Pulmonary lymphangioleiomyomatosis followed by a localized retroperitoneal lymphangioleiomyoma

Lymphangioleiomyomatosis is a rare disease that affects females of reproductive age. Microscopically, it is characterized by abnormal proliferation of immature smooth muscle-like cells that grow diffusely in the lung. Extrapulmonary manifestations in the mediastinum, peritoneum and pelvic lymph nodes are uncommon. We here describe a patient who initially presented with pulmonary lymphangioleiomyomatosis and subsequently developed a localized retroperitoneal mass. Pathologic examination showed that the mass was a lymphangioleiomyoma. The result of the immunohistochemical study was the same as that for the pulmonary lesion. It is therefore suggested that metastatic lymphangioleiomyoma should be included in the differential diagnosis in the patient with pulmonary lymphangioleiomyomatosis presenting with an extrapulmonary lesion.     

Florid cystic endosalpingiosis of the spleen

A case of endosalpingiosis appearing as a huge multilocular cyst in the spleen of a 31-year-old woman is reported. The cystic lumens were smooth, and lined by fallopian tubal epithelium containing ciliated and secretory cells. The epithelial lining showed neither atypia nor foci of papillary proliferation, with only 3-5% MIB-1 labeling index. The epithelial lining was histochemically negative for mucin, but positive for MUC1 and progesterone receptor. Despite the appearance of a tumor-like mass, it was diagnosed as florid cystic endosalpingiosis as there was a normal tube-like epithelium. Regarding etiology, it was considered to derive from the secondary müllerian system of the splenic capsule.     

Uterine angiosarcoma associated with lymphangioleiomyomatosis in a patient with tuberous sclerosis complex: an autopsy case report with immunohistochemical and genetic analysis

A 41-year-old woman carrying a germline tuberous sclerosis complex 2 (TSC2) mutation, whose regular medical follow-up for tuberous sclerosis complex and tuberous sclerosis complex-associated lymphangioleiomyomatosis had continued for 2 years, had uterine angiosarcoma concomitant with uterine lymphangioleiomyomatosis. Immunohistochemically, the uterine angiosarcoma cells showed an extremely skewed lymphatic differentiation; they were diffusely immunopositive for CD31 but negative for other vascular endothelial markers including factor VIII and CD34 yet strongly immunopositive for lymphatic endothelial markers including D2-40 and Prox-1. Loss of heterozygosity analysis demonstrated that not only lymphangioleiomyomatosis and renal angiomyolipoma but also the uterine angiosarcoma had loss of heterozygosity on TSC2. Furthermore, direct sequencing revealed a TP53 mutation in the uterine angiosarcoma. Collectively, the findings suggest that combined dysfunction of the p53 and TSC2 tumor suppressor proteins may contribute to the development of uterine angiosarcoma in this rare clinical setting.     

Retroperitoneal lipomatous angiomyolipoma associated with amyloid deposition masquerading as well-differentiated liposarcoma

Reported herein is a case of retroperitoneal angiomyolipoma associated with amyloid deposition, masquerading as well-differentiated liposarcoma. A 16 x 13 cm lipomatous tumor was resected from the perirenal retroperitoneum of a 71-year-old woman. Microscopically, the tumor was exclusively composed of mature adipose tissue and abnormal thick blood vessels, but bundles of smooth muscle were lacking. In addition, amyloid was deposited between fat cells. Initially, well-differentiated liposarcoma was highly suspected. However, there were a few epithelioid cells with clear vacuolated cytoplasm within the vessel walls, which were immunoreactive for smooth muscle markers and HMB-45. Real-time polymerase chain reaction failed to demonstrate the amplification of the murine double-minute type 2 gene and cyclin-dependent kinase 4 gene in this tumor. Therefore, the tumor was diagnosed as lipomatous angiomyolipoma. After the diagnosis, it was found that the patient had multiple myeloma and cardiac amyloidosis, suggesting that the amyloid deposition within the tumor was a complication of the myeloma. Lipomatous angiomyolipoma may be a diagnostic pitfall of retroperitoneal lipomatous tumors.     

Oncogenic BRAF and KRAS mutations in endosalpingiosis

Endosalpingiosis, a microscopic lesion composed of ectopic Fallopian tube epithelium, frequently involves the peritoneum and lymph nodes in patients with ovarian serous borderline tumour or low-grade serous carcinoma, but its pathogenic significance remains unclear. Using laser-capture microdissection and droplet digital PCR, we investigated whether endosalpingiosis harbours the driver mutations in BRAF and KRAS that characterise ovarian low-grade serous neoplasms. Somatic mutations were detected in 14 (33%) of 43 endosalpingiotic lesions analysed. Of 21 women with endosalpingiosis associated with a synchronous or metachronous ovarian low-grade serous tumour, mutations were identified in endosalpingiotic lesions from 11 (52%) women, with most cases (10/11, 91%) demonstrating identical mutations in both tumour and endosalpingiosis. In contrast, of 13 cases of endosalpingiosis not associated with an ovarian tumour, only one harboured a KRAS mutation. The proliferative activity as assessed by Ki-67 immunohistochemistry was lower in endosalpingiosis than in low-grade serous tumours, and endosalpingiosis with either a BRAF or KRAS mutation had a significantly lower Ki-67 index than those without. Ectopic expression of KRAS^G12V in Fallopian tube epithelial cells led to ERK phosphorylation, p21 induction, growth arrest and cellular senescence. In conclusion, we demonstrate that endosalpingiosis represents an interesting example of cancer driver mutations in deceptively normal-appearing cells, which may be prone to neoplastic transformation upon bypass of endogenous oncosuppressive mechanisms. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Cytologic diagnosis of endosalpingiosis with pregnant women presenting in peritoneal fluid: a case report

The cytologic appearance of endosalpingiosis in peritoneal fluid cytology smears has not been extensively described. We report a case of endosalpingiosis in a 29-year-old pregnant female who presented with peritoneal fluid. Dense papillary epithelial clusters with indistinct ciliated cells were found in the Papanicolaou-stained smears. However, long and delicate cilia were obvious in papillary cluster with scanning electron microscopy. Cell nuclei were oval, with finely dispersed chromatin and uniform nuclear membrane. Peritoneal fluid cytology with these findings may be helpful to suggest the probable preoperative diagnosis of endosalpingiosis or benign glandular inclusions involving the pelvic peritoneum.     

Retroperitoneal dedifferentiated liposarcoma with osteosarcomatous components: a case report

We report a rare case of recurrent retroperitoneal dedifferentiated liposarcoma with osteosarcomatous components. An 82-year-old male diagnosed with recurrent retroperitoneal liposarcoma underwent a tumor resection. Histologically, osseous matrix with osteoid and mature hyaline cartilaginous tissues with high cellularity were observed in a fibrous background through most of the tumor, and scattered MDM2- and CDK4-positive atypical hyperchromatic stromal cells were detected surrounding the dedifferentiated areas. Dedifferentiation occurs in up to 10% of well-differentiated liposarcomas, frequently resembling a malignant fibrous histiocytoma-like pleomorphic sarcoma. In contrast, divergent differentiation with osteosarcomatous components is considered to be extremely rare.     

Retroperitoneal leiomyosarcoma of a male centenarian

An autopsy case of retroperitoneal leiomyosarcoma of a centenarial male is described. He complained of abdominal pain In his left side 1 month before his death. Ultrasonog-raphy and computed tomography revealed a large mass in the left abdominal cavity. At autopsy, a circumscribed mass, 15 cm in diameter, was found in the left-upper abdominal cavity, and seemed to be derived from the retroperitoneum in an exophytic manner. Histologically, spindle cells with slight eosinophillc cytoplasm and blunt-ended nuclei showed interwoven fascicular growth, and mitotic figures were easlly encountered. Immunohlstochemically, the tumor cells were labeled by α-smooth muscle actln and vimentln. To our knowledge, this case of leiomyosarcoma has presented in the oldest patient ever reported. The rarity of soft tissue sarcomas in the extremely elderly is also discussed.     

Lineage tracing suggests that ovarian endosalpingiosis does not result from escape of oviductal epithelium

Most high-grade serous carcinomas are thought to arise from Fallopian tube epithelium (FTE), but some likely arise outside of the tube, perhaps from ectopic tubal-type epithelium known as endosalpingiosis. Importantly, the origin of endosalpingiosis is poorly understood. The proximity of the tubal fimbriae to the ovaries has led to the proposal that disruptions in the ovarian surface that occur during ovulation may allow detached FTE to implant in the ovary and form tubal-type glands and cysts. An alternative model suggests that cells present in ectopic locations outside the Müllerian tract retain the capacity for multi-lineage differentiation and can form glands with tubal-type epithelium. We used double transgenic Ovgp1-iCreER^T2;R26R^LSL-eYFP mice, which express an eYFP reporter protein in OVGP1-positive tissues following transient tamoxifen (TAM) treatment, to track the fate of oviductal epithelial cells. Cohorts of adult mice were given TAM to activate eYFP expression in oviductal epithelium, and ovaries were examined at time points ranging from 2 days to 12 months post-TAM. To test whether superovulation might increase acquisition of endosalpingiosis, additional cohorts of TAM-treated mice underwent up to five cycles of superovulation and ovaries were examined at 1, 6, and 12 months post-TAM. Ovaries were sectioned in their entirety to identify endosalpingiosis. Immunohistochemical staining for PAX8, tubulin, OVGP1, and eYFP was employed to study endosalpingiosis lesions. Ovarian endosalpingiosis was identified in 14.2% of TAM-treated adult mice. The endosalpingiotic inclusion glands and cysts were lined by secretory and ciliated cells and expressed PAX8, tubulin, OVGP1, and eYFP. Neither age nor superovulation was associated with a significant increase in endosalpingiosis. Endosalpingiosis was also occasionally present in the ovaries of pre-pubertal mice. The findings imply that ovarian endosalpingiosis in the mouse does not likely arise as a consequence of detachment and implantation of tubal epithelium and other mechanisms may be relevant. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Retroperitoneal kaposiform hemangioendothelioma with tufted angioma-like features in an infant with Kasabach-Merritt syndrome

Kasabach-Merritt syndrome denotes profound thrombocytopenia and coagulopathy in an infant with a vascular tumor. A retroperitoneal vascular tumor with an unusual combination of histopathological features is reported, and compared with vascular lesions described in the reported cases of Kasabach-Merritt syndrome in the literature. A large retroperitoneal tumor that had expanded through the sigmoid mesocolon into the sigmoid colon wall was resected from an 8-month-old infant with fully developed Kasabach-Merritt syndrome. Histological examination revealed a combination of venous (cavernous) malformation, kaposiform hemangioendothelioma and tufted angioma-like areas. Cellular tumor components (especially tufted angioma-like parts) infiltrated the wall of the sigmoid colon to the submucosal level. Immunohistochemical staining with antibodies to the Ki-67 antigen and proliferating cell nuclear antigen showed a low proliferative activity, whereas the antiapoptotic bcl-2 protein was expressed diffusely in tumor cells. This is the first reported case of a vascular tumor with tufted angioma-like elements found in the retroperitoneum, and the first reported in combination with kaposiform hemangioendothelioma and venous malformation in the same lesion. Considering the immunohistochemical results and overlapping histological features, it may be considered that tufted angioma and kaposiform hemangioendothelioma represent different growth patterns or stages in the development of a single type of hemangioma.     

Retroperitoneal epithelioid angiomyolipoma leading to fatal outcome

Epithelioid angiomyolipoma (AML) is a newly established variant of AML, characterized by monomorphous epithelioid cells that show HMB-45 immunopositivity, and it often displays aggressive behavior. To date, they have mostly appeared in the kidneys; however, the present autopsy case of a 43-year-old female without the stigmata of tuberous sclerosis complex had a huge retroperitoneal mass, accompanied by involvement of the regional lymph nodes. Histopathologically, the tumor was composed of round, polygonal or short spindle-shaped monomorphous cells with abundant eosinophilic cytoplasm and large nuclei with frequent multinucleation. Mitotic figures were scattered. Mature fat cells and thick-walled abnormal blood vessels were totally absent. Immunohistochemically, the tumor cells were reactive with HMB-45 and alpha-smooth muscle actin antibodies. In spite of curative surgery and repeated radio- and chemotherapy, the tumor continued to grow and brought about the patient's death 4 years after the initial symptoms. At autopsy, the peritoneal cavity was filled with the tumor mass exceeding 5.5 kg. Histopathological features were essentially the same as those of biopsy samples, but the cellular pleomorphism and emperipolesis were more easily identified. This report calls attention to this unusual manifestation of AML in the retroperitoneum and the importance of distinguishing it from sarcomas and/or paragangliomas.     

Association of lymphangioleiomyomatosis (LAM) with endosalpingiosis in the retroperitoneal lymph nodes: report of two cases

We report 2 patients in whom pulmonary lymphangioleiomyomatosis (LAM) affected the retroperitoneal lymph nodes and was associated with endosalpingiosis. These lesions were large, encapsulated masses with multiple cysts containing chylous fluid. Both were characterized by proliferating LAM cells that formed fascicles separated by slit-like channels. Some cysts were lined by ciliated epithelium resembling that of Fallopian tubes. Other cysts were lined either by flattened endothelial cells or by a mixture of these cells and epithelial cells. Many LAM cells gave a positive reaction with HMB-45 antibody. Most LAM cells in fascicles were reactive for alpha-smooth muscle actin and desmin. In 1 patient, many of the epithelial cells and some of the subjacent LAM cells were positive for estrogen and progesterone receptors. In conclusion, immunostaining with HMB-45 antibody and markers for smooth muscle cells can be helpful in the evaluation of problems in the differential diagnosis of lesions of extrapulmonary LAM, particularly those involving the genital system.     

Peritoneal epithelial lesions associated with proliferative serous tumours of ovary

The peritoneal epithelial lesions in 40 cases of proliferating ovarian serous tumour are described. The lesions were varied and of both neoplastic and non-neoplastic form. The most common was serous tumour similar to that in the associated ovarian neoplasm. Tumour of this type was present in some or all of the peritoneal lesions in 77.5% of cases. In nearly two-thirds, the tumour was superficial; in the rest it invaded omentum. Occasionally, the infiltrating tumour was poorly differentiated. Benign tubular lesions resembling endosalpingiosis occurred in 16 (40%) of the 40 cases, but in seven it was associated with serous tumour. Psammoma bodies frequently accompanied serous tumour and endosalpingiosis and in occasional cases the majority of lesions consisted of psammomatous foci. The duration of follow up is too short to adequately assess the biological significance of these findings but it is clear that the peritoneal tumour occasionally may kill the patient within a few years. 'Serous tumour of low malignant potential' is the most appropriate term to describe the general group of ovarian serous tumours of so-called 'borderline malignant' type.     

Retroperitoneal bronchogenic cyst: Report of a case and literature review

A large cystic mass was found in the subdiaphragmatic region of a 46-year-old woman who had complained of continuous pain in the left flank . The cyst was located in the retroperitoneum just below the diaphragm and was adhered to the diaphragmatic skeletal muscle and abdominal aorta, but was separate from the spleen, pancreas, left adrenal gland and left kidney. The surgically resected cyst measured 8 x 8 x 7 cm and was filled with protein-rich fluid, which contained amylase and embryonal proteins such as carcinoembryonic antigen, CA125 and CA19-9. Histologically, the cyst wall was composed of a fibrovascular connective tissue containing thin smooth muscle layers and mucus-secreting glands and was lined by a ciliated pseudostratified or tall columnar epithelium without dysplastic changes. Thus, a diagnosis of bronchogenic cyst, which is usually discovered in the posterior part of the mediastinum, was made. A rare case of bronchogenic cyst and a literature review is presented.     

Retroperitoneal mucinous cystadenoma: report of two cases and review of the literature

Primary retroperitoneal cystic tumor is extremely rare, and its histogenesis and biological behavior remain speculative. Two surgical cases of retroperitoneal mucinous cystadenoma (Case 1, an 18-year-old woman; and Case 2, an 85-year-old woman) are reported. The cystadenomas in these cases were mainly lined by a monolayer of columnar or thin flat cells. Case 1 was positive for mucin and epithelial membrane antigen, whereas Case 2 was positive for a mesothelial marker (calretinin). Ciliated epithelium was also interspersed in Case 2. Some parts showed papillary projections, resembling well-differentiated papillary mesothelioma. Within the cyst walls of both cases, ovarian-like stroma that was positive for both estrogen and progesterone receptors was found. Interestingly, focal nodular hyperplasia of the liver was also detected in Case 1. We believe the retroperitoneal mucinous cystadenoma might have arisen from the peritoneum via mucinous epithelial metaplasia with a phenotype of extragenital Mullerian system.     

Multifocal alveolar hyperplasia associated with lymphangioleiomyomatosis in tuberous sclerosis

Multifocal alveolar hyperplasia associated with pulmonary lymphangioleiomyomatosis is reported in a 21-year-old woman with tuberous sclerosis. Beside the cystic lesions of lymphangioleiomyomatosis, the tomography showed nodules up to 8 mm in both upper lobes. A proliferation of type II pneumonocytes and Clara cells lining the alveolar walls in an adenoma-like pattern was observed. Nuclear atypia, mitoses and necrosis were not observed, providing evidence against multicentric bronchioloalveolar carcinoma or micronodular atypical alveolar adenomatous hyperplasia. Whereas the lymphangioleiomyomatosis lesions showed strong positivity for HMB45 and expressed oestrogen and progesterone receptors, the alveolar hyperplasia was negative for these markers as it was for carcinoembryonic antigen, p53 and MIB1 antibodies. Multifocal alveolar hyperplasia in tuberous sclerosis is probably a benign hamartomatous lesion in our case without progression on a 2-year follow-up. Its histogenesis is unknown, but is possibly related to chromosome instability.     

Multifocal alveolar hyperplasia associated with lymphangioleiomyomatosis in tuberous sclerosis

Multifocal alveolar hyperplasia associated with pulmonary lymphangioleiomyomatosis is reported in a 21-year-old woman with tuberous sclerosis. Beside the cystic lesions of lymphangioleiomyomatosis, the tomography showed nodules up to 8 mm in both upper lobes. A proliferation of type II pneumonocytes and Clara cells lining the alveolar walls in an adenoma-like pattern was observed. Nuclear atypia, mitoses and necrosis were not observed, providing evidence against multicentric bronchioloalveolar carcinoma or micronodular atypical alveolar adenomatous hyperplasia. Whereas the lymphangioleiomyomatosis lesions showed strong positivity for HMB45 and expressed oestrogen and progesterone receptors, the alveolar hyperplasia was negative for these markers as it was for carcinoembryonic antigen, p53 and MIB1 antibodies. Multifocal alveolar hyperplasia in tuberous sclerosis is probably a benign hamartomatous lesion in our case without progression on a 2-year follow-up. Its histogenesis is unknown, but is possibly related to chromosome instability.     

Retroperitoneal ganglioneuroma: A report of diagnosis by fine-needle aspiration cytology

Ganglioneuroma is a rare benign tumor composed of nerve fibers and mature ganglion cells. Because it shares morphologic features with other neural tumors, both benign and malignant, accurate preoperative diagnosis is often difficult, but nonetheless, critical for proper management. The use of fine-needle aspiration (FNA) cytology in the diagnosis of ganglioneuroma has been rarely documented. In this report, a 25-yr-old man presented with a large retroperitoneal ganglioneuroma that was initially diagnosed by FNA cytology. This case illustrates the utility of FNA cytology in the diagnosis of ganglioneuroma and supports the routine incorporation of FNA cytology in the evaluation of retroperitoneal masses. Diagn. Cytopathol. 1998;19:385–387. © 1998 Wiley-Liss, Inc.