Benign metastasizing leiomyoma of the uterus: histologic and immunohistochemical characterization of primary and metastatic lesions.

Benign uterine leiomyoma metastasizing to the lung is a recognized entity that has been reported infrequently in the medical literature. There is persisting controversy regarding the pathogenesis and biology of these lesions. We report a well-studied and well-characterized case of benign leiomyoma metastasizing to the lung. The patient was a 72-year-old woman with an enlarged uterus that contained several leiomyomas with usual histology. Areas of fibrosis, hyalinization, edema, and focal infarction together with small foci with mildly increased cellularity and minimal nuclear pleomorphism were seen. Careful and repeated mitotic counts ranged from 0 to 2 mitoses per 10 high-power fields. In summary, based on histopathologic criteria, the neoplasm was determined to be a focally cellular benign leiomyoma. Four years later, the patient underwent surgical resection of a single nodule in the lung, which had been detected on routine radiographs. Histopathologic evaluation showed a low-grade leiomyosarcoma with moderate nuclear pleomorphism, necrosis, and brisk mitotic activity. Immunohistochemical studies performed on both neoplasms showed them to be of mesenchymal derivation with smooth muscle differentiation. Both neoplasms expressed estrogen receptors with moderate to strong intensity. The patient received no further treatment and, to date, shows no evidence of recurrent disease. The diagnosis of benign metastasizing leiomyoma can only be made with certainty after careful and extensive sampling of the primary tumor to exclude small foci of sarcoma and of the pulmonary tumor to rule out a primary neoplasm. Although it is biologically peculiar, benign metastasizing leiomyoma should continue to be recognized as a distinct entity because current morphologic criteria do not allow primary myometrial tumors to be reclassified as leiomyomas of uncertain malignant potential even if they have metastasized to the lung.     

Malignant rhabdoid tumour of the uterus: an immunohistochemical and ultrastructural study

Summary Malignant rhabdoid tumours (MRTs) are highly aggressive neoplasms which most frequently occur in the kidney of young children. Several cases of primary MRT occurring in extra-renal sites have been reported, particularly in the soft tissues. We report a case of primary MRT of the uterus, a very rare site for this neoplasm, with morphological, immunohistochemical and ultrastructural features corresponding to restrictive morphological criteria for MRT. The possible differential diagnoses were considered.     

Epithelioid trophoblastic tumor of the uterus: cytological and immunohistochemical observation of a case

Epithelioid trophoblastic tumor (ETT) is a new entity of trophoblastic tumor and 14 such cases were reported by Shih and Kurman in 1998. However, only three subsequent cases supporting ETT have been reported. Recently, we experienced a case of ETT in a 37-year-old woman whose preoperative endometrial brushings showed atypical mononucleate giant cells and who underwent hysterectomy with the diagnosis of a uterine fibroid. The specimens revealed a 2.5 x 3.0 cm yellow-tan intramural nodule located in the lower uterine segment, which was composed of a neoplastic proliferation of intermediate trophoblasts in epithelioid arrangements. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin and inhibin-alpha, and focally positive for human chorionic gonadotropin and human placental lactogen. She presented an uneventful clinical course as of September 2001.     

Perivascular epithelioid cell tumor of the uterus: immunohistochemical, ultrastructural and molecular study

A case of perivascular epithelioid cell tumor of the uterus is reported, occurring in a 32-year-old woman. The tumor (8.0 cm in dimension) showed exophytic growth from the outer half of the myometrium. Histopathologically, the tumor was composed of thick blood vessels and perivascular epithelioid cells. The neoplastic cells were strongly immunoreactive for HMB45 antigen, CD117 (c-kit), vimentin and the progesterone receptor, but completely negative for S-100 protein, smooth muscle actin, desmin, CD34, the estrogen receptor and p16. The Ki-67 labeling index was low (1.25%). Ultrastructurally, the neoplastic cells had numerous premelanosomes with some glycogen deposits. Single-stranded DNA conformational polymorphism of p53 and methylation-specific polymerase chain reaction of p16 revealed negative results. Definite melanosomes on electron microscopic analysis and coexpression of HMB45 antigen and stem cell factor receptor (CD117) may provide the clue to understanding perivascular epithelioid cell tumor because angiomyolipoma also coexpresses HMB45 antigen and CD117.     

Histological and immunohistochemical observations of dedifferentiated leiomyosarcoma of the uterus.

A case of dedifferentiated leiomyosarcoma of the uterus was examined using immunohistochemistry. The tumor arose in the myometrium, and was a whitish large nodule with hemorrhage and necrosis. Histologically it was a well differentiated leiomyosarcoma with foci showing epithelioid pattern, and in part resembling malignant fibrous histiocytoma (MFH) and giant cell tumor (GCT). Additionally, small round neoplastic cells arranged in an alveolar manner, simulating alveolar rhabdomyosarcoma, were seen in some areas. Neoplastic cells in well differentiated areas expressed desmin, muscle-specific actin and LeuM1, whereas those in epithelioid and poorly differentiated areas lacked these antigens. Instead, tumor cells in epithelioid and small round cell areas were positive for keratin. Interestingly, most tumor cells in well differentiated, epithelioid and small round cell areas were also positive for MB1. However, tumor cells in GCT- and MFH-like areas reacted with none of the antibodies used. Ultrastructurally, some tumor cells possessed various amounts of microfilaments with or without dense patches, whereas others lacked them. These findings suggest that the divergent antigen expression was attributable to different levels of differentiation, and that poorly differentiated components had lost their native features.     

Atypical polypoid adenomyoma of the uterus: A reappraisal of the clinicopathological and immunohistochemical features

Atypical polypoid adenomyoma (APAM) is an uncommon uterine mixed epithelial and mesenchymal tumor. The discrimination from endometrial carcinoma remains to be clarified. In this study, we compared the clinicopathological and immunohistochemical features between 36 APAMs and 48 endometrial carcinomas. APAM with a highly complex structure (n?=?13) coexisted with atypical hyperplasia (n?=?5) and endometrial carcinoma (n?=?1). Two patients had endometrial carcinomas at 1 and 102 months. Four patients recurred at 1–57 months but none died of disease. The fibromuscular stroma demonstrated 3 uncharacterized features: a broad bundle (10/36), a lobular structure separated by the stromal branches (26/36), and the extension of fibromuscular stroma underneath the surface epithelium (31/36). However, these features were not seen in endometrial carcinomas except the vaguely lobular pattern. Both APAM and endometrial carcinoma showed a similar immunostaining pattern except high Ki67 index in endometrial carcinomas (p?<?0.05). Our study suggests that the distinct features of the fibromuscular stroma can aid in the differential diagnosis between APAM and endometrial carcinoma.     

Atypical polypoid adenomyoma of the uterus: an immunohistochemical study on 5 cases

Immunohistochemical studies of atypical polypoid adenomyoma (APA) of the uterus are very rare. Five cases of APA were retrieved from the surgical cases of our laboratory. The ages were 38, 41, 54, 65, and 77 years (mean ± SD, 55 ± 14.6 years). The diameters of APA were 1.2, 1.9, 2.3, 3.2, and 7.0 cm (mean ± SD, 3.12 ± 2.00 cm). Histologically, APA consisted of complex glandular element and mesenchymal fibromuscular element. No endometrial stroma was present. Mucins were found in the glands but not in the mesenchyma. The glands were consistently positive for pancytokeratin (AE1/3, CAM5.2), cytokeratin (CK) 7, CK8, CK18, CK19, vimentin, CA125, estrogen receptor, progesterone receptor, MUC1, and MUC6. The glands were consistently negative for CK14, CK20, CEA, epithelial membrane antigen, S100 protein, p53, CD10, MUC2, and MUC5AC. Some cases were positive for CK34βE12 (4/5), CK5/6 (4/5), and CA19-9 (4/5). The Ki-67 labeling ranged from 3% to 10%. The mesenchymal element was consistently positive for vimentin, α-smooth muscle actin, estrogen receptor, progesterone receptor, and CD10, while consistently negative for pancytokeratin (AE1/3, CAM5.2), CK34βE12, CK5/6, CK7, CK8, CK14, CK18, CK19, CK20, CEA, epithelial membrane antigen, S100 protein, CA125, CA19-9, p53, MUC1, MUC2, MUC5AC, and MUC6. Some cases were positive for desmin (2/5). Ki-67 labeling ranged from 1% to 8%. In conclusion, the immunoprofile of APA was reported. The findings provide basic knowledge of APA of the uterus.     

Primary osteosarcoma of the uterus: report of a case with immunohistochemical study.

A 63-yr-old female presented with uncontrollable uterine bleeding. Pathological evaluation revealed a uterine mesenchymal neoplasm which histologically represented a primary osteosarcoma. Immunohistochemistry was utilized to help support the diagnosis. The English literature regarding this rare uterine neoplasm is briefly reviewed.     

Pregranulomatous phase of sarcoidosis: immunohistochemical diagnosis

Histopathological confirmation of clinical suspicion of sarcoidosis is based on the finding of non-caseating granulomas in biopsy material, usually in prescalene lymph nodes or in transbronchial lung biopsies. Lymph node reactive sinus histiocytosis (RSH) seen in relation to various inflammatory and non-inflammatory diseases can mimic the pregranulomatous phase of sarcoidosis (PSH). Differentiation of sinus histiocytosis based on histopathological features alone is limited. The purpose of this study is immunohistochemical determination of lymph node cellular response in granulomatous sarcoidosis, the PSH and RSH using a immunohistochemistry employing a panel of antibodies. Patient groups under study each contained 25 patients and included: those with clinical picture of sarcoidosis and non-caseating granulomatous lymphadenitis; those with confirmed sarcoidosis and with sinus histiocytosis without granuloma formation in lymph nodes; and finally, those without sarcoidosis and with “reactive” sinus histiocytois in lymph nodes. Lymph node biopsy tissue was fixed in buffered formaldehyde, routinely processed to paraffin wax blocks, cut into 4-μm-thick sections, stained with hematoxylin and eosin and immunohistochemically labelled using a triple-layer APAAP protocol with purified polyclonal antibodies directed against SP 70 and SP90 from Mycobacterium tuberculosis and monoclonal antibodies against CD22, CD4, CD8, CD56, and CD68. Intensity of immunolabelling was assessed semiquantitatively by two independent observers.

An increased CD4:CD8 ratio, moderate increase of immunolabelling for CD68 and slight decrease in immunolabelling for CD20, CD56, and SP90 was indicative of PSH when compared with RSH. The most notable difference between the studied groups was a difference in imunoreactivity to SP70 and CD4 antibodies. Lymph nodes with pregranulomatous sinus histiocytosis labelled with both antibodies. This profile of immunolabelling can be used in the differentiation of this condition from reactive sinusoidal lesions.     

Phenotypic and immunohistochemical characterization of sarcoglycanopathies

INTRODUCTION:

Limb-girdle muscular dystrophy presents with heterogeneous clinical and molecular features. The primary characteristic of this disorder is proximal muscular weakness with variable age of onset, speed of progression, and intensity of symptoms. Sarcoglycanopathies, which are a subgroup of the limb-girdle muscular dystrophies, are caused by mutations in sarcoglycan genes. Mutations in these genes cause secondary deficiencies in other proteins, due to the instability of the dystrophin-glycoprotein complex. Therefore, determining the etiology of a given sarcoglycanopathy requires costly and occasionally inaccessible molecular methods.

OBJECTIVE:

The aim of this study was to identify phenotypic differences among limb-girdle muscular dystrophy patients who were grouped according to the immunohistochemical phenotypes for the four sarcoglycans.

METHODS:

To identify phenotypic differences among patients with different types of sarcoglycanopathies, a questionnaire was used and the muscle strength and range of motion of nine joints in 45 patients recruited from the Department of Neurology – HC-FMUSP (Clinics Hospital of the Faculty of Medicine of the University of São Paulo) were evaluated. The findings obtained from these analyses were compared with the results of the immunohistochemical findings.

RESULTS:

The patients were divided into the following groups based on the immunohistochemical findings: α-sarcoglycanopathies (16 patients), β-sarcoglycanopathies (1 patient), γ-sarcoglycanopathies (5 patients), and non-sarcoglycanopathies (23 patients). The muscle strength analysis revealed significant differences for both upper and lower limb muscles, particularly the shoulder and hip muscles, as expected. No pattern of joint contractures was found among the four groups analyzed, even within the same family. However, a high frequency of tiptoe gait was observed in patients with α-sarcoglycanopathies, while calf pseudo-hypertrophy was most common in patients with non-sarcoglycanopathies. The α-sarcoglycanopathy patients presented with more severe muscle weakness than did γ-sarcoglycanopathy patients.

CONCLUSION:

The clinical differences observed in this study, which were associated with the immunohistochemical findings, may help to prioritize the mutational investigation of sarcoglycan genes.     

Adenomatoid tumor of the uterus. Ultrastructural, histochemical, and immunohistochemical analysis

A uterine tumor from a 34-year-old woman was investigated morphologically and immunohistochemically. The tumor tissue was composed of multiple cystic spaces of various sizes. The cyst wall was covered by a single layer or occasionally multiple layers of flattened cells. Electron micrographs of the tumor tissue revealed that the cells were delimited with conspicuous basal lamina from the stroma, possessed numerous microvilli at the apical surface, and connected with desmosomes. Furthermore, immunohistochemical staining with antikeratin antibody disclosed the strong positivity of the tumor cells, whereas anti-UEA-I antibody could not stain the tumor cells. The results did not favor the theory of endothelial origin of the tumor and confirmed the mesothelial origin, namely, adenomatoid tumor of the uterus.     

Serous adenocarcinoma of the uterus: criteria of morphological diagnosis and immunohistochemistry

The analysis of the histopathologic features in 138 patients with uterine serous adenocarcinoma in comparison with 146 patients with uterine endometrioid papillary adenocarcinoma revealed morphological specificities of these carcinomas. Immunohistochemical study found that 66.7% uterine serous adenocarcinomas were negative both to estrogen and progesterone receptors and 86.7% uterine serous adenocarcinomas showed p53 oncoprotein overexpression. The data support the hypothesis that uterine serous adenocarcinoma is a hormone-negative tumor and that mutation of p53 tumor suppressor gene may play a leading role in its carcinogenesis.     

Blue rubber bleb nevus syndrome: novel lymphangiomatosis-like growth pattern within the uterus and immunohistochemical analysis

Blue Rubber Bleb Nevus Syndrome is a rare, primarily sporadic condition characterized by vascular lesions principally involving the skin and gastrointestinal tract. Although considered a venous malformation, telangiectatic capillaries, arteriovenous malformations, and lymphangiomas have been reported, but a lymphangiomatosis-like growth pattern has not been described. This case of Blue Rubber Bleb Nevus Syndrome demonstrated a labyrinth of variably sized vascular spaces lined by an attenuated layer of bland endothelial cells, dissecting uterine tissues and sequestering remaining myometrium. Immunohistochemical profile of lesional endothelial cells from the myometrium included strong, diffuse CD31; variable CD34; strong, patchy D2-40; weak, patchy factor VIII-related antigen; focal linear subendothelial collagen type IV; Ki-67 in 1% of cells; and no GLUT-1 or WT1 expression. This report expands the morphological spectrum of vascular lesions in Blue Rubber Bleb Nevus Syndrome to include a lymphangiomatosis-like growth pattern and the immunohistochemistry suggests dual vascular and lymphatic differentiation, supporting the current belief that these lesions are malformations.     

Primary signet-ring cell carcinoma of the lung: histochemical and immunohistochemical characterization

To establish criteria for differential diagnosis and to clarify the histogenesis of primary signet-ring cell carcinoma (SRCC) of the lung, five cases were studied by mucin-histochemical and immunohistochemical analyses and compared with SRCC of the gastrointestinal tract and mucus-producing adenocarcinoma of the lung. The proportion of signet-ring cell component varied from 10% to 90% in four cases, and the remaining tumor was a pure SRCC. Mucin-histochemistry showed a close similarity between lung SRCC and goblet cell-type or bronchial gland cell-type adenocarcinoma of the lung. Eighty percent of SRCCs showed positive immunoreactions for lactoferrin, a marker of bronchial gland cell differentiation, the results being consistent with the conclusions in previous studies that lung SRCC is closely related to bronchial gland cell-type adenocarcinoma. The incidence of K-ras mutation detected by the restriction fragment length polymorphism method was relatively high in lung SRCC (three of five) and goblet cell-type adenocarcinoma of the lung (four of four). Mucin-histochemistry indicated that lung SRCC has mucin production similar to that of the colon and colorectal-type SRCCs of the stomach but not to that of gastroduodenal-type SRCC of the stomach. Immunohistochemical staining for MUC-1 and MUC-2 glycoproteins showed a distinct difference; lung SRCC was positive for MUC-1 but negative for MUC-2, whereas colon SRCC and colorectal-type gastric SRCC were negative for MUC-1 but positive for MUC-2.Thus, by a combination of mucin-histochemistry and MUC-1 and MUC-2 immunohistochemistry, primary lung SRCC can be distinguished from metastatic lung SRCC originating in the gastrointestinal tract.     

Pheochromocytomas and ganglioneuromas in the aging rats: morphological and immunohistochemical characterization

We investigated, morphologically and immunohistochemically, 74 medullary adrenal tumors, including 64 pheochromocytomas (14 malignant and 50 benign), 9 ganglioneuromas, and 1 malignant schwannoma. The tumors were detected in 2-year-old Wistar and Sprague-Dawley rats from carcinogenicity studies. Morphologically, benign pheochromocytomas were characterized by monomorphic, small, basophilic cells with almost absence of mitoses. Malignant pheochromocytomas presented a low grade of pleomorphism, higher rate of mitoses, necrosis, infiltrative growth and in 1 case metastases in the lung. Ganglioneuromas were characterized by ganglion and neuron-like cells embedded in an eosinophilic matrix containing neurites, Schwann cells, and scant fibrovascular elements. All pheochromocytomas were strongly immunoreactive for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Subpopulations of chromaffin cells expressed chromogranin A (CGA) positivity. Matrix and Schwann cells were positive for S-100 and for glial fibrillary acidic protein (GFAP). In focal areas of the tumors, ganglion cells and axons were positive for neurofilament proteins (NFP) and synaptophysin. Ganglion cells exhibited peripherin and beta-tubulin. Proliferative activity of the tumors was assessed by immunostaining the endogenous cell proliferation associated-antigen Ki-67 and the proliferating cell nuclear antigen (PCNA). As expected, cell proliferation indices were much higher in malignant pheochromocytomas than in benign, yet ganglioneuromas remained immunonegative. Considering that Ki-67 antigen is more specific for cell proliferation, it should be regarded as marker of choice for supporting the differential diagnosis between benign and malignant pheochromocytomas.     

Benign metastasizing leiomyoma of the uterus: documentation of clinical, immunohistochemical and lectin-histochemical data of ten cases

The clinical histories of 10 women suffering from benign metastasizing leiomyoma (BML) after hysterectomy and information on lung lesions detected in these women are presented, together with corresponding data for 2 women with metastasizing leiomyosarcoma of the uterus for comparison: gross appearance, survival, and light microscopical, immunohistochemical and lectin-histochemical findings are reported. All patients with BML had undergone hysterectomy for uterus leiomyomatosus without any detection of sarcomatous lesions in the uterus wall. After a median period of 14.9 years intrapulmonary masses were detected by imaging techniques. On average, six nodules with a mean diameter of 1.8 cm were seen. Resection of the lesions was performed in all cases. The immunohistochemical and lectin-histochemical examination of the tumors included analysis of the proliferation-associated protein Ki-67, the p53 protein, estrogen and progesterone receptor, sarcolectin as an indicator of the presence of lymphokine macrophage migration inhibitory factor, antibodies and the labeled protein to assess galectin (galactoside-binding animal lectin)-dependent parameters, analysis of tumor vascularization (CD-34), and expression of bcl-2, vimentin, smooth muscle actin, desmin, and keratin. The lesions were characterized by low proliferation activity of 2.9% (measured with Ki-67), frequent hormone receptor expression (8 of the 10 cases presented hormone-specific receptors), low to moderate vascularization compared with metastases from the two uterine sarcomas, remarkable p53 overexpression and frequent expression of the lymphokine, the galectins and accessible binding sites. The median survival of the BML patients was 94 months after excision of the intrapulmonary lesions, and the maximum survival of the two sarcoma patients was 22 months. The results recorded in this patient sample with the methodology applied suggest that benign metastasizing leiomyomas are a slow-growing variant of leiomyosarcoma of the uterus, which becomes clinically apparent at a young age and progresses with low velocity. Received: 27 December 1999 / Accepted: 11 February 2000     

子宫腺肉瘤的临床病理特点及鉴别诊断

目的：分析子宫Ｍｕｅｌｌｅｒｉａｎ腺肉瘤的临床病理特点及其鉴别诊断。方法：观察１３例子宫腺肉瘤临床病理特点，并进行组织化学和免疫组化染色分析。结果：病人年龄２６￣６７岁，主要表现为阴道不规则流血和子宫增大。肿瘤位于宫体内膜、宫颈内膜和子宫肌壁。镜下腺上皮呈Ｍｕｅｌｌｅｒｉａｎ上皮系列。间质细胞异型分级为Ⅰ￣Ⅱ级，核分型４￣３２个／１０ＨＰＥ，具有腺周套袖和息肉样突入腺腔的结构。４例伴肉瘤过度生长。     

Cytomorphological diagnosis of nonepithelial tumors of the uterus

Retrospective histocytological correlations are performed of the material from 38 patients with non-epithelial uterine tumours. Cytomorphological features of highly, moderately and poorly differentiated leiomyosarcoma, leiomyoblastoma, endometrial stromal sarcoma, mixed mesodermal tumours and botryoid sarcoma are established.     

Sarcomas of the Female Genitalia: Therapy and Prognosis

216 sarcomas of the female genitalia were treated at the University hospitals for women of Freiburg and Tübingen between the years 1957 to 1977. 76% originated from the uterine corpus; 28% (46/164) of the sarcomas of the corpus uteri were detected as incidental findings. The 5 year survival rate is 54% in stage I, 25% in stage II, and 40% in all stages (52/131). Postoperative irradiation of stage I cases of sarcomas of the corpus uteri diminished local recurrence but not metastases. Extirpation of the ovaries has no influence on local recurrence.Sarcomas of the vulva and cervix have a comparatively good prognosis, whereas the prognosis of the sarcoma of the ovary is very bad.The bad prognosis of sarcomas of the female genitalia points out the necessity of developing cooperative clinical trials on the effectiveness of adjuvant chemotherapy.