient's history and the clinicopathologic correlation to rule out mimics of PCG. Dermatologic patch test may be indicated in chronic conditions to identify the allergen.

The histopathological characteristics of peri-implantitis

Peri-implantitis (PI) has been defined as an inflammatory lesion of the mucosa surrounding an endosseous implant and with progressive loss of supporting peri-implant bones. In recent years, histopathological differences between PI and periodontitis of natural teeth had been described in animal experiments and a certain number of human experiments. In this paper, we review the histopathological differences between PI and periodontitis reported in the existing literature and try to find the differences in the occurrence and progression of these two diseases. Overall, inflammatory cell infiltrate (ICT) is more extensive in PI than in periodontitis, extending to the alveolar ridge, with dense infiltration of plasma cells, lymphocytes, macrophages, polymorphonuclear leukocytes and a greater number of osteoclasts in the connective tissue, but with less vascular density within ICT than in periodontitis. In addition, foreign bodies are found in PI lesions. The histopathological differences between the two diseases in terms of inflammatory infiltration, vascularity, bone loss, and foreign bodies could partially explain the more rapid progression of PI than periodontitis, suggesting that PI should be taken seriously by physicians. Early diagnosis and treatment are essential to control the progression of PI. In addition, targeted therapy against specific inflammatory cells may become a new direction for PI treatment; reducing titanium particles released into peri-implant tissue by friction or electrochemical corrosion may help to prevent PI.

IgG4-related hypophysitis: A monocentric experience from North India.

Immunoglobulin (Ig)G4-related disease is a systemic fibroinflammatory disease characterized by dense infiltration of IgG4-positive plasma cells in the affected tissue(s) with or without elevated plasma levels of IgG4. Hypophysitis itself is a very rare disease with reported prevalence in the operative specimens are around 0.2-0.88%. IgG4-related hypophysitis (IgG4-RH) may account for a substantial percentage of cases previously regarded as idiopathic hypophysitis. This study is a registry-based, retrospective, and cohort study from a tertiary care hospital in North India. The medical records and clinical data of biopsy-proven and suspected IgG4-RH patients registered were retrospectively analyzed. Treatment outcome of cases was also explored during this analysis. Two thousand and six sellar area space-occupying lesions have been operated-on since 2006, among them only four patients had IgG4-RH on histopathological specimen. One case was diagnosed on clinical suspicion. Mean age of the patients was 31.8 ± 6.32 years. Most frequent presenting complaint was headaches. Extracranial manifestations were present in four patients. The most common pituitary dysfunction was cortisol deficiency. 18 F-fluorodeoxyglucose positron emission tomography (18F FDG PET) was helpful in three cases for diagnosis of hypophysitis and other organ involvement. Classical histological findings with storiform fibrosis, obliterative phlebitis seen in two cases, and IgG4-positive plasma cell infiltration were positive in four cases. Surgery was the primary modality of treatment in all four cases. Only one patient received steroids as a primary therapeutic modality. IgG4-RH is rare. High index of suspicion is required to diagnosis the case precisely. FDG PET is helpful in diagnosing hypophysitis and extrapituitary lesions.

S2001 Chronic Norovirus Infection in a Double Solid Organ Transplant Patient

Introduction: Infectious diarrhea is a common complication in the postoperative course of a solid organ transplant (SOT) recipient. While self-limiting in immunocompetent patients, transplant patients on long-term immunosuppression can have severe, prolonged disease with significant morbidity. We present a case of chronic diarrhea due to recurrent norovirus infection in a double SOT patient to encourage early recognition. Case Description/Methods: A 61-year-old male presented with 35-pound weight loss despite a good appetite and large-volume watery diarrhea intermittently for 2 years. He had a liver-kidney transplant 14 years prior secondary to cryptogenic cirrhosis and renal cell carcinoma. Immunosuppression consisted of prednisone, tacrolimus, and mycophenolate mofetil (MMF). Stool PCR was positive for norovirus and negative for other viruses, bacteria, and parasites. His MMF dose was reduced with no benefit. He was discharged with supportive care with initial improvement in the diarrhea but returned to the hospital 4 other times with worsening diarrhea and weight loss. Infectious workup was persistently positive for norovirus. Bi-directional endoscopy with biopsies revealed colonic mucosa with rare epithelial apoptosis, chronic duodenitis, and increased intraepithelial lymphocytosis in the duodenum and ileum consistent with chronic norovirus (Figure). The full diagnostic workup is detailed in Table 1. He was managed conservatively during each hospitalization with fluids and antimotility agents and recently discharged home with plans to start nitazoxanide outpatient. Discussion: Norovirus infection among SOT patients can lead to severe and symptomatic chronic infection. Patients can develop dehydration, transplant rejection, and malnutrition making them higher risk for hospitalizations and death. It is unclear why some immunocompromised patients recover spontaneously while others demonstrate a protracted course but supportive care is the mainstay of therapy. Limited case series have shown nitazoxanide to be effective in treating SOT patients with chronic norovirus infection. However, nitazoxanide needs to be continued until stool RNA studies become negative. This case highlights the importance of considering chronic norovirus when a SOT patient presents with chronic diarrhea and weight loss. Early initiation of supportive care and nutrition consultation are imperative in reducing morbidity in these patients. Nitazoxanide can be effective in patients that are refractory to supportive therapy.Figure 1.: Duodenal biopsy (A): Focal intraepithelial lymphocytosis and lamina propria plasma cell infiltrates. Terminal ileum biopsies (B,C): Focal intraepithelial lymphocytosis and lamina propria plasma cell infiltrates (B); popcorn-like epithelial apoptosis (C). Table 1. - Diagnostic Workup Test/Procedure Result Creatinine, serum 2.1 mg/dl (baseline 1 mg/dl) Stool PCR -Positive for norovirus-Negative for Clostridium difficile toxins, Salmonella, Shigella, Yersinia, and Campylobacter Osmolality, feces 420 mOsm/kg Fecal fat Abnormal Duodenal biopsy -Mucosa with intraepithelial lymphocytosis, dense plasma cell infiltrates in the lamina propria, and rare apoptotic bodies-Negative for CMV, EBV, HSV Stomach biopsy -Gastric antral and oxyntic gland mucosa with chronic inactive gastritis-Negative for H. pylori Right colon biopsy Rare epithelial apoptosis Left colon biopsy Rare epithelial apoptosis Terminal ileum biopsy Mucosa with intraepithelial lymphocytosis, dense plasma cell infiltrates in lamina propria, and rare apoptotic bodies

S3588 Eosinophilic Gastroenteritis and Colitis After Intragastric Balloon Placement

Introduction: Eosinophilic gastrointestinal diseases (EGIDs) are a group of rare disorders characterized by infiltration of eosinophils in the gastrointestinal tract. Hypersensitivity to food or environmental allergens is believed to play a pivotal role in the pathogenesis. Intragastric balloon (IGB) has been demonstrated as an effective and safe therapy for weight loss. Interestingly, a previous report described development of eosinophilic esophagitis (EoE) following IGB placement, suggesting a possible association between IGB and EGIDs. Case Description/Methods: A 61-year-old male underwent endoscopic placement of an Orbera® intragastric balloon for weight reduction. Forty days later, he presented with a 3-day history of watery and non-bloody diarrhea, abdominal pain, and nausea. Labs were notable for severe peripheral eosinophilia over 15,000/mL. Extensive infectious workup were unremarkable. His IGB was removed as he had reached his goal weight. Then, he underwent esophagogastroduodenoscopy and flexible sigmoidoscopy with biopsy. Endoscopic exam was notable for diffuse erythema in the stomach and duodenum, and congestion in the colon. Histologically, dense inflammatory infiltration of eosinophils and plasma cells in the lamina propria was found in the stomach, duodenum, and colon. After removal of the IGB, his symptoms and peripheral eosinophilia improved rapidly, and were resolved completely within 1 month without need for immunomodulatory therapies or diet modifications. Discussion: We describe a case of eosinophilic gastroenteritis and colitis with severe peripheral eosinophilia following IGB placement, in whom rapid resolution occurred after IGB removal without additional therapies. To our knowledge, this is the first case report that suggests a possible association between IGB and non-EoE EGIDs, which warrants clinicians' awareness and further studies.

33521 Two cases of oral baricitinib associated papular eruption on face

Background: Janus kinase (JAK) inhibitors reduce inflammation by interrupting JAK-STAT pathway and are used for various disease. However, cutaneous adverse effects including reactivation of herpes simplex virus, herpes zoster, disseminated molluscum contagiosum, and acneiform eruptions were reported. In addition, few cases of granulomatous inflammation after JAK inhibitor use have been reported recently. Methods: Patient 1, a 40-year-old woman, presented with erythematous papules on periorbital and perioral area for 13 months. She had been taking prednisolone and hydroxychloroquine for rheumatoid arthritis (RA) for 1 year, but symptoms were not controlled. Thus, oral baricitinib was administered. After 2 months, facial lesions appeared. Patient 2, a 64-year-old woman, presented with erythematous papules on face developed 2 weeks ago. She has been taking baricitinib for RA because of inadequate response to methotrexate. Facial eruption occurred 4 months after initiation of baricitinib. Results: For patient 1, histopathologic examination showed dense dermal infiltration of lymphocytes, histiocyte and few plasma cells, which implicated granulomatous dermatitis. Doxycycline and topical gentamycin/prednicarbate were given and the lesions showed response. Patient 2 showed improvement after treatment with doxycycline, topical metronidazole, and topical ivermectin. However, lesions aggravated 7 months after doxycycline cessation with continuous baricitinib use. Conclusion: Although JAK inhibitors are known to be effective for the treatment of granulomatous diseases like sarcoidosis, granulomatous drug eruption has been reported. In our cases, facial skin lesions appeared 2 and 4 months after starting baricitinib, respectively. Our cases imply that dermatologists should be aware of the potential association between JAK inhibitors and cutaneous eruption.

33521 Two cases of oral baricitinib associated papular eruption on face

Background: Janus kinase (JAK) inhibitors reduce inflammation by interrupting JAK-STAT pathway and are used for various disease. However, cutaneous adverse effects including reactivation of herpes simplex virus, herpes zoster, disseminated molluscum contagiosum, and acneiform eruptions were reported. In addition, few cases of granulomatous inflammation after JAK inhibitor use have been reported recently. Methods: Patient 1, a 40-year-old woman, presented with erythematous papules on periorbital and perioral area for 13 months. She had been taking prednisolone and hydroxychloroquine for rheumatoid arthritis (RA) for 1 year, but symptoms were not controlled. Thus, oral baricitinib was administered. After 2 months, facial lesions appeared. Patient 2, a 64-year-old woman, presented with erythematous papules on face developed 2 weeks ago. She has been taking baricitinib for RA because of inadequate response to methotrexate. Facial eruption occurred 4 months after initiation of baricitinib. Results: For patient 1, histopathologic examination showed dense dermal infiltration of lymphocytes, histiocyte and few plasma cells, which implicated granulomatous dermatitis. Doxycycline and topical gentamycin/prednicarbate were given and the lesions showed response. Patient 2 showed improvement after treatment with doxycycline, topical metronidazole, and topical ivermectin. However, lesions aggravated 7 months after doxycycline cessation with continuous baricitinib use. Conclusion: Although JAK inhibitors are known to be effective for the treatment of granulomatous diseases like sarcoidosis, granulomatous drug eruption has been reported. In our cases, facial skin lesions appeared 2 and 4 months after starting baricitinib, respectively. Our cases imply that dermatologists should be aware of the potential association between JAK inhibitors and cutaneous eruption.

LOWER LIP MELANOACANTHOMA MICROSCOPICALLY PRESENTING PLASMA CELL CHEILITIS–LIKE FEATURES

Oral melanoacanthoma is an uncommon benign pigmented lesion, microscopically presenting hyperplasia of spinous keratinocytes and dendritic melanocytes. Its pathogenesis remains uncertain, although the clinical behavior suggests a reactive origin. Oral melanoacanthoma affects mainly young adults and Blacks, with a strong female predilection. The most common oral sites are the buccal mucosa, lip, palate, and gingiva. Plasma cell cheilitis (PCC) is an inflammatory disorder of unknown etiology that affects the lips. The clinical presentation of PCC is variable, sometimes simulating malignancy, and microscopically characterized by a dense plasma cell infiltrate. Here, we present a 59-year-old Black male patient presenting blackish-colored lesions, associated with a reddish erosive area, on the lower lip, 1.5 years ago. Microscopy revealed melanoacanthoma associated with intense lymphoplasmacytic infiltrate, such as observed in PCC. If the current case represents a microscopic spectrum of melanoacanthoma or simultaneous presence of melanoacanthoma and PCC remains open to debate, however, we favor the former.

Enhanced oxidative phosphorylation of IgG plasma cells can contribute to hypoxia in the mucosa of active ulcerative colitis.

Mucosal hypoxia is detected in the mucosa of ulcerative colitis (UC), however the mechanism and the cause of hypoxia is not fully understood, while a dense infiltration of plasma cells is observed in the inflamed mucosa of UC. When differentiating from a B cell to a plasma cell, the energy metabolism dramatically shifts from glycolysis to oxidative phosphorylation, which results in a large amount of oxygen consumption of the plasma cell. We hypothesized that the plasma cell infiltration into the inflamed mucosa contributes to the mucosal hypoxia in UC in part. We examined the association between mucosal hypoxia and plasma cell infiltration in UC. More IgG plasma cells (but not IgA plasma cells) were distributed, and the nuclear and cell sizes were enlarged in hypoxic mucosa compared to normoxic mucosa in UC. Oxidative phosphorylation signature genes of these IgG plasma cells were markedly upregulated compared to those of other lymphoid cells infiltrating the lamina propria of inflamed mucosa of UC. Enlarged IgG plasma cells, which increase in number in the inflamed mucosa of UC, can be related to the hypoxic state of the inflamed mucosa of UC.

First report of rare persistence granulomatous extra respiratory Rhinoscleroma of oral pathology

Rhinoscleroma (RS) is a rare chronic specific progressive granulomatous disease of the upper airway and affect the nasal cavity, larynx, nasopharynx and may spread to the lower respiratory tract. Extra-respiratory involvement has rarely been described. A case report of extra-respiratory RS with oral manifestation in Egyptian female patient has been presented as a tumour extruded from mucosal lining of upper lip. She was living in crowded conditions with malnutrition and poor hygiene. On the first look, the lesion appeared to be carcinoma without any indication of infectious disease, and then patient was prepared for incisional biopsy. Upon clinicopathological evaluation, the diagnosis was made as RS in the granulomatous stage based on the presence of dense plasma cell infiltration with Mikulicz cells and Russell bodies. Long term oral ciprofloxacin 500 mg twice/day was started as a single treatment. By the end of six weeks antibiotic therapy, the large granulomatous mass reached the cicatricial stage, became very stiff fibrotic mass with sclerotic scar, markedly indurated & significantly decreased in size.This case shows the significant of through clinical examination and lab investigations to achieve correct diagnosis.

Melanoacanthoma, Plasma Cell Cheilitis and Langerhans Cell Hyperplasia on the Lower Lip: An Unusual Association and Immunohistochemical Analysis.

Oral melanoacanthoma is an uncommon reactive lesion, characterized by basal and prickle cell keratinocyte proliferation surrounded by pigment-laden dendritic melanocytes. Plasma cell cheilitis (PCC) is an inflammatory disorder of unknown aetiology, microscopically presenting a dense plasma cell infiltrate. Most PCC cases affect the lower lip. Langerhans cell hyperplasia (LCHyp), a non-neoplastic counterpart of the LC proliferations, has been reported in association with chronic inflammatory skin diseases. Here, we present an unusual association of melanoacanthoma, PCC and LCHyp on the lower lip in a 59-old-year male, expanding the clinicopathological spectrum of these uncommon lesions. The dendritic melanocytes were highlighted by Fontana-Masson stain and HMB-45, whereas S100, CD1a and CD207 evidenced numerous LCs. MUM1/IRF4, EMA, and CD138 highlighted sheets of polyclonal plasma cells, with an IgG4+/IgG+ ratio of 24%. FTA-ABS test for syphilis was negative.

Immunoglobulin G4-related Disease: A New Systemic Disease Emerging in Japan.

Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory disease characterized by organ enlargement and elevated serum IgG4 levels. In 2003, IgG4-RD was proposed as a distinct form of IgG4-related systemic disease based on a histopathological study involving patients with autoimmune pancreatitis. IgG4-RD occurs mainly in older men and can affect almost any organ simultaneously or metachronously. Pathophysiologically, IgG4-RD occurs when an autoantigen triggers an immune response characterized by Th2 predominance with increased production of cytokines, such as interleukin 4 (IL-4), IL-5, IL-10, IL-13, and tumor growth factor-β (TGF-β), in the affected organ. IL-10 and TGF-β produced by the increased number of regulatory T cells induce a switch from B cells to IgG4-producing plasma cells and fibrosis, respectively. The characteristic histological features consist of dense infiltration of lymphocytes and IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD is diagnosed based on a combination of clinical, serological, radiological, and histopathological findings. Differentiating IgG4-RD from malignant tumors or similar inflammatory diseases in the affected organs is important. The 2019 America College of Rheumatology/European League against Rheumatism classification criteria for IgG4-RD have high diagnostic sensitivity and specificity. IgG4-RD generally responds well to treatment with steroids, and a swift response is reassuring and provides further diagnostic confirmation. However, relapses are common during tapering or after cessation of steroids. In Japan, low-dose steroid maintenance therapy is usually given to prevent a relapse. B-cell depletion with rituximab is effective in patients resistant to or dependent on steroids. Most patients with IgG4-RD who receive steroid therapy show good short-term clinical, morphological, and functional outcomes. However, long-term outcomes, such as relapse, fibrosis development, and associated malignancies, have not been clearly defined. Therefore, novel treatment strategies, including rituximab, need to be tested in international randomized controlled clinical trials.

Gingival plasma cell granuloma: The importance of histological analysis

AbstractPlasma cell granuloma (PCG) is a mucosal condition characterised histologically by a dense aggregation of polyclonal plasma cells. There are limited reports in the literature of the condition affecting the oral mucosa and involvement of the gingival tissues is considered rare. The variable clinical presentation allows for a differential diagnosis of malignant conditions therefore awareness of the characteristics and distinctive histological features are important in avoiding misdiagnosis. We report a rare case of PCG presenting on the buccal gingivae of the posterior mandible, with concurrent mobility of the adjacent tooth, in a middle‐aged female. The clinical presentation of this lesion warranted urgent investigation, however, histological findings of a dense polyclonal plasma cell infiltrate revealed a benign PCG.

One liver, two samples and two diagnoses-An example of how multiple samples by laparoscopically guided liver biopsy can be decisive.

Laparoscopically-guided liver biopsy was performed to make the diagnosis in a 54-year old female patient with clinical and serological signs of both non-alcoholic fatty liver disease and autoimmune hepatitis (AIH). Figure A shows a sample from the right liver lobe (HE, 20x) with a blue-boxed area (Figure B) (HE, 100x) demonstrating a total of eight portal tracts. Macrovesicular steatosis of about 50% of hepatocytes and mild lymphocyte infiltration were detected.

Adamts18 Deficiency Causes Spontaneous SMG Fibrogenesis in Adult Mice

Chronic sclerosing sialadenitis of the submandibular gland (also known as Küttner tumor) is characterized by concomitant swelling of the submandibular glands secondary to strong lymphocytic infiltration and fibrosis. The pathogenesis of this disease has been unclear, but it is associated with immune disorders. ADAMTS18 is a member of the ADAMTS superfamily of extracellular proteinases. In this study, we showed that Adamts18 is highly expressed in submandibular salivary gland (SMG) during embryonic development and decreases but is retained in adult SMG tissue in mice. Adamts18 deficiency led to reduced cleft formation and epithelial branching in embryonic SMG before embryonic day 15.5 in mice. No significant histologic changes in the later stages of branching or the morphology of SMG were detected in Adamts18−/− mice. However, Adamts18 deficiency causes spontaneous SMG fibrogenesis and fibrosis in adult mice. At 8 wk of age, Adamts18−/− mice began to manifest the first signs of pathologic changes of mild fibrosis and CD11b+ cell infiltration in SMG tissues. At ≥8 mo, all male and female Adamts18−/− mice developed unilateral or bilateral SMG scleroma that is similar to patients with chronic sclerosing sialadenitis of the submandibular gland. Adamts18−/− mice also showed secretory dysfunction and severe dental caries. Histologically, SMG scleroma is characterized by progressive periductal fibrosis, acinar atrophy, irregular duct ectasis, and dense infiltration of IgG-positive plasma cells. A significant infiltration of CD4+ T lymphocytes and CD11b+ monocytes and macrophages was also detected in the SMG scleroma of Adamts18−/− mice. The levels of TGF-β1, IL-6, and IL-33 were significantly increased in Adamts18−/− SMGs, which induces chronic inflammation and myofibroblast activation, ultimately leading to fibrosis. This study indicates that Adamts18 regulates the early branching morphogenesis of embryonic SMG and plays a role in protecting from spontaneous SMG fibrogenesis via modulating local inflammation, autoimmune reaction, and myofibroblast activation in adult mice.

PLASMA CELL CHEILITIS TREATED WITH TOPICAL CORTICOSTEROID AND PHOTODYNAMIC THERAPY—CASE REPORT

<h3>Background</h3> Plasma cell cheilitis (PCC) is a rare, idiopathic, and benign inflammatory mucosal condition of unknown etiology, characterized by a dense plasma cell infiltrate within mucosa, principally affecting the lip. Treatment includes topical, intralesional, or systemic steroids; oral griseofulvin; liquid nitrogen; radiotherapy; and surgical excision. In most cases, PCC is resistant to topical treatment. <h3>Objective</h3> To report the treatment of PCC associated with topical corticosteroid with photodynamic therapy (PDT). <h3>Methods</h3> A 68-year-old woman was referred to the oral medicine ambulatory of the Clinical Hospital of São Paulo State University, Medical School, Botucatu, Brazil, for the appearance of sore wound with crust on the lower lip with progressive worsening without comorbidities, present for 5 months. Clinical examinations showed an ulcerated area with crust all over the lower lip. Diagnostic hypotheses were exfoliative cheilitis, cheilitis granulomatosa, and squamous cell carcinoma. Incisional biopsy revealed dense inflammatory infiltrate within the superficial corium, which consisted of sheets of plasma cells with occasional active blast cells. The treatment was topical 0.05% clobetasol gel twice a day with PDT twice/week (0.01% methylene blue topical for 3 minutes; irradiation was punctual by contact, energy 9 J, 660 nm, 100 mW, per point in 2 points until complete healing). <h3>Results</h3> The lesions were regressing with decreased pain. Total healing occurred in 3 months. <h3>Conclusions</h3> The association of topical corticosteroid with PDT is an alternative for the treatment of PCC.