Clear CelI HepatocelIular Caxinoma with Abundant Myxoid Stroma

A case of the clear cell variant of hepatocellular carcinoma with an abundant myxoid stroma is presented. The tumor occurred in a 55 year old Japanese man, and swelling of the scrotum was the initial symptom. The patient underwent high-level orchiectomy, and the pathologic diagnosis was a metastatic tumor on the surface of the processus vaginalis and intact testis. Extensive examination failed to show a primary site. Subsequent autopsy revealed a large hepatic tumor and metastatic nodules with a prominent myxoid appearance in multiple organs. Histological-ly, each tumor consisted of uniform small tumor cells with clear cytoplasm attributed to abundant accumulation of glycogen particles, and an abundant myxoid stroma was also present. The tumor cells were positive for keratin, α1– antitrypsin, α1-antichymotrypsin, liver ferritin, prealbumin, and fibrinogen, but lacked α fetoprotein. These findings indicated that this case was hepatocellular carcinoma of the clear cell type with a prominent myxoid stroma. Acta Pathol Jpn 42: 897–903, 1992.     

Synchronous renal cell carcinoma and clear cell hepatocellular carcinoma mimicking metastatic disease

Double carcinomas of hepatocellular and renal cell carcinoma (RCC) are extremely rare, and among the reported cases, none of the hepatocellular carcinomas show clear cell change. We report a case of synchronous double primary clear cell tumor in the liver and the kidney of a 70-year-old male. The renal mass was a renal cell carcinoma of mixed clear and granular cell types, and the hepatic mass was a hepatocellular carcinoma with extensive clear cell change that mimicked a metastatic renal cell carcinoma. A simple battery of immunohistochemical stains composed of hepatocyte antigen, and CD10 was performed to make a definite diagnosis.     

Klarzelltumor der Lunge

Clear cell tumors of the lung are rare tumors composed of epithelioid HMB45 positive tumor cells. It has been proposed that clear cell tumors generate from perivascular epithelioid cells which are also found in renal angiomyolipoma. Due to its morphologic epithelioid features with clear cytoplasm the distinction from either primary or metastatic clear cell carcinoma is difficult. Usually clinical investigations do not lead to the final diagnosis so that only subsequent histological examination and immunophenotyping can establish the correct tumor classification. We describe the case of a 52 year old woman who underwent exploratory thoracotomy because of a lung mass in the right lower lobe. In frozen sections a solid trabecular tumor was diagnosed, paraffin histology and immunohistochemistry revealed a clear cell tumor of the lung. The difficulty of the correct diagnosis of the clear cell tumor of the lung in frozen sections is discussed as well as the differential diagnosis.     

Follicular dendritic cell sarcoma mimicking giant cell carcinoma of the pancreas

Extranodal follicular dendritic cell (FDC) tumors are rare. Recognition of the morphological spectrum of FDC tumors is important to clinical diagnosis. Herein is presented a case of pancreatic FDC sarcoma with unusual clinicopathological features. A 64-year-old male patient presented with weight loss, poor appetite, abdominal fullness, mild anemia and mild peripheral eosinophilia. Histologically, the tumor was composed of both epithelioid and spindle cells with abundant intracytoplasmic hyaline globules. These tumor cells were positive for CD21, CD23, CD35, S-100 protein, fascin and clusterin. Both epithelioid and spindle tumor cells independently colonized the liver and formed two tumor nodules 18 months after the initial resection. Notably, the two hepatic metastases additionally acquired patchy expression of human leukocyte antigen-DR. The epithelioid FDC in one of the hepatic lesions transformed into numerous bizarre giant cells, which could easily be confused with a metastatic giant cell carcinoma from the pancreas. FDC tumor should therefore be included in the differential diagnoses when dealing with a giant cell tumor.     

Primary hepatic lymphoma with spindle cell components: a case report

Diffuse large B-cell lymphoma (DLBCL) with spindle cell components is extremely rare and often misdiagnosed as carcinoma or sarcoma. Here, we present a case of primary DLBCL with spindle cell components arising in the liver, for which a preoperative diagnosis by needle biopsies was unsuccessful. The patient was a 70-year-old man with a continuous cough. Thoracic computed tomography incidentally detected a mass of 5 cm in diameter in his liver. The initial and second needle biopsies from the liver mass were pathologically diagnosed as suspicious for sarcomatoid hepatocellular carcinoma. He underwent an extended left hepatectomy. Histological examination revealed a diffuse or epithelioid arrangement of round and polygonal cells, mixed with the fascicles of spindle-shaped cells. Immunohistochemically, all the morphological types of tumor cells showed positive reactions for a lymphocytic marker (CD45RB) and B-cell markers (CD20 and CD79a). Double-immunostaining revealed that the spindle-shaped tumor cells expressed CD20, but never expressed alpha-smooth muscle actin. Malignant lymphoma with a spindle cell morphology is quite uncommon, and this variant can be a diagnostic pitfall, especially in tiny biopsy specimens. We emphasize that pathologists should be reminded of lymphoma as a differential diagnosis of spindle cell tumors.     

Malignant perivascular epithelioid cell tumor of the retroperitoneum

Perivascular epithelioid cell tumors (PEComas) are a rare type of mesenchymal neoplasms characterized by a proliferation of perivascular cells with an epithelioid phenotype and expression of myo-melanocytic markers. The majority of PEComas seem to be benign and usually their prognosis is good. Malignant cases are extremely rare, exhibiting a malignant course with local recurrences and distant metastases. We herein report a case of a malignant PEComa arising in the retroperitoneum. The patient was a 55-year-old woman experiencing abdominal discomfort for approximately one month. Ultrasound and computer tomography (CT) scans of the abdomen revealed a solid mass arising from the retroperitoneum. Microscopically, the tumor was composed of epithelioid cells mixed with spindled cells. The nucleus had significant atypia, and the mitoses were obvious. The focal intravascular tumor embolus was visible. Immunohistochemically, the epithelioid tumor cells were positive for HMB45 and Melan-A, and the spindled tumor celLs were positive for SMA and desmin. Seven months after a surgical resection, an ultrasound revealed liver metastases. In conclusion, the malignant PEComas of the retroperitoneum is a very rare neoplasm with unique morphological and immunohistochemical characteristics. It should be differentiated from other epithelioid cell tumors of the retroperitoneum.     

Esophageal pleomorphic giant cell carcinoma combined with small cell carcinoma

Herein is presented the case of an esophageal pleomorphic giant cell carcinoma combined with small cell carcinoma (SCC). The patient, a 77-year-old man, initially presented with dysphagia and hoarseness, and endoscopy indicated a large esophageal tumor. Despite chemoradiation therapy, the patient died from widespread local extension of the tumor and distant metastases approximately 8 months after onset of the symptoms. Histologically, the primary tumor was composed of pleomorphic tumor components, SCC components, and a tiny focus of squamous cell carcinoma. The pleomorphic tumor cells, consisting of solid sheets of poorly cohesive epithelioid cells and numerous multinucleated giant cells with abundant eosinophilic cytoplasm, were immunohistochemically positive for vimentin and desmin, with scattered positivity for epithelial membrane antigen (EMA) and neuron-specific enolase (NSE), but negative for myoglobin. These findings were histopathologically compatible with pleomorphic giant cell carcinoma occurring at other sites such as the lung. SCC cells, morphologically similar to their pulmonary counterpart, were positive for EMA and some neuroendocrine markers such as chromogranin A and NSE, and occasionally positive for vimentin and desmin. Esophageal pleomorphic giant cell carcinoma can occur in close association with SCC, and should be included in the differential diagnosis of esophageal tumors showing pleomorphism.     

Clear cell hepatocellular carcinoma with abundant myxoid stroma.

A case of the clear cell variant of hepatocellular carcinoma with an abundant myxoid stroma is presented. The tumor occurred in a 55-year-old Japanese man, and swelling of the scrotum was the initial symptom. The patient underwent high-level orchiectomy, and the pathologic diagnosis was a metastatic tumor on the surface of the processus vaginalis and intact testis. Extensive examination failed to show a primary site. Subsequent autopsy revealed a large hepatic tumor and metastatic nodules with a prominent myxoid appearance in multiple organs. Histologically, each tumor consisted of uniform small tumor cells with clear cytoplasm attributed to abundant accumulation of glycogen particles, and an abundant myxoid stroma was also present. The tumor cells were positive for keratin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, liver ferritin, prealbumin, and fibrinogen, but lacked alpha-fetoprotein. These findings indicated that this case was hepatocellular carcinoma of the clear cell type with a prominent myxoid stroma.     

Abdominopelvic sarcoma of perivascular epithelioid cells. Report of four cases in young women, one with tuberous sclerosis.

The perivascular epithelioid cell has been proposed to be the unifying proliferating cell type in a number of lesions such as angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumor and renal capsuloma. With the exception of rare examples of angiomyolipoma, they are non-metastasizing. We report four examples of a new member of this family of perivascular epithelioid cell neoplasms that occur in abdominopelvic location and show metastatic properties. The patients, all women, were aged 19 to 41 years (mean, 32), and presented with a tumor mass involving the serosa of the ileum, uterus or pelvic cavity. Morphologically, the tumors were composed of sheets of large polygonal cells with glycogen-rich clear or eosinophilic cytoplasm and moderately pleomorphic nuclei, traversed by a delicate vasculature, mimicking clear cell carcinoma. There were areas of coagulative necrosis and occasional mitotic figures. Intracytoplasmic brown pigment was present in two cases. Spindly cells, smooth muscle and fat were absent. Lymphovascular invasion was present in all, lymph node metastasis was documented in two and metastasis to the ovary was present in one case. Two patients developed widespread metastatic disease after 10 and 28 months from diagnosis. One patient showed the clinical signs of tuberous sclerosis. In spite of the epithelial-like appearance, the tumor cells were negative for epithelial markers but were strongly positive with the melanogenesis-related marker HMB45. Another melanogenesis marker (MART-1) was positive in two cases. Other markers including S-100 protein, vimentin, muscle-specific actin, desmin and chromogranin A were negative. Thus, these tumors are not readily classifiable in the existing schema of known entities, and show overlapping morpho-phenotypic features of clear cell "sugar" tumor of the lung and epithelioid angiomyolipoma. We consider them as sarcomas composed of a pure population of uncommitted perivascular epithelioid cell, that lack modulation toward smooth muscle or adipose cells.     

Epithelioid angiomyolipoma of the liver with striking giant cell component: Fine‐needle aspiration biopsy findings of a rare neoplasm

Angiomyolipoma (AML) is a uncommon benign neoplasm of the liver with cyto‐ and histologic features similar to the more commonly encountered renal AML. Tumors composed predominantly of epithelioid cells have been referred to as epithelioid AML. Because most liver lesions are first evaluated by fine‐needle aspiration biopsy (FNAB), it is important to distinguish this variant of AML from more common hepatic neoplasms such as hepatocellular carcinoma (HCC) or metastatic tumors. Rare reports of epithelioid AML of the liver diagnosed by FNAB are in the literature. Here, we describe the cytologic findings of a unique case of epithelioid AML with numerous giant cells. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

New pathologic entities in penile carcinomas: an update of the 2004 world health organization classification

Most primary malignant tumors of the penis are squamous cell carcinomas (SCC) of the usual type. In recent years several variants, each with distinctive clinicopathologic features, have been described. Pseudohyperplastic carcinoma and carcinoma cuniculatum are both low-grade, extremely well-differentiated SCC variants characterized by an indolent clinical course and good prognosis. The former, which may be confused with pseudoepitheliomatous hyperplasia, preferentially affects the inner foreskin mucosa of elderly men and the latter is a verruciform tumor with an endophytic, burrow-like pattern of growth. Pseudoglandular carcinoma (featuring solid tumor nests with extensive central acantholysis simulating glandular lumina) and clear cell carcinoma (human papillomavirus [HPV]-related tumors composed of periodic acid-Schiff positive clear cells) are aggressive tumors with a high incidence of inguinal nodal metastases. Papillary carcinomas are HPV-unrelated verruciform tumors composed of complex papillae with acanthosis, hyper- and parakeratosis, absence of koilocytes, irregular fibrovascular cores, and jagged tumor base. Finally, in warty-basaloid carcinomas areas of warty (condylomatous) and basaloid carcinomas coexist in the same tumor, either separated or intermingled, giving the tumor a variegated appearance. In this review special emphasis is given to the differential diagnosis of these special variants with a discussion of the possible implications for clinical management.     

Multiple giant angiomyolipomas with a polygonal epithelioid cell component in tuberous sclerosis: An autopsy case report

A recent case of angiomyolipoma (AML) with a prominent Component of polygonal epithelioid cells is described. A 27-yearoid Japanese male with tuberous sclerosis presented with massive abdominal tumors increasing progressively in size. The patient died of respiratory disturbance and the autopsy revealed massive tumors in the bilateral kidneys, liver and lymph nodes, subependymal giant cell glioma of the brain and lymphangiomyomatosis of the lungs. The giant tumors were an unusual type of AML with a component of polygonal epithelioid cells, which showed a hepatocel-lular carcinoma-like pattern in some areas. Smooth muscle components comprising spindle cells, short or plump spindle cells and polygonal epithelioid cells frequently exhibited positive staining for HMB-45 but negative staining for epithelial cell markers. The unusual AML presented in this case was thought to be of low-grade malignancy and slow growing. it has been suggested that angiomyollpomas with diffuse areas of epithelioid cell component are potentially malignant. Immunostalnings positive for HMB-45 but negative for epithelial cell markers are considered to be useful in differentiating AML with polygonal epithelioid cell component from other tumors, especially from renal cell carcinoma and hepatocellular carcinoma.     

A uterine leiomyosarcoma that became positive for HMB45 in the metastasis

Uterine smooth muscle tumors are usually spindle cell lesions, but a minority is composed of epithelioid cells. Foci of clear cells can be found in these latter tumors. Recently, it has been shown that some of these tumors can be positive for HMB45, and some authors have advocated calling these lesions perivascular epithelioid cell (PEC) tumors or PEComas. The case we describe here clearly shows that the so called PEC is just a smooth muscle cell capable of changing its immunophenotype. The patient involved is a 29-year-old black woman who was found to have an epithelioid leiomyosarcoma of the uterus in November 1995. She was treated with a simple hysterectomy and bilateral salpingo-oophorectomy. A metastatic lesion was found in her liver. She, therefore, also received chemotherapy and was free of disease until October 2002, when a recurrent tumor was detected in her spine. After undergoing resection of the lesion at 2 different times, in 2002 and 2003, the patient was treated with radiotherapy and is currently receiving chemotherapy. On microscopic examination, the tumor in the uterus and liver both proved to be an epithelioid leiomyosarcomas that was diffusely positive for smooth muscle actin. Approximately 15% of the cells had clear cytoplasm, but sections from 2 different blocks were completely negative for HMB45. However, although the tumors resected from the spine in 2002 and 2003 showed features similar to those of the uterine neoplasm, but with a lower percentage of cells positive for smooth muscle actin and more clear cells, several of the clear cells were positive for HMB45. To the best of our knowledge, this is the first case of a uterine smooth muscle cell tumor that became positive for HMB45 when it metastasized.     

Hepatocellular carcinoma metastatic to the ovary: a report of three cases discovered during life with discussion of the differential diagnosis of hepatoid tumors of the ovary.

Three cases of hepatocellular carcinoma with ovarian metastases discovered during the patient's life are reported. A 31-year-old woman presented with back pain, and radiographic studies disclosed massive liver enlargement and bilateral ovarian tumors. The second patient, a 38-year-old woman, had an enlarged liver at the time of laparoscopic tubal ligation, and subsequently underwent right hepatic lobectomy for hepatocellular carcinoma. Three months later a left ovarian tumor was detected and a total abdominal hysterectomy with bilateral salpingo-oophorectomy performed. The third patient, a 68-year-old woman, presented with gastrointestinal symptoms and weight loss, and had bilateral ovarian tumors and widespread tumor at laparotomy. Two patients died of their disease at 18 months and 4 years 7 months; the third patient is alive with residual tumor at 7 months. The ovarian tumors, which were bilateral and multinodular in two cases and focally cystic in one case, ranged from 4 to 11 cm in maximum dimension, and had yellow-green or yellow sectioned surfaces. On microscopic examination, they were composed of cells with moderate to abundant eosinophilic cytoplasm growing diffusely and in nodules, nests, and trabeculae; cysts or glands were conspicuous in two cases. Bile was present in one tumor. The main differential diagnostic considerations were hepatoid yolk sac tumor and hepatoid carcinoma, primary or metastatic in the ovary. A variety of features, including the age of the patient, unilaterality or bilaterality of the ovarian tumors, distribution of disease, and microscopic features of the neoplasm, including the identification of bile, established the diagnosis. Metastatic hepatocellular carcinoma must be included in the differential diagnosis of oxyphil cell tumors of the ovary.     

Osteopontin is differentially expressed in renal cell tumors

ABSTRACT

Osteopontin (OPN) has been shown to play a significant role in regulating the aggressiveness of cancer cells and promote tumor growth. Evaluation of this phosphorylated extracellular glycoprotein expression may help estimate its use as a potential prognostic marker in tumorigenesis of different renal tumors. The objective of the present study was to characterize for the first time the expression pattern of OPN in primary renal tumors and correlate its association to tumor progression and survival. A total of 68 primary renal tumors (clear cell renal cell carcinoma, oncocytoma, renal cell carcinoma, invasive urothelial carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, papillary urothelial carcinoma) were analyzed by immunohistochemical staining and Western blot methods. Expression of OPN in relation to grading, histologic type of tumor, and survival was statistically assessed. Study data demonstrated that OPN is differentially expressed in various renal tumor cells types. It was shown that OPN is predominantly expressed at the protein level in clear cell renal cell carcinoma when compared to other types of renal tumors. In conclusion, osteopontin may be involved in the pathogenesis of renal tumors. However, the role of OPN expression in predicting the biological response requires further evaluation.     

血管周上皮样细胞肿瘤的分子遗传学

血管周上皮样细胞肿瘤(perivascular epithelioid cell tumours,PEComas)是由组织学和免疫组织化学上有独特表现的血管周上皮样细胞构成的间叶性肿瘤,PEComas家族包括肾血管平滑肌脂肪瘤、肺透明细胞"糖"瘤、淋巴管肌瘤病、淋巴管平滑肌瘤、镰状韧带透明细胞肌黑色素细胞性肿瘤和其他部...     

Triple synchronous neoplasms in one kidney: report of a case and review of the literature

We report the case of a patient with three synchronous but histologically different primary renal tumors that were all in the same kidney. Two tumors were different subtypes of renal cell carcinoma (RCC), and the third was a variant form of angiomyolipoma. The patient was a 62-year-old man who was receiving antihypertensive drugs and came to our hospital for a regular check-up. Ultrasonography performed during the visit revealed a left renal mass, but the patient had no related symptoms. Subsequent computed tomography revealed two round, high-density masses, one in the mid-portion and the other in the lower pole of the left kidney, and multiple cysts in the right kidney and the liver. The mass in the mid-portion measured 3.3 x 3.0 x 2.8 cm, and the mass in the lower pole measured 1.7 x 1.1 x 0.9 cm. A left radical nephrectomy was performed. On gross examination, an additional ovoid nodule (0.6 cm in the greatest dimension) was found in the lower pole. Microscopically, the largest tumor consisted of a broad alveolar arrangement of large round cells with abundant eosinophilic or clear cytoplasm, distinct cell borders, and perinuclear halos, features consistent with chromophobe RCC. The smallest tumor was a conventional (clear-cell) RCC. The third tumor was composed solely of atypical epithelioid cells with prominent nucleoli and yellowish-brown to black pigments. The tumor cells were positive for melanin (Fontana-Masson stain), the melanoma marker HMB45, vimentin, smooth-muscle actin, and the macrophage marker CD68 and were negative for cytokeratin. This tumor was considered a pigmented epithelioid type of angiomyolipoma. The histologic, histochemical, and immunohistochemical features in this case confirmed the presence of three synchronous primary tumors, a chromophobe and a clear-cell type RCC and a pigmented epithelioid angiomyolipoma, all of which were in the same kidney. This case is the first of its type reported in the literature.     

Fine-needle aspiration cytology of hepatic leiomyosarcoma

Hepatic leiomyosarcoma is a rare malignancy to involve the liver, occurring as a primary liver sarcoma in patients without an underlying medical disorder, as a metastatic malignancy, and with increasing incidence, as a primary tumor in AIDS patients. A series of hepatic leiomyosarcomas diagnosed by FNA biopsy, including the first reported case in an adult AIDS patient, were reviewed with respect to cytomorphologic features. The series consisted of five men and two women ranging from 24 to 72 years of age. One case was a primary hepatic lesion in a 24-yr-old man with AIDS and six were metastatic from a number of sites (stomach, small bowel, retroperitoneum, vena cava, and seminal vesicle). Two cytologic patterns were identified. Aspirates of spindle-cell leiomyosarcomas (six cases) generally produced hypocellular smears composed primarily of small irregular clusters of cells with blunt-ended, uniform, overlapping nuclei. The differential diagnosis included benign reactive processes and other benign and malignant spindle-cell neoplasms. The aspirate of an epithelioid leiomyosarcoma (one case) revealed a second pattern characterized by highly cellular smears with many single polygonal cells having eccentric, malignant nuclei and a characteristic clear quality to the cytoplasm in Papanicolaou-stained material. This epithelial appearance generated a differential diagnosis that included hepatocellular carcinoma, metastatic carcinoma, and melanoma. Careful integration of clinical information, cytomorphologic features, and ancillary studies will allow specific FNA diagnosis of hepatic leiomyosarcoma in most cases. Diagn Cytopathol 1994;11:321–327. © 1994 wiley-Liss, Inc.