Review of mucinous tubular and spindle-cell carcinoma of the kidney with a focus on clinical and pathobiological aspects

Recently, the characterization of mucinous tubular and spindle-cell carcinoma (MTSCC) has been established. MTSCC predominantly occurs in females. This tumor is histologically characterized by eosinophilic cytoplasm, elongated and anastomosing tubules, myxomatous stroma and low-grade nuclear cytology. Proliferation of spindle cells or foci of clear cells are also observed. Histochemically, the myxomatous stroma exhibits a positive reaction for alcian blue and colloidal iron stainings. Ultrastructurally, short microvilli are focally observed and junctional complexes are present. Recently, multiple losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15 and 22 in MTSCC have been elucidated by using comparative genomic hybridization. The prognosis of MTSCC is generally favorable, but some cases may show local recurrence or metastasis. Some cases with MTSCC seem to show overlapping histology with low-grade collecting-duct carcinoma. Therefore, further investigation will be needed to elucidate pathobiological characteristics of MTSCC.     

Renal leiomyoma: an immunohistochemical, ultrastructural and comparative genomic hybridization study

Renal leiomyoma is a rare neoplasm. We report such a case in a 57-year-old Japanese woman who was found to have a mass in the left kidney. The histological examination disclosed the proliferation of spindle cells showing a benign appearance. Entrapped tubular cells were observed in the peripheral area of the tumor. The immunohistochemical examination of spindle neoplastic cells showed a positive reaction for alpha smooth muscle actin, h-caldesmon, l-caldesmon, calponin, muscle actin, myosin and desmin. Additionally, the ultrastructural examination of the tumor showed membrane caveolae and myofilaments in the cytoplasm. This tumor was considered to show a differentiation into smooth muscle cells. The comparative genomic hybridization of the tumor detected the combined losses of chromosomes 4, 6, 12 and 14 which has not been previously described in renal tumors. Finally, the immunohistochemical panel of smooth muscle markers and ultrastructural and genetic study may be useful in diagnosing renal leiomyoma.     

Frequent expression of neuroendocrine markers in mucinous tubular and spindle cell carcinoma of the kidney

Mucinous tubular and spindle cell carcinoma (MTSCC) is a new tumorous entity which has been recently established. In this article, we examined the expression of neuroendocrine markers including neuron specific enolase (NSE), chromogranin A and synaptophysin in 16 cases of MTSCC using immunohistochemistry. The sex ratio (male: female) of the patients was 4:12. In normal kidney, distal tubules or collecting ducts were positive for NSE, but no structures were positive for chromogranin A or synaptophysin. All MTSCCs showed a positive reaction for NSE. Additionally, fifteen of sixteen neoplasms (93.8%) with MTSCC showed the expression of either chromogranin A or synaptophysin or both. Finally, it is possible that MTSCC may be one of renal neoplasms which frequently exhibit the neuroendocrine differentiation.     

Spindle cell lipoma of the oral cavity. Report of a rare intramuscular case with fine needle aspiration findings

BACKGROUND: Spindle cell lipoma (SCL) is a benign neoplasm characterized by a mixture of mature fat, bland spindle cells and wiry collagen in a variably myxoid background. Oral SCLs are rare, and only four cases of intramuscular SCL exist in the literature. We report the first case of intramuscular SCL of the oral cavity with fine needle aspiration (FNA) findings. CASE: A 61-year-old woman presented with a 3-cm mass in the right gingivobuccal sulcus. Papanicolaoustained FNA smears were hypocellular and contained loose collections of spindle cells in a myxoid background, numerous mast cells, rare capillary fragments and portions of skeletal muscle. The spindle cells had mild nuclear enlargement, focal nuclear irregularities, rare intranuclear inclusions and occasional small nucleoli. No lipoblasts or mitoses were identified. There was intermingling of the spindle cells with the skeletal muscle fragments. CONCLUSION: Intraoral SCL is a rare lesion but should be considered in the differential for a benign spindle cell neoplasm in the oral cavity. Clues to diagnosis on cytology include mature fat, bland spindle cells, a myxoid background and mast cells.     

