Formation Of Large Cysts Research Articles

THU551 Glycoprotein-NMB (GPNMB) Is A Potential Lymphangioleiomyomatosis (LAM) Therapeutic Target And Biomarker

Abstract Disclosure: E. Gibbons: None. S.R. Hammes: None. Lymphangioleiomyomatosis (LAM) is a rare, progressive, destructive cystic lung disease affecting almost exclusively female-sexed individuals. Mutations in the tuberous sclerosis (TSC1 or TSC2) genes constitutively activate the mTORC1 pathway, promoting hyperproliferation of smooth muscle cells, creating small tumors throughout the lungs. These tumors, through largely unknown mechanisms, result in the formation of large cysts that replace normal alveolar space. Inhibition of mTORC1 with Sirolimus slows but does not stop LAM progression; therefore, there is a need for new LAM treatment options and biomarkers. Due to LAM’s estrogen sensitivity, female specificity, and metastatic nature, we previously proposed LAM cells originate from the uterine myometrium. We therefore designed a uterine-specific TSC2-null mouse model where all the mice generate uterine tumors characteristic of LAM and half develop lung metastases, suggesting that indeed LAM tumors may be derived from the uterus. Using bulk RNASeq analysis of uterine tissue from our mouse model, when focusing on genes regulated by estrogen and TSC2, we discovered increased expression of melanocytic markers, including Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB), a known oncogenic protein in other cancers. GPNMB was not only highly expressed in our mouse model; it was also expressed intracellularly and on the cell surface of TSC2-null cell lines and in LAM tumor cells from patient lungs and uteri. Notably, the extracellular domain of GPNMB was released from the surface of TSC2-null cell lines, suggesting that the ectodomain may also be released from TSC2-null cells in LAM patients. Here we show that, GPNMB protein and mRNA expression increased when the cells were serum starved, mimicking conditions of a tumor microenvironment. This increase was dependent on mTORC1 signaling and mRNA transcription. Knocking down GPNMB expression by siRNA had minimal effects on TSC2-null cells pro-tumorigenic functions in vitro aside from decreasing invasion. However, knocking out GPNMB in TSC2-null cells using CRISPR/Cas9 significantly decreased mouse xenograft tumor growth. Additionally, treating mice with a GPNMB antibody drug conjugate abrogated xenograft growth, highlighting GPNMB’s potential as a therapeutic target. Also, GPNMB’s ectodomain was released from the cell surface of TSC2-null cells by the proteases Adam10 and 17. Of note, the ectodomain is implicated in mediating GPNMB’s effects on tumor growth, suggesting that Adam10/17 inhibition may mitigate TSC2-null tumor growth. Importantly, the GPNMB ectodomain is a potential serum biomarker of LAM, as there was a significant increase in GPNMB ectodomain levels in patient serum as compared with healthy controls. Furthermore, serum GPNMB levels decreased in most patients after Sirolimus treatment, implicating GPNMB as a potential marker for responsiveness to treatment. Presentation: Thursday, June 15, 2023

Poster 303: Radiographs Demonstrate Poor Interrater Reliability and Accuracy for Evaluation of Postoperative Healing for Osteochondral Allograft Transplants of the Knee

Objectives: To evaluate the reliability of radiographs to evaluate healing of osteochondral allografts in the knee compared to CT scans as gold standard imaging. Methods: A retrospective review of prospectively enrolled patients who underwent osteochondral allograft transplantation for focal chondral defects of the knee was performed. At 6 months, all patients prospectively underwent CT scan of the knee. A retrospective review was performed to assess knee radiographs obtained in clinic at 3 and 6 months postoperatively. Three board-eligible orthopaedic sports fellows independently graded available radiographs while remaining blinded to the CT scan results. Separately, two board-eligible orthopaedic sports fellows graded CT scans utilizing the ACTOCA system, and their consensus measurements served as the gold standard for this study. Intraclass correlation (ICC) with a two-way random effects model and kappa coefficients were calculated for grades between the three raters. Results: Among the 44 grafts prospectively imaged, 13 (29.5%) grafts had radiographs at 3 months and 28 (63.6%) grafts had radiographs available for evaluation at 6 months. Among three graders, assessment of integration demonstrated low to moderate reliability (ICC: 0.25-0.41). Contrary to this, assessment of qualities such as graft sclerosis and cyst formation on radiographs demonstrated poor interrater reliability with inability to reject the null hypothesis that all grades were assigned randomly (p>0.05) (Table 1). At 6 months, in patients with large cysts (> 3 mm) on CT, only 2/18 (11%) were accurately detected on radiographs and 5/18 (27.8%) were underestimated as small cysts. In patients with small cysts (< 3 mm) on CT, only 4/42 grafts (9.5%) were accurately graded, and 3/42 (7.1%) evaluated grafts were overestimated to have large cysts (Figure 1). Among patients who had small or large cysts at 6 months, only 1/21 (4.8%) and 1/3 (33.3%) radiographic assessments detected this cystic change at 3 months, respectively. Patients with crossing trabeculae on CT were associated with a mean radiographic integration score of 81.0 ± 15.7, which was significantly greater than those with a discernible cleft < 3 mm (mean 68.7 ± 19.3, p=0.01). However, these groups were not significantly different than radiographic scores for grafts that had discernible clefts > 3 mm (80.0 ± 19.7, p>0.05). Among the 23 patients with a 6-month radiograph available, 4 required subsequent surgery for symptomatic failure. Three (75%) of these patients demonstrated large cyst formation on CT scan at 6 months. Conclusions: Evaluation of osteochondral allograft healing by radiographs alone may be inaccurate and associated with missed abnormalities such as cyst formation. [Table: see text]

RF19 | PSUN351 Glycoprotein-NMB (GPNMB) is Pro-Tumorigenic in Lymphangioleiomyomatosis (LAM)

Abstract Lymphangioleiomyomatosis (LAM) is an estrogen-sensitive lung disease found almost exclusively in women. LAM is characterized by the hyperproliferation of smooth muscle cells creating small tumors throughout the lungs, resulting in the formation of large cysts that replace normal alveolar space. Growth of these tumors and progression of cyst development leads to loss of pulmonary function, and sometimes subsequent lung transplantation. LAM tumor cells contain mutations in one of the tuberous sclerosis genes (TSC1 or TSC2), leading to constitutive activation of the mTORC1 pathway. In fact, mTOR inhibitors are commonly used to treat LAM; however, these drugs are not always effective and have significant side effects, suggesting the need for new therapeutic targets. Additionally, tumors recur even after lung transplantation and LAM cells are found in circulating body fluids, suggesting a metastatic nature of LAM, and a question of the origin of the LAM cell. Due to LAM's estrogen sensitivity, female specificity, and metastatic nature, we previously proposed that LAM cells originate from the uterine myometrium. We therefore designed a uterine-specific TSC2-null mouse model where all of the mice generate uterine tumors characteristic of LAM and half develop lung metastases, suggesting that indeed LAM tumors may be derived from the uterus. Notably, our collaborators recently utilized single cell RNA sequencing with human LAM lung lesions, and found that TSC2-null cells have a strong uterine profile. Using bulk RNASeq analysis of uterine tissue from our mouse model, when focusing on genes regulated by estrogen and TSC2, we discovered increased expression of melanocytic markers, including Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB). GPNMB is known to be oncogenic in other cancers and has been shown to be expressed intracellularly in benign cells, but both intracellularly and on the cell surface of tumor cells making GPNMB a good cell surface drug target. This melanocytic marker was not only highly expressed in our mouse model, it was also expressed in TSC2-null cell lines, as well as in human LAM patient lung and uteri samples. Knocking down GPNMB expression by siRNA directed against GPNMB mRNA decreased proliferation, migration, and invasion in TSC2-null cells. We also found that GPNMB's large ectodomain is released from the cell surface of TSC2-null cells and potentially mediated by the protease, Adam10. The ectodomain specifically is implicated in mediating GPNMB's effects on tumor growth. Finally, knocking out GPNMB in TSC2-null cells using CRISPR/Cas9 decreased xenograft tumor growth in mice. Overall, our data thus far demonstrate that GPNMB promotes TSC2-null tumor growth and metastasis. Importantly, the GPNMB ectodomain is a potential biomarker of human LAM, as we detect a significant difference in GPNMB ectodomain levels in patient blood as compared with healthy controls. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m.

Glycoprotein-NMB (GPNMB) is Pro-Tumorigenic in Lymphangioleiomyomatosis (LAM)

Abstract Lymphangioleiomyomatosis (LAM) is an estrogen-sensitive lung disease found almost exclusively in women. LAM is characterized by the hyperproliferation of smooth muscle cells creating small tumors throughout the lungs, resulting in the formation of large cysts that replace normal alveolar space. Growth of these tumors and progression of the cyst development leads to pulmonary function loss, and sometimes subsequent lung transplantation. However, LAM recurs after transplantation and LAM cells can be found circulating in body fluids suggesting a metastatic nature of the disease. Due to LAM’s estrogen sensitivity, female specificity, and metastatic nature, we previously proposed that LAM cells originate from the uterine myometrium. We therefore designed a uterine-specific TSC2-null mouse model where all of the mice generate uterine tumors characteristic of LAM and half develop lung metastases. Using RNASeq analysis of uterine tissue from this mouse model, when focusing on genes regulated by estrogen and TSC2, we discovered increased expression of melanocytic markers, including Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB), which is known to be oncogenic in other cancers. GPNMB was not only highly expressed in our mouse model, it was also expressed in TSC2-null cell lines, and LAM patient lungs and uteri. Interestingly, serum GPNMB is a potential biomarker, as LAM patients have higher serum GPNMB levels compared to healthy controls. Knocking down GPNMB expression by siRNA decreased proliferation, migration, and invasion in TSC2-null cells. Further, knocking out GPNMB in TSC2-null cells using CRISPR/Cas9 decreased xenograft tumor growth in mice and GPNMB is a potential therapeutic target for LAM. Supported by grants from NIH (R01 CA193583, T32HL066988), the LAM Foundation, and DOD

Результаты применения противоспаечного геля после моделирования контузионного повреждения спинного мозга у крыс

Objective was to investigate an effect of anti-adhesion hyaluronic-containing resorbable gel on the course of traumatic spinal cord disease caused by a simulated contusion spinal cord injury (SCI) in rats. Material and methods A moderate spinal cord injury was simulated at the Th9 level of 40 female Wistar rats that were randomly divided into 2 groups. Group I received hyaluronic-containing absorbable antiadhesion gel Antiadgezin® that was intraoperatively applied to the dura mater of experimental rats; Group II of control rats received no gel. The BBB locomotor rating scale was used to evaluate the extent of recovered pelvic limb function. The animals were sacrificed on days 5, 15, 30, 60 and 90. Paraffin and epoxy semi-thin 1 μm sections were used for morphological examination of the spinal cord using light microscopy. Results The gel used for contusion SCI in rats caused neither significant changes during postoperative period nor local infectious and inflammatory complications, and showed no negative impact on functional results. Morphological examination revealed pathomorphological changes that were identical for both groups and characteristic of contusion SCI showing softening, necrosis of the nervous tissue, tissue and cell detritus of gray and white matter, small cysts in the early stages of the experiment; progression of syringomyelia and formation of large cysts primarily seen in the gray matter and the onset of regenerative processes in the white matter at 60 and 90 days of the experiment. Conclusion The absence of a negative effect of the anti-adhesion hyaluronic-containing resorbable gel on the functional results, and morphological characteristics of the spinal cord offer the opportunity of the further experimental use as a carrier of substance composition initiating beneficial metabolic and neuroprotective action for transdural delivery in simulated SCI.

Pro-Tumorigenic Role of Neutrophil Elastase in Lymphangioleiomyomatosis (LAM)

Abstract Lymphangioleiomyomatosis (LAM) is an estrogen-sensitive lung disease found almost exclusively in women. LAM is characterized by the hyperproliferation of smooth muscle cells creating small tumors throughout the lungs, resulting in the formation of large cysts that replace normal alveolar space. Growth of these tumors and progression of the cyst development leads to loss of pulmonary function, and sometimes subsequent lung transplantation. LAM tumor cells contain mutations in one of the tuberous sclerosis genes (TSC1 or TSC2), leading to activation of the mTORC1 pathway. In fact, mTOR inhibitors are commonly used to treat LAM; however, these drugs are not always effective and have significant side effects, suggesting the need for new therapeutic targets. Additionally, tumors recur even after lung transplantation and LAM cells are found in circulating body fluids, suggesting a metastatic nature of LAM, and a question of the origin of the LAM cell. Due to LAM’s estrogen sensitivity, female specificity, and metastatic nature, we previously proposed that LAM cells originate from the uterine myometrium. We therefore designed a uterine-specific TSC2-null mouse model where all the mice generate uterine tumors characteristic of LAM and half develop lung metastases. Using RNASeq analysis of uterine tissue from this mouse model, when focusing on genes regulated by estrogen and TSC2, we discovered significant upregulation of inflammatory proteases such as Neutrophil Elastase (NE). NE is secreted by myeloid cells such as polymorphonuclear cells (PMNs) and has been reported to promote invasion, migration, and proliferation in various cancers. We found this to be true in LAM as well, as depleting myeloid cells with an antibody directed against PMNs, or inhibiting NE with the NE inhibitor, sivelestat, markedly decreased TSC2-null uterine tumor growth. NE is released when PMNs undergo Neutrophil Extracellular Trap release, or NETosis. NETosis has been shown to have a pro-tumorigenic role in various cancers and we are investigating the effects of NETosis in LAM. We have also generated a novel uterine-specific TSC2-null mouse in the background of no NE to determine whether uterine tumor burden and lung metastases are reduced in NE-null mice and if these mice have PMNs capable of undergoing NETosis in the absence of NE. Overall, our results suggest that NE release from PMNs is critical for LAM tumor development and may be a novel target for its treatment.

Prevalence, Structure, and Distribution of Novel Parasite Cysts Containing Dracunculus Species in River Otters ( Lontra canadensis) from Arkansas.

Adult female guinea worms ( Dracunculus spp.) usually are reported to occur singly in the extremities of their hosts, from which they deliver their larvae into the water through fistulae in the host's skin. We visually examined for the presence of worms in the fascia of the limbs of skinned carcasses of 184 river otters ( Lontra canadensis) harvested in Arkansas and report observations of cysts on wrists and ankles found on 12 otters. Cysts averaged 15.6 × 24.6 mm in diameter, were round to oval, and contained masses of up to 19 adult female Dracunculus sp. (mean 6.7). We speculate that high levels of infection in consumed paratenic hosts might have caused high infection rates, leading to large cyst formation in otters, as larvigerous Dracunculus sp. females accumulated in extremities. No males were discovered during the study, so identification of a sample of worms was based on molecular techniques.

Use of human induced pluripotent stem cell-derived neurons as a model for Cerebral Toxoplasmosis

Toxoplasma gondii is a ubiquitous protozoan parasite with approximately one-third of the worlds' population chronically infected. In chronically infected individuals, the parasite resides primarily in cysts within neurons in the central nervous system. The chronic infection in immunocompetent individuals has been considered to be asymptomatic but increasing evidence indicates the chronic infection can lead to neuropsychiatric disorders such as Schizophrenia, prenatal depression and suicidal thoughts. A better understanding of the mechanism(s) by which the parasite exerts effects on human behavior is limited due to lack of suitable human neuronal models. In this paper, we report the use of human neurons derived from normal cord blood CD34+ cells generated via genetic reprogramming, as an in vitro model for the study T. gondii in neurons. This culture method resulted in a relatively pure monolayer of induced human neuronal-like cells that stained positive for neuronal markers, MAP2, NFL, NFH and NeuN. These induced human neuronal-like cells (iHNs) were efficiently infected by the Prugniad strain of the parasite and supported replication of the tachyzoite stage and development of the cyst stage. Infected iHNs could be maintained through 5 days of infection, allowing for formation of large cysts. This induced human neuronal model represents a novel culture method to study both tachyzoite and bradyzoite stages of T. gondii in human neurons.

A Patient With Intrahepatic Cholangiocarcinoma With Large Cyst Formation Presenting With Right Flank Pain

We report a patient with intrahepatic cholangiocarcinoma with large cyst formation. A 60-yearold female presented with a one-day history of right flank pain. Abdominal ultrasonography and enhanced computed tomography (CT) revealed an approximately 10cm cystic mass accompanying a solid lesion. On physical examination, there was pain on percussion and slight tenderness in the right flank. Laboratory data showed slightly elevated LDH and an elevated CA19-9. Neither communication between the cystic lesion and the bile duct nor intrahepatic bile duct dilatation were observed on magnetic resonance cholangiopancreatography (MRCP). A right hepatic lobectomy was performed with a preoperative diagnosis of cystadenocarcinoma adjacent to the right hepatic vein. A 10cm cystic mass with a relatively thick wall protruding laterally and dorsally was found intraoperatively. The resected specimen contained brown turbid fluid and a 5.5x4cm solid lesion inside the cyst, and 1.8x1.5cm solid lesion in the adjacent liver. Histopathological examination showed papillary adenocarcinoma with proliferation of degenerated bile ductules contiguous with the cyst wall. This lesion was diagnosed as an intrahepatic cholangiocarcinoma with cyst formation. We must consider intrahepatic cholangiocarcinoma with cyst formation in the differential diagnosis when investigating and treating a cystic liver tumor.Figure 1Figure 2Figure 3

588 Perinatal Factors Associated with Multiple Large Cysts on Chest Computed Tomography in Extremely Premature Infants with Chronic Lung Disease

ObjectiveTo identify perinatal factors associated with multiple large cysts on chest computed tomography (CT) in extremely premature infants with chronic lung disease (CLD).MethodsA case-control study of 87 infants with CLD...

Grainyhead-like 2 regulates epithelial morphogenesis by establishing functional tight junctions through the organization of a molecular network among claudin3, claudin4, and Rab25

During development, epithelial progenitors establish intercellular junctions, including tight junctions (TJs), and form three-dimensional (3D) tissue structures, which are often associated with luminal structures. Here we identify grainyhead-like 2 (Grhl2) as a transcription factor that regulates the size of luminal space surrounded by polarized epithelial cells. We show that HPPL, a liver progenitor cell line, transfected with Grhl2 cDNA forms remarkably larger cysts than the control cells in 3D cultures. We find that Grhl2 up-regulates claudin (Cldn) 3 and Cldn4, and their functions are necessary for the formation of large cysts. Overexpression of Cldn3 alone induces the cyst expansion. In contrast, expression of Cldn4 alone does not induce expansion, as it is not localized at TJs. Of interest, Rab25, another Grhl2 target, not only increases the Cldn4 protein, but also enhances its localization at TJs. Taken together, the results indicate that Grhl2 regulates epithelial morphogenesis through transcriptional up-regulation of Cldn3 and Cldn4, as well as of Rab25, which increases the Cldn4 protein and its localization at TJs. The results reveal a molecular network regulating epithelial lumen formation organized by Grhl2.

Lung adenocarcinoma with giant cyst formation showing a variety of histologic patterns: a case report

IntroductionLung cancer with large cyst formation is relatively rare. This is a case report of a patient with lung cystic adenocarcinoma with multiple histologic patterns. This type of lung adenocarcinoma is believed to be the first reported case in English language medical literature.Case presentationA 60-year-old Japanese woman was admitted to hospital complaining of dyspnea and died of respiratory failure. She had been suffering from lung cancer with pleural effusion for five years. Autopsy analysis revealed lung adenocarcinoma with large cyst formation showing a variety of histologic patterns.ConclusionsAutopsy analysis of this atypical case of lung cancer may provide insight and lead to a better understanding of the heterogeneity and clonal expansion of lung adenocarcinoma.

Membrane-type-1 matrix metalloproteinase confers tumorigenicity on nonmalignant epithelial cells

Overexpression of membrane-type-1 matrix metalloproteinase (MT1-MMP) in tumor cells has previously been shown to enhance tumor growth and metastasis. To establish if MT1-MMP is also able to confer tumorigenicity on nonmalignant epithelial cells, we transfected human MT1-MMP cDNA into Madin-Darby canine kidney (MDCK) cells expressing a tetracycline-repressible transactivator. Induction of MT1-MMP in the absence of doxycycline (Dox) was associated with activation of exogenous MMP-2 as well as with formation of large cysts and increased invasiveness in collagen matrices. Transfected cells were inoculated subcutaneously into two groups of nude mice, one of which received Dox to inhibit expression of MT1-MMP. Formation of tumor xenografts was observed in 11 of 17 mice maintained without Dox, but only in two of nine mice that received Dox (P<0.05). The xenografts were composed of tubular structures interspersed within a highly cellular stroma. The epithelial cells delimiting the lumen were polarized, as indicated by the basolateral distribution of Na,K-ATPase. Despite their differentiated appearance, the tumors lacked a well-defined boundary, and epithelial tubules invaded adjacent muscular layers. These results demonstrate that conditional expression of MT1-MMP in nonmalignant MDCK epithelial cells is by itself sufficient to drive formation of invasive tumors.

Brain stem glioblastoma with multiple large cyst formation and leptomeningeal dissemination in a 4-year-old girl

The authors report a 4-year-old girl who developed brain stem glioblastoma. Meningeal irritation was present at onset. Magnetic resonance imaging revealed intracranial and intraspinal leptomeningeal dissemination, which progressed faster than the original tumor. Multiple large cysts developed at the interhemispheric and prepontine cisterns, resulting in progressive obstructive hydrocephalus. The patient survived only 5 months after presentation. Histology was verified by autopsy.

Progressive segregation of unmyelinated axons in peripheral nerves, myelin alterations in the CNS, and cyst formation in the kidneys of myelin and lymphocyte protein-overexpressing mice.

Myelin and lymphocyte protein (MAL) is a putative tetraspan proteolipid that is highly expressed by Schwann cells and oligodendrocytes as a component of compact myelin. Outside of the nervous system, MAL is found in apical membranes of epithelial cells, mainly in the kidney and stomach. Because MAL is associated with glycosphingolipids, it is thought to be involved in the organization, transport, and maintenance of glycosphingolipid-enriched membrane microdomains. In this report, we describe the generation and analysis of transgenic mice with increased MAL gene dosage. Immunohistochemical analysis revealed that the localization of MAL overexpression in the transgenic animals corresponded closely to the MAL expression pattern observed in wildtype animals, indicating correct spatial regulation of the transgene. Phenotypically, MAL overexpression led to progressive dissociation of unmyelinated axons from bundles in the PNS, a tendency to hypomyelination and aberrant myelin formation in the CNS, and the formation of large cysts in the tubular region of the kidney. Thus, increased expression of MAL appears to be deleterious to membranous structures in the affected tissues, indicating a requirement for tight control of endogenous MAL expression in Schwann cells, oligodendrocytes, and kidney epithelial cells.

Brain Cavernoma: A Dynamic Lesion

Background Although the prevalence of brain cavernomas is high (0.50%), for unknown reasons, only a few of them display aggressive clinical behavior. Methods From a personal series of 65 operated and histopathologically verified cavernomas, we have conducted a long-term study, both retrospectively and prospectively, of the main features that cause some cavernomas to be dynamic lesions. Results Hemorrhage is the most common phenomenon. Extralesional bleeding due to the rupture of peripheral caverns is most often observed. These are never as immediately devastating as hemorrhages originating from a high-flow, high-pressure AVM. Extralesional hemorrhages tend toward spontaneous resorption, but the risk of recurrence exists and may lead to permanent disability or death (especially when the lesion is located in the brain stem). Intralesional bleeding caused by rupture of contiguous caverns is less frequently observed. This may lead to the formation of large cysts. Calcifications are mostly observed in patients presenting with chronic epilepsy. The bleeding risk of calcified cavernomas is low, but it can exist and should be taken into account in the surgical decision making. The growth of the cavernomatous matrix was obvious in three large cavernomas (two with calcification). No bleeding was found inside the lesions, suggesting a pure “intrinsic” growth. The role of pathologic angiogenic factors is highly probable in these cases. “De novo” appearing lesions were observed in five cases (four belonging to familial forms) on the magnetic resonance imaging survey of operated patients. Perilesional atrophy was observed in three cases (two operated) in patients with a long-lasting evolution. It suggests that the brain metabolism can be disturbed by slow, chronic effusion of blood around the cavernoma. Conclusions The dynamism of cavernomas is determined by extrinsic factors, mainly hemorrhage (with its own consequences); and by intrinsic factors: the pseudotumoral growth of the cavernous matrix. Therefore, when they are symptomatic, cavernomas should be totally removed.

Salivary gland anlage tumor. A case with widespread necrosis and large cyst formation

We describe a case of the salivary gland anlage tumor (congenital pleomorphic adenoma). The tumor arose in the nasopharynx as a pedunculated mass. Microscopically most of the tumor contained large necrotic areas which revealed squamous cell metaplasia resulting in the formation of large cysts. This feature has never been described previously in this tumor and might lead to an erroneous diagnosis.

Serial changes of cystic air spaces in fibrosing alveolitis: A CT-pathological study

In patients with cryptogenic fibrosing alveolitis (CFA), subpleural large cysts are sometimes seen within honeycombing on computed tomography (CT). These cysts may be interpreted as bullae and the coexistence of emphysema with CFA might be assumed. We evaluated whether cystic spaces in honeycombing become larger in patients with CFA on serial CT scans. CT scans were obtained in 16 patients with CFA, who had undergone two CT examinations (6 to 43 months, mean 25.1 months apart), were reviewed focusing on the changes in size of the cystic spaces in honeycombing. The mechanism of enlargement of cystic spaces was investigated using microscopic serial sections of autopsied specimens. In 15 of 16 patients, the cystic spaces in honeycombing were larger on the second examination. Histologically, stenosis of bronchioles and slit-like structures between cysts and bronchioles were detected in addition to alveolar septal dissolution and bronchiolectasis. Both the bronchiolar stenosis and the slit-like gaps have the potential to work as check-valves and increase the volume of cystic spaces. Therefore, in the evaluation of CFA, large cysts should be interpreted with caution to avoid misinterpretation of the cysts as bullae associated with emphysema. From the results of this correlative study, we suggest that a check-valve effect is an important mechanism in the formation of large cysts in honeycomb lung.

耳下腺に生じた大きな嚢胞形成を伴う多形性腺腫の１症例

多形性腺腫は唾液腺で最も多くみられる腫瘍であり, その多彩な病理組織学的所見が大きな特徴の一つである。本腫瘍において, 病理組織学的にしばしば小さな嚢胞がみられるが, 肉眼的にみられるような大きな嚢胞を形成することはまれである。今回, 28歳男性の左側耳下腺にみられた, 大きな嚢胞を伴う多形性腺腫の1例を経験したので報告した。各種検査を行ったが, 今回は, 造影CTによる所見が診断に最も有効であった。腫瘍は外科的に摘出し, 病理組織学的に多形性腺腫の診断を得た。術後5年を経過するが再発の傾向なく, 経過良好である。

Pedunculated pulmonary leiomyoma with large cyst formation

A case of single pulmonary leiomyoma with giant cyst formation is presented. Metastasizing uterine fibroleiomyoma and fibroleiomyomatous hamartoma both give rise to multiple pulmonary nodules on chest films. Leiomyoma of the lung presenting as a single pedunculated lesion with cyst formation is exceptional. This report documents the existence of other rate cystic lesions that may mimic the more common cystic air space and bullous disease.