Comprehensive Genomic and Transcriptomic Analysis of Sclerosing Pneumocytoma.

Sclerosing pneumocytoma is a rare and distinct lung neoplasm whose histogenesis and molecular alterations are the subject of ongoing research. Our recent study revealed that AKT1 internal tandem duplications (ITD), point mutations, and short indels were present in almost all tested sclerosing pneumocytomas, suggesting that AKT1 mutations are a major driving oncogenic event in this tumor. Although the pathogenic role of AKT1 point mutations is well established, the significance of AKT1 ITD in oncogenesis remains largely unexplored. We conducted comprehensive genomic and transcriptomic analyses of sclerosing pneumocytoma to address this knowledge gap. RNA-sequencing data from 23 tumors and whole-exome sequencing data from 44 tumors were used to obtain insights into their genetic and transcriptomic profiles. Our analysis revealed a high degree of genetic and transcriptomic similarity between tumors carrying AKT1 ITD and those with AKT1 point mutations. Mutational signature analysis revealed COSMIC signatures 1 and 5 as the prevailing signatures of sclerosing pneumocytoma, associated with the spontaneous deamination of 5-methylcytosine and an unknown etiology, respectively. RNA-sequencing data analysis revealed that the sclerosing pneumocytoma gene expression profile is characterized by activation of the PI3K/AKT/mTOR pathway, which exhibits significant similarity between tumors harboring AKT1 ITD and those with AKT1 point mutations. Notably, an upregulation of SOX9, a transcription factor known for its involvement in fetal lung development, was observed in sclerosing pneumocytoma. Specifically, SOX9 expression was prominent in the round cell component, whereas it was relatively lower in the surface cell component of the tumor. To the best of our knowledge, this is the first comprehensive investigation of the genomic and transcriptomic characteristics of sclerosing pneumocytoma. Results of the present study provide insights into the molecular attributes of sclerosing pneumocytoma and a basis for future studies of this enigmatic tumor.

Characteristics of Metastatic and Nonmetastatic Pulmonary Sclerosing Pneumocytomas: A Clinicopathological Study of 68 Cases and 15 Reported Metastatic Cases.

To characterize the clinicopathologic features of pulmonary sclerosing pneumocytoma (PSP) and compare these features between the tumors with and without metastasis, 68 cases of PSP (1/68 [1.47%] with metastasis) diagnosed from 2009-2022 in our hospital and 15 previously reported metastasizing cases were studied. There were 54 female patients and 14 male patients, with age ranging from 17 to 72 years and tumor size ranging from 0.1 to 5.5 cm (mean, 1.75 cm). In all, 85.4% of the cases presented with ≥2 patterns, including papillary, sclerotic, solid, and hemorrhagic. Thyroid transcription factor 1, epithelial membrane antigen, CKpan, and CK7 were expressed in surface cells in 100% of the cases and napsin A was expressed in 90% of the cases. Stromal cell expression of these markers occurred in 100%, 93.9%, 13.5%, 13.8%, and 0% of the cases, respectively. Of the 16 PSP cases with metastasis, 8 were female patients and 7 were male patients, with age ranging from 14 to 73 years. The tumor size ranged from 2.5 to 12 cm (mean, 4.85 cm). Forty-five of the cases were negative for BRAF V600E immunostaining and 6 were focally weak positive, in which fluorescent PCR tests showed no detectable mutations. There were significant differences in gender, age, and tumor size between PSP cases with and without metastasis. No BRAF V600E mutation was found in patients with PSP. AKT1 p.E17K mutations were detected in both the primary lung tumor and the lymph node metastatic tumor of our PSP case with lymph node metastasis. In conclusion, PSP is an uncommon pulmonary neoplasm with significant female predilection and has distinct morphologic and immunohistochemical characteristics. The BRAFV600E mutation was not detectable in patients with PSP and thus may not involve in its tumorigenesis. Most PSP tumors are benign, with a minority exhibiting potential for metastasis and malignant behavior.

Pulmonary sclerosing pneumocytoma containing spindle cells with sarcomatoid features: a case report with literature review.

BACKGROUND: Pulmonary sclerosing pneumocytoma (PSP) is an uncommon benign neoplasm originated from pneumocyte and PSP with malignant transformation is extremely rare. CASE PRESENTATION: We report a case of PSP of a 65-year-old male patient presented as a lobulated mass in the upper lobe of the left lung, in which part of the stromal round cells transformed to spindle cells with sarcomatoid features and showed no specific differentiation. The patient underwent partial lobectomy without further treatment. No recurrence and metastasis was found after eight month's follow up. CONCLUSIONS: To our knowledge, this is the first case of PSP with sarcomatoid malignant transformation devoid of differentiation. Our case adds the evidence in that a subset of PSP bear malignant potential and more studies are needed in order to determine the treatment and prognosis to such patients.

Pulmonary sclerosing pneumocytoma and mortality risk.

BACKGROUND: Surgical resection is usually recommended for the treatment of pulmonary sclerosing pneumocytoma (PSP). However, no comparative study has demonstrated that surgical resection leads to improved outcomes. We aimed to compare all-cause mortality between patients with PSP who underwent surgery or did not and those without PSP. METHODS: Participants aged ≥18 years who had pathologically diagnosed PSP between 2001 to 2018, at 3 hospitals were included. Randomly selected (up to 1:5) age-, sex-, and smoking status-matched controls without PSP who were randomly selected from those who underwent health checkups including chest CT were included. Mortality was compared using Kaplan-Meier estimates and Cox proportional hazards regression models. Literature review of studies reporting PSP was also conducted. RESULTS: This study included 107 patients with PSP (surgery:non-surgery, 80:27) and 520 matched controls. There were no cases of lymph node or distant metastasis, recurrence, or mortality from PSP. No significant difference in all-cause mortality risk was observed between the PSP surgery, PSP non-surgery, and non-PSP groups (log rank test P = 0.78) (PSP surgery vs. non-PSP: adjusted hazards ratio [aHR], 1.80; 95% confidence interval [CI], 0.22-14.6; PSP non-surgery vs. non-PSP: aHR, 0.77; 95% CI, 0.15-3.86; PSP surgery vs. PSP non-surgery: aHR, 2.35; 95% CI, 0.20-28.2). In the literature review, we identified 3469 patients with PSP from 355 studies. Only 1.33% of these patients reported metastasis, recurrence, or death. CONCLUSIONS: All-cause mortality did not differ between patients with PSP and those without, irrespective of undergoing surgery. Our study and the literature review suggest that PSP has less impact on increased mortality risk.

Sclerosing pneumocytoma with carcinoid tumorlets and neuroendocrine cell hyperplasia.

Sclerosing pneumocytoma is an uncommon pulmonary tumor which generally behaves benignly and occurs predominately in women. Rarely, it is associated with neuroendocrine proliferations such as hyperplasia, tumorlets and carcinoid tumors, which may be observed in relation to the tumor or in the distant lung parenchyma; the mechanism underlying this neuroendocrine differentiation is not clear. We present a case of a 33 year-old male with sclerosing pnemocytoma with coexistent neuroendocrine hyperplasia and combined carcinoid tumorlets. Taking into account the pluripotentiality of the round cells present in the sclerosing pneumocytoma, with positive staining for stem cells markers, it is possible that the different components of this neoplasia share a common origin, in accordance with previously reported findings.

Pulmonary sclerosing pneumocytoma: clinical features and prognosis.

BACKGROUND: Pulmonary sclerosing pneumocytoma is a kind of rare benign pulmonary tumor with potential malignancy. The clinical features, risk factors for prognosis, and optimal treatment have not been identified yet. This study aimed to investigate the clinical features and prognosis of pulmonary sclerosing pneumocytoma. METHODS: We retrospectively performed a review of pulmonary sclerosing pneumocytoma patients in West China Hospital from 2009 to 2019. The basic characteristics, treatment regimens, operation detail, postoperative variables, and follow-up time were recorded for each case. Differences in features between patients undergoing lobectomy and segmentectomy were compared. We also performed a case review and summarized reported clinical features in former studies. RESULTS: Altogether 61 pulmonary sclerosing pneumocytoma patients were retrospectively reviewed. Fifty-six patients were female and 5 were male. The patients' median age was 51 (23-73). Seven (11.48%) patients had smoking history. Twenty tumors were located in the right lung [upper lobe (n = 7), middle (n = 2), and lower (n = 11)] and 41 in the left [upper (n = 12) and lower (n = 29)]. The median tumor size was 2 (0.9-7) cm. Thirty-six (59.02%) patients underwent sublobectomy (segmentectomy or wedge resection) whereas 25 (40.98%) underwent lobectomy. All patients recovered uneventfully, and no perioperative mortality was identified. Sublobectomy showed a trend towards reduced chest tube duration and shorter postoperative hospital stays compared with lobectomy. CONCLUSIONS: The findings showed good prognosis of pulmonary sclerosing pneumocytoma and proved its benign characteristics. Sublobectomy showed advanced efficacy regarding chest tube duration and postoperative hospital stay compared with lobectomy.

Pulmonary sclerosing pneumocytoma masquerading adenocarcinoma with co-existing BRAF V600E and PTEN mutation.

We report a case of a massive primary sclerosing pneumocytoma (PSP) involving the right lower lobe adhering esophagus with small synchronous PSP on the superior segment of the left lower lobe with concurrent mutation for B-RAF proto-oncogene, serine/threonine kinase (BRAF V600E), and phosphatase and tensin homolog (PTEN) gene in a young female. She underwent right lower lobectomy and mediastinal lymph node dissection under single lung ventilation with tumor-free margins on diagnosis-based findings of preoperative computed tomography-guided biopsy and positron emission tomography. Histopathology was suggestive of PSP-papillary variant with concurrent mutation of BRAF V600E and PTEN genes. Post-operative follow-up at four weeks was uneventful. She has to undergo wedge resection for the contralateral disease after six weeks following recovery from the first surgery.

Unexpected diagnosis of multiple sclerosing pneumocytomas in a patient with chondrosarcoma of the hand.

Sclerosing pneumocytomas are rare, benign pulmonary neoplasms that predominantly affect Asian female patients in the age category of 40-70 years, mostly non-smokers. We report on a 72-year-old Caucasian woman with chondrosarcoma of the hand who developed multiple bilateral progressive lung nodules suspicious of lung metastases. Staged lung resections were performed, and pathological diagnosis was confirmed by immunohistochemical analysis of the resected specimens. Next-generation sequencing (NGS) was used to detect gene mutations. Immunohistochemistry demonstrated sclerosing pneumocytomas, and NGS showed an IDH1 mutation. Eventually, the patient developed lung metastases for which rethoracotomy was performed. The differentiation of sclerosing pneumocytoma from lung cancer is a diagnostic challenge, and sclerosing pneumocytoma should be considered in the differential diagnosis of pulmonary nodules. Gene mutation analysis does not always show classical and common mutations, which should be kept in mind when interpreting its results.

[Analysis of Clinical Characteristics of 35 Cases 
of Pulmonary Sclerosing Pneumocytoma].

BACKGROUND: Pulmonary sclerosing pneumocytoma (PSP) is rare benign lung tumor which usually develops in middle-aged women without typical clinical and imaging findings. PSP consists of two basic cell types (surface cubic epithelial cells and round mesenchymal cells) and four histological types (hemorrhagic, sclerotic, solid and papillary). It grows slowly, but it can metastasize to distant organs. The pathology before surgery is easily misdiagnosed. This study aims to improve clinicians' understanding of PSP by discussing the clinical characteristics of the disease. METHODS: This represents a retrospective study of thirty-five patients diagnosed with pulmonary sclerosing pneumocytoma by pathological examination from January 2011 to December 2019. RESULTS: A total of 35 patients in this study, 12 cases were male and 23 cases were female, the average age is 51 years old. 7 cases were discovered accidentally by physical examination or routine chest computed tomography (CT), and 28 cases were found due to symptoms such as cough, sputum, hemoptysis and chest pain. The imaging changes is mainly featured with isolated or clear circular or round-like single nodule and lump in the lungs. In this group, 12 cases underwent percutaneous lung biopsy, only 7 cases were diagnosed with PSP. A total of 28 patients underwent surgery, 24 cases underwent rapid frozen pathological biopsy, only 5 cases diagnosed with PSP. Postoperative pathological examination results shows that 1 case was diagnosed with keratotic squamous cell carcinoma with partial PSP, and the rest were diagnosed with PSP. The surgical and non-surgical patients were followed up for 1 to 8 years after discharge, and the overall recovery was good. The patients were no recurrence and metastasis on chest CT review. CONCLUSIONS: PSP is a clinically rare benign lung tumor, which is more common in middle-aged women. The clinical manifestations and imaging features are lack of significance. Percutaneous lung puncture pathological examination and intraoperative rapid frozen pathological sections often leads to misdiagnosis. Final diagnosis relies on postoperative pathological work-up for most cases.

[Sclerosing pneumocytoma: A rare and benign tumor]. / Le pneumocytome sclérosant : une tumeur rare et apparemment bénigne.

INTRODUCTION: Sclerosing pneumocytoma is a benign and rare lung tumor affecting epithelial cells. In most cases, patients are asymptomatic and the diagnosis is made on an X ray or a CT scan performed for other enquiry. Sex ratio favors women. Epidemiological studies report that middle-aged Asian women are more frequently affected. Radiological investigations find a solitary nodule or a mass with peripheric localization. When performed, histological analysis shows a tumor composed of at least two of the four following architectures: papillary, sclerosing, hemangiomatous and solid, with two types of cells that can be round or cubic cells. CASES REPORT: We report two cases of multiple sclerosing pneumocytoma in two caucasien men. The first patient was asymptomatic, the second complain from moderate dyspnea. A wedge resection was performed in both, allowing diagnosis. Anatomopathology revealed respectively a predominant sclerosing and solid architecture and a sclerosing and papillary architecture. There was no progression of the other concomitant nodules after three years follow-up. CONCLUSION: Pneumocytoma is a benign, slow-growing tumor with good prognosis.

Clinical and histopathological features of pulmonary sclerosing pneumocytoma with dense spindle stromal cells and lymph node metastasis.

AIMS: To determine the clinicopathological features of pulmonary sclerosing pneumocytoma (PSP) with spindle cells and in cases with positive detection of PSP cells in the lymph nodes. METHODS AND RESULTS: This article report the clinical, histological and immunohistochemical features of PSP with dense spindle stromal cells in five patients (including one case with lymph node metastasis) and PSP accompanied by positive nodes in two patients out of 239 cases diagnosed at our institution between 2007 and 2019. The literature on PSP was also reviewed in detail. Six patients were female, and one (with a positive node) was male; their average age was 53 years. Thoracic imaging revealed solid tumours with clear borders and a uniform texture in six patients, but one patient had a lobulated tumour with uneven densities. All tumours were unifocal, and they had an average size of 31 mm. Tumours from five cases were mainly composed of solid regions of diffuse spindle cells rather than polygonal cells. Immunohistochemical staining demonstrated that thyroid transcription factor-1, vimentin, epithelial membrane antigen (weak) and oestrogen receptor (partial) were expressed in spindle cells. The average follow-up time was 31 months. Two of the 234 PSP cases for which adequate data were available had positive nodes (metastasis rate: 0.8%), and one of the five patients with PSP with spindle cells showed lymph node metastasis (metastasis rate: 20%). In addition, stromal cells were found to be predominant at metastatic sites. CONCLUSIONS: Spindle cells are present among the stromal cells of PSP, and not all of them are round cells. PSP patients with spindle cells or male patients may be more prone to metastasis than others.

Multiple sclerosing pneumocytomas: a review.

Sclerosing pneumocytoma (SP) is a rare benign low-grade tumour of the lung, and typically presents as single discrete coin lesions on imaging. Multiple SP is an exceedingly rare entity and thus reported sparingly. We review the literature on multiple SP, their clinical presentations, histopathology, relevant differential diagnoses and molecular histogenesis of this entity. SP has a predilection for East Asian origin females who have never smoked. Patients are either asymptomatic or have symptoms such as cough, haemoptysis that may be persistent, chest pain if involving the pleura and presents as discrete coin lesion on chest X-ray. Histologically, they are papillary, solid, angiomatoid or sclerotic, or combinations of these four basic patterns. Multiple lesions have the same or slightly different histological patterns. They can be distributed in either lung, in any lobe and can even be bilateral. AKT-1 molecular pathways are pivotal in their molecular pathogenesis. In this review, we further propose a classification based on five types of distribution of multiple SP.

AKT1 internal tandem duplications and point mutations are the genetic hallmarks of sclerosing pneumocytoma.

Sclerosing pneumocytoma is a unique benign neoplasm of the lungs. The molecular alterations in sclerosing pneumocytoma are not well understood. In a previous whole-exome sequencing study, recurrent AKT1 point mutation was observed in about half of the cases of sclerosing pneumocytoma. However, in the remaining half, cancer-related mutations have still not been identified. In this study, we first analyzed the raw sequence data from the previous whole-exome sequencing study (PRJNA297066 cohort). Using Genomon-ITDetector, a special software for detection of internal tandem duplications, we identified recurrent internal tandem duplications in the AKT1 gene in 22 of the 44 tumor samples (50%). All the cases positive for AKT1 internal tandem duplications lacked AKT1 point mutations. Next, we performed targeted next-generation sequencing in an independent cohort of sclerosing pneumocytoma from our hospital (VGH-TPE cohort), and again identified recurrent AKT1 internal tandem duplications in 20 of the 40 (50%) tumor samples analyzed. The internal tandem duplications resulted in duplications of 7 to 16 amino acids in a narrow region of the Pleckstrin homology domain of the AKT1 protein. This region contains the interaction interface between the Pleckstrin homology and kinase domains, which is known to play a critical role in the activation of the AKT1 protein. Moreover, we found that AKT1 internal tandem duplications were mutually exclusive of other forms of AKT1 mutations, including point mutations and short indels. Taking all forms of AKT1 mutations together, we detected AKT1 mutations in almost all the sclerosing pneumocytomas in our study (PRJNA297066 cohort: 41 out of 44 cases, 93%; VGH-TPE cohort: 40 out of 40 cases, 100%). Our results suggest that AKT1 mutation is the genetic hallmark of sclerosing pneumocytoma. These results would help in better understanding of the pathogenesis of sclerosing pneumocytoma.

Concomitance of pulmonary spindle cell carcinoma and sclerosing pneumocytoma in a woman: A case report.

RATIONALE: Pulmonary spindle cell carcinoma (PSCC) is a rare subset of pulmonary sarcomatoid carcinoma. PSCC is aggressive and has a poor prognosis. Pulmonary sclerosing pneumocytoma (PSP) is an asymptomatic slow-growing benign tumor, which usually occurs in middle-aged women. PATIENT CONCERNS: Herein, we report a case of solitary PSCC, occurring concomitantly with PSP in a 74-year-old woman. The patient visited our institution with productive purulent cough, dyspnea after activity, and hemoptysis. Enhanced computed tomography revealed an inhomogeneous enhanced mass with central low-attenuation in the right upper lobe (RUL). The mass located in the right lower lobe (RLL) exhibited homogeneous enhancement. DIAGNOSIS: These lesions were subsequently diagnosed as PSCC in the RUL and PSP in the RLL, following postoperative pathological examination. INTERVENTIONS: We performed lobectomy for the RUL and wedge resection for the RLL in one procedure. OUTCOMES: The patient did not experience complications after surgery. No radiological evidence of recurrence was observed on follow-up computed tomography performed within 7 months after the procedure. LESSONS: This case fully reflects the importance of the differential preoperative diagnosis of benign and malignant solitary pulmonary nodules. However, a rare and aggressive malignant tumor may have imaging features typical of a lung abscess, which should be treated carefully.

Identification of the BRAF V600E mutation in a patient with sclerosing pneumocytoma: A case report.

OBJECTIVES: Sclerosing pneumocytoma (sclerosing hemangioma, SP) is a rare benign tumor of the lung with a low risk of recurrence. The genomic profile of SP is not well-known. Here we report gene mutation findings in a 17-year-old girl with SP. MATERIALS AND METHODS: Immunohistochemistry (IHC), next-generation sequencing (NGS), and sanger sequencing were performed on the tumor tissue of this patient for pathological diagnosis and gene mutation analysis. RESULTS AND CONCLUSION: Two mutations were identified in the tumor tissue by NGS and sanger sequencing: AKT1 E17K and BRAF (B-Raf proto-oncogene, serine/threonine kinase) V600E. This is the first case report of a BRAF V600E mutation in a patient with SP. This discovery extends our understanding of the pathogenesis of SP, and suggests the need for future testing of BRAF V600E in this rare tumor type.

18 F-FDG PET/CT imaging: A supplementary understanding of pulmonary sclerosing pneumocytoma.

BACKGROUND: We sought to investigate the clinical features and 18 F-FDG PET/CT characteristics of pulmonary sclerosing pneumocytoma (PSP). METHODS: We retrospectively reviewed and comparatively analyzed 18 F-FDG PET/CT imaging results of 22 patients with diagnosed PSP in our hospital from November 2009 to September 2015. RESULTS: The SUVmax in tumors was positively correlated with tumor size in typical PSPs (R = 0.806, R2 = 0.650, P = 0.001); however, the SUVmax in tumors had no significant correlation with tumor size of atypical PSPs (R = 0.479, R2 = 0.229, P = 0.162), and the degree of correlation between them attenuated when atypical PSPs were included (R = 0.518, R2 = 0.268, P = 0.011). A majority (90%) of atypical PSPs were found in males. Symptomatic patients showed a higher SUVmax than the asymptomatic group (5.68 ± 3.63 vs. 2.76 ± 1.18, respectively, P = 0.002). CONCLUSION: Tumor size and clinical features may be associated with increased FDG uptake in PSPs. Morphological differences may affect the correlation between tumor size and SUVmax in PSPs. The atypical form of PSP may be more common in men.

Post-tuberculosis Pneumocytoma.

Pneumocytoma is a rare benign tumor of the lung that usually manifests as a solitary pulmonary nodule. A 69-year lady, who had history of tuberculosis treatment 20 years ago, admitted to the hospital. A round mass was seen on chest radiography. Thorax computed tomography was reported as a round lesion in the left lung. Fiberoptic broncoscopy, computed tomography-guided fine-needle aspiration cytology and intraoperative frozen section analyses were undiagnostic. We performed wedge resection with minithoracotomy. Pathologic examination was reported as pneumocytoma. The patient did not receive any chemotherapy or radiotherapy after the operation. After 41 months' follow-up, no recurrent lesion was seen.

Symptomatic pulmonary sclerosing hemangioma: a rare case of a solitary pulmonary nodule in a woman of advanced age.

BACKGROUND: Pulmonary sclerosing hemangioma (PSH) is a rare tumor that usually develops in middle-aged Asian women. PSH has four histological types (hemorrhagic, sclerotic, solid, and papillary) and often grows slowly in a lower lobe of the lung. Preoperative misdiagnosis frequently occurs because of the absence of specific clinical manifestations and imaging findings. Few reports have described PSH in women of advanced age. Case presentation: A 75-year-old woman presented to our hospital in China with a 5-day history of productive cough and intermittent hemoptysis. Computed tomography indicated bronchiectasis and a large mass in the left inferior lobe of the lung. Treatment of the bronchiectasis provided no symptom relief. The hemoptysis resolved following left lower pulmonary lobectomy, and PSH was pathologically diagnosed following surgery. At the time of this writing (after 6 months of follow-up), the tumor had not recurred, no metastases had been detected, and close follow-up was ongoing. CONCLUSIONS: Both bronchiectasis and PSH can cause hemoptysis. This case demonstrates that PSH should be included as a differential diagnosis of hemoptysis in women of advanced age. For patients with chronic hemoptysis, the diagnosis of PSH should be considered if the therapeutic effect of bronchiectasis is poor.

Sclerosing pneumocytoma: Case report of a rare endobronchial presentation.

RATIONALE: Sclerosing pneumocytoma is a rare benign lung neoplasm seen in middle aged adults with a female predominance. Originally thought to be vascular in origin, this rare entity is now understood to be epithelial in nature. On imaging, sclerosing pneumocytoma manifests as a well circumscribed nodule or mass, often juxtapleural in location. On histopathology, sclerosing pneumocytoma is composed of cuboidal "surface cells" and round "stromal cells," both of which show nuclear staining for thyroid transcription factor-1 (TTF-1). Here we review the existing literature on sclerosing pneumocytoma and present a case of sclerosing pneumocytoma in a highly unusual endobronchial location. PATIENT CONCERNS: This case is a 43 year old woman who presented with chronic cough. DIAGNOSIS: Imaging revealed a right upper lobe nodule with an endobronchial component. INTERVENTIONS AND OUTCOMES: Endoscopic biopsy was performed, and pathologic diagnosis was confirmed. LESSONS: Although extremely rare, endobronchial presentation of sclerosing pneumocytoma is possible, and should remain on the differential for patients with endobronchial pulmonary lesions. Pathologic tissue analysis is necessary to confirm this uncommon diagnosis.