Follicular dendritic cell sarcoma of the cervical lymph node diagnosed on fine needle aspiration cytology

Follicular dendritic cell sarcomas (FDCS) are rare tumours of lymph nodes and extranodal tissues which are grouped with the histiocytic and dendritic cell neoplasms. The diagnosis is usually made after thorough clinical and pathological examination with immunohistochemical analysis. Difficulties persist in diagnosing FDCS on cytological preparations. We report herein a case of a 57-year-old female who presented with a right neck mass of 5 months duration. Computed Tomography (CT) imaging of the neck reported a necrotic right level IIb lymph node and asymmetric fullness of the right palatine tonsil. Fine needle aspiration (FNA) biopsy revealed numerous spindle, oval and stellate neoplastic cells, arranged singly and in syncytia with moderate nuclear pleomorphism, vesicular chromatin pattern, and prominent nucleoli, sprinkled with small lymphocytes. The tumour cells were strongly diffusely positive for CD21, CD23, and D2-40 immunostaining on cell bock sections, but were negative for CD1a and CD34, supporting the diagnosis of FDCS. Follow-up surgical pathology on the resection showed histopathological features and an immunohistochemical profile consistent with FDCS.     

Sarcomatoid acquired cystic disease-associated renal cell carcinoma

In this article, we report a rare case of hitherto undescribed acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) with sarcomatoid change. A 78-year-old woman had been receiving hemodialysis for fourteen years at the time when a renal tumor was encountered on the follow-up examination of the kidney. Microscopically, oncocytic cuboidal cells proliferated with tubular, cribriform or papillary growth patterns, and atypical columnar cells with abundant cytoplasm proliferated with papillary configuration. Oxalate crystal deposition was observed in the stroma and the tumor focally resembled translocation type (TFE3) RCC. Sarcomatous neoplastic cells were also seen. The cytoplasm of oncocytic and sarcomatous neoplastic cells was diffusely positive for anti-mitochondrial antibody and the ultrastructural examination detected many mitochondria in the cytoplasm of oncocytic carcinoma cells and sarcomatous neoplastic cells. The loss of chromosomes 1p, 2q11-22, 9 and 14 was observed using comparative genomic hybridization analysis. We thus report here a case of hitherto undescribed ACD-associated RCC intermingled with oncocytic cells, translocation type RCC-like area and sarcomatoid change. This is the sixth case of sarcomatoid RCC arising in end-stage kidney disease.     

Fine needle aspiration cytology of a dedifferentiated liposarcoma: report of a case with histologic and immunohistochemical follow-up

BACKGROUND: Dedifferentiation is a histologic progression of a neoplasm from low grade to high grade histology. It occurs in tumors of the retroperitoneum and in those undergoing treatment. This usually occurs in the setting of radiation or chemotherapy or as a spontaneous process over a long period. The features of dedifferentiation can be toward any mesenchymal element of the underlying neoplastic process. CASE: We report the cytologic features of a dedifferentiated liposarcoma arising in a 76-year-old man who had a history of well-differentiated liposarcoma. Papanicolaou- and Diff-Quik-stained smears from a radiologically guided fine needle aspiration biopsy showed a hypercellular sample. The smears showed a mixed population of cells. There were multinucleated, pleomorphic giant cells with abundant cytoplasm, smaller clusters of cells with a high nuclear/cytoplasmic ratio and cells with spindled and elongated nuclear features. The follow-up surgical resection specimen showed a dedifferentiated liposarcoma with strong and diffuse immunoreactivity to vimentin, desmin and CD68 in the large, pleomorphic cells; focal and weak immunoreactivity to smooth muscle actin and S-100 in these cells; and strong and focal immunoreactivity to desmin, smooth muscle actin and muscle-specific actin in the spindle cells. This supports the dedifferentiated components of this tumor to be of fibrohistiocytic and leiomyosarcomatous differentiation. CONCLUSION: Dedifferentiation of a well-differentiated liposarcoma should be entertained in the setting of a mass lesion in the retroperitoneum in patients with prior histories of well-differentiated liposarcoma. The radiologic features of a particular neoplastic process can be very helpful in determining the nature of this process.     

Fine needle aspiration cytology of intranodal myofibroblastoma. A case report

BACKGROUND: Intranodal myofibroblastoma is a rare, primitive, mesenchymal neoplasm of the lymph nodes first described in 1989. It behaves in a benign fashion and has a great predilection for the inguinal region. CASE REPORT: A 56-year-old man was referred for fine needle aspiration cytology of an inguinal lymph node. Smears were moderately cellular, with a predominant population of single, small spindle cells with no atypia. Most neoplastic cells were distributed as dissociated, single cells, with few groups. The cells showed metachromatic stromal material with a fibrillary quality. Nuclei were elongated, with pointed ends and occasional twisted forms. A remarkable finding on Papanicolaou-stained smears was hemosiderin granules. After a cytologic report of low grade spindle cell tumor, the node was excised, and a histologic and immunohistochemical diagnosis of intranodal myofibroblastoma was established. CONCLUSION: Intranodal myofibroblastoma should always be considered when aspirating solitary inguinal lymph nodes. The presence of a low grade spindle cell pattern of variably dissociated cells with hemosiderin granules should lead to immunocytochemical studies. Muscle-specific actin expression in the absence of S-100 protein and vascular markers permits a more specific diagnosis.     

Aspiration cytology of fibrosarcomatous variant of dermatofibrosarcoma protuberans with osteoclastlike giant cells in the chest wall: a case report

BACKGROUND: A case of fibrosarcomatous variant of dermatofibrosarcoma protuberans (FS-DFSP) with osteoclastlike giant cells involved the dermis and subcutaneous tissue of the chest wall. This case was misdiagnosed as primary breast tumor clinically and had cytologic features similar to those of the metaplastic breast carcinoma (MRBC). CASE: A 53-year-old female presented with a nodular breast mass enlarging slowly over a long period of time and growing rapidly for about 3 months. The aspirates showed high cellularity with both individually scattered and fascicular arrays of spindle cells. A few multinucleated giant cells without nuclear atypia were intermixed with dissociated spindle cells. There was no epithelial component in the smear. Cytologic evaluation suggested the possibility of a low grade spindle cell sarcoma as well as MBC. Subsequently, the patient underwent modified radical mastectomy, and the diagnosis of FS-DFSP was made. CONCLUSION: Distinguishing FS-DFSP with osteoclastlike giant cells from other spindle cell tumors of the breast, especially MBC showing predominantly spindle cell components, may pose significant challenges to the pathologist. However, clinical and radiologic findings and a meticulous search for other components raised the possibility of FS-DFSP on aspiration cytology.     

Kaposi's sarcoma of the thyroid gland in an HIV-negative woman: a case report

BACKGROUND: Kaposi's sarcoma (KS) is a neoplastic disease that affects primarily the skin, but visceral involvement is not uncommon. Most of the cases are seen in AIDS patients and transplant recipients; however, rare HIV-negative cases have also been reported. Involvement of the thyroid is exceedingly rare, with only a fw cases reported, all of them associated with AIDS. CASE: A 45-year-old, black, Haitian woman presented with a slowly enlarging left side of the thyroid. Computed tomography showed multiple thyroid nodules, and there was no uptake of iodine on the nuclear scan. Fine needle aspiration of the lesion was performed. The smears were composed of spindle and plasmacytoid cells, which raised the possibility of medullary carcinoma. The patient underwent left hemithyroidectomy. Histologic examination showed KS in the thyroid. CONCLUSION: We present the first case of KS of the thyroid in a HIV-negative patient. Familiarity with the cytologic features can be useful in making the diagnosis.     

c-kit immunocytochemical staining in the cytologic diagnosis of metastatic gastrointestinal stromal tumor. A report of two cases

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a distinct group of mesenchymal neoplasms recently shown to exhibit differentiation toward interstitial cells of Cajal (ICC). C-kit (CD117), an immunocytochemical marker consistently expressed in normal ICC, is demonstrable in 81-100% of GISTs. We report two cases wherein immunocytochemical staining for c-kit aided in the diagnosis of metastatic GIST in the liver. CASES: Two patients, a 37-year-old female (case 1) and a 76-year-old male (case 2), presented with multiple nodules in the liver. They had a history of small bowel GIST resected 11 and 1 year earlier, respectively. Fine needle aspiration of the liver nodules showed loose aggregates or fascicles of spindle cells with elongated to oval nuclei, rare paranuclear vacuoles and eosinophilic cytoplasm. The spindle cells showed minimal (case 1) to moderate nuclear pleomorphism (case 2), with occasional mitotic figures seen in case 2. Immunocytochemical staining revealed strong and diffuse staining for c-kit; it was negative for actin, desmin, CD34 and S-100 protein. Thus, a diagnosis of metastatic GIST was rendered. Histologic review of the primary small bowel GISTs of both cases and the subsequently resected liver nodules in case 1 confirmed the diagnosis. CONCLUSION: Metastatic GIST may pose diagnostic problems due to its broad morphologic spectrum and variable cytologic atypia; in particular, distinction from leiomyosarcoma and other mesenchymal tumors is difficult. The diagnostic difficulty is compounded when the prior history of gastrointestinal tumor is not available or forgotten and when GIST is the initial presentation of the tumor. C-kit is a highly sensitive and reliable immunocytochemical marker that can aid in the diagnosis.     

Anaplastic large cell lymphoma presenting as a pleural effusion and mimicking primary effusion lymphoma. A report of 2 cases

BACKGROUND: Systemic anaplastic large cell lymphoma (ALCL) is predominantly a nodal disease, but extranodal involvement can occur during the disease course or as the primary presentation. We report two rare cases of ALCL presenting with a pleural effusion, mimicking primary effusion lymphoma (PEL). CASES: Two patients, a 47-year-old woman and an 81-year-old man, presented with a pleural effusion for investigation. The pleural fluid contained abundant, large, lymphoid cells with marked nuclear atypia. These neoplastic cells strongly expressed CD30 and EMA and showed a T-cell phenotype (CD3+CD45RO+ for case 1 and CD4+ for case 2). Case 1, in addition, showed ALK1 expression. The tumor cells in both cases were negative for human herpes virus type 8 (HHV8) and Epstein-Barr virus (EBV). ALCL shows overlapping cytologic features with PEL, but the T-cell phenotype, ALK1 expression in case 1, lack of association with HHV8 and EBV, HIV seronegativity and subsequent discovery of nodal disease in case 2 were all in favor of ALCL over PEL. CONCLUSION: In rare cases a pleural effusion is the presenting feature of ALCL, and distinction from PEL depends on correlation with clinical findings, detailed immunophenotyping and study of the status of HHV8 and EBV.     

An idic(15) associated with POF (premature ovarian failure): molecular cytogenetic definition of a case and review of the literature

We report on a 36-year-old infertile woman, presenting a premature ovarian failure with an otherwise normal female phenotype. Cytogenetic analyses showed the presence of a supernumerary marker chromosome, that was characterized by FISH (fluorescent in situ hybridization) and array CGH (comparative genomic hybridization). This marker chromosome was derived from chromosome 15, and contained only heterochromatic material. The Prader Willi/Angelman region was not present. No duplications of the 15q regions were detected by array CGH. Supernumerary markers of chromosome 15 have been reported in cases of infertility and amenorrhea, that is also described in cases with marker derived by other acrocentric chromosomes. The case here presented constitutes a further example that etiology of POF is not always associated with a defective gene, but in some cases oocytes atresia can be the consequence of the abnormal meiotic pairing of chromosomes.     

Fine needle aspiration cytology of adult perineal rhabdomyosarcoma: a case report

BACKGROUND: Adult perineal soft tissue sarcomas are rare. Fewer than 30 cases have been reported, and all were diagnosed after surgical resection by histologic examination. Below we report a case in which the diagnosis was established preoperatively by fine needle aspiration (FNA). CASE: A 27-year-old man presented with a firm, midline, perineal mass. Magnetic resonance imaging showed a 3-cm, enhancing mass that was considered neoplastic. FNA biopsy, followed by cytologic examination, revealed moderately cellular aspirates composed of discohesive, small, blue cells with scant cytoplasm, high nuclear/cytoplasmic ratios and pleomorphic nuclei with irregular nuclear contours; uniform, hyperchromatic chromatin; and occasional mitotic figures. Frequent naked nuclei and scattered cells with more abundant, dense cytoplasm and eccentric nuclei were also noted. The diagnosis of rhabdomyosarcoma was favored on FNA and was corroborated by immunohistochemical stains for desmin, myogenin and CD56. Upon surgical resection, the diagnosis of alveolar rhabdomyosarcoma was confirmed histologically and immunophenotypically. CONCLUSION: FNA is a useful tool in diagnosing soft tissue lessions of the perineum, including rare primary tumors, such as adult rhabdomyosarcoma. In this case, early identification avoided incisional biopsy and directed appropriate extirpative surgery and reconstruction considerations.     

Primary pulmonary malignant peripheral nerve sheath tumor: a case report

BACKGROUND: Although the histologic features of malignant peripheral nerve sheath tumor (MPNST) have been described, the cytologic features of primary pulmonary MPNST have not been reported in the literature. CASE: We report a case of primary pulmonary MPNST in a 78-year-old man. Follow-up computed tomography of colon cancer, renal cancer, penile cancer and gingival cancer revealed a nodular lesion, 12 mm in diameter, in the right upper lobe of the lung. In frozen section, a diagnosis of malignant neoplasm, not otherwise specified, was rendered for the imprinting specimen and histologic specimen. Imprinting specimens were composed of small cellular aggregates and discohesive neoplastic cells with obvious malignant features. Histologically, spindle cells with pleomorphic nuclei arranged infascicular patterns and multinucleated tumor giant cells were also observed. More than 25 mitotic figures were observed per 10 high-power fields. Tumor cells were positive only for vimentin and S-100, and the Ki-67 labeling index was 10%. Clinical and imaging investigation failed to identify an alternative primary site. We histologically diagnosed this case as primary pulmonary MPNST. CONCLUSION: MPNST has a varied cytomorphology with frank nuclear atypia showing no definite differentiation. Multinucleated neoplastic giant cells with immunopositivity for S-100 may permit more accurate diagnosis of MPNST.     

肾脏黏液性小管状和梭形细胞癌三例报道并文献复习

目的探讨肾脏黏液性小管状和梭形细胞癌(mucinous tubular and spindle cell carcinoma,MTSCC)的临床病理学特点。方法对3例MTSCC进行光镜、特殊染色、免疫组织化学染色及荧光原位杂交(FISH)检测,并复习临床资料及相关文献。结果 3例MTSCC中,2例为男性,1例女性,年龄分别为50、71、75岁(中位71岁),例2临床表现为腰痛,3例均无肉眼血尿。肿瘤长径分别为2.0cm、3.5cm、6.0cm(中位3.5cm),肿瘤切面灰白色,与周围肾实质界限清晰,例2局部伴出血、坏死。组织学上肿瘤由温和一致的立方细胞紧密排列成狭长的小管结构及梭形细胞两种成分构成,例1、例3部分肿瘤细胞胞质透明,例1黏液性间质稀少;例2、例3间质内见泡沫细胞聚集。免疫表型:3例均表达AMCAR、CK7、CK19、EMA、NSE等,Ki-67低于5%。FISH结果:3例均无乳头状肾细胞癌的染色体异常:3、7、17染色体扩增及Y染色体丢失。结论MTSCC为低级别肾细胞癌,形态学谱系广泛,免疫表型表达远曲小管上皮标记(AMCAR、CK7、CK19、EMA、NSE等),主要需与乳头状肾细胞癌相鉴别,一般预后较好,术后仍须密切随访。     

Validation of a multicolor interphase fluorescence in situ hybridization assay for detection of transitional cell carcinoma on fresh and archival thin-layer, liquid-based cytology slides.

OBJECTIVE: To evaluate the feasibility of performing multicolor interphase fluorescence in situ hybridization (FISH) on ThinPrep slides of transitional cell carcinoma (TCC). STUDY DESIGN: Slides from 20 voided urine specimens were prepared by the ThinPrep technique (Cytyc, Boxborough, Massachusetts, U.S.A.), pretreated using a pretreatment kit and subjected to hybridization with the multicolor FISH probe UroVysion (Vysis, Downers Grove, Illinois, U.S.A.). Archival slides were placed in xylene, destained in alcohol and washed prior to pretreatment. Urines from patients with cytology-positive, biopsy-proven grade 1 (n = 5), 2 (n = 7) and 3 (n = 5) TCC and negative cytology and biopsy (n = 3) were selected. Freshly prepared (n = 10) and archival (n = 10) slides were used. RESULTS: All carcinoma cases were FISH positive (> 5 cells with complex abnormalities of > or = 2 studied chromosomes per slide). None of the normal samples were aneusomic. Gain of chromosomes 3, 7 and 17 constituted the majority of positive cases. Proper destaining and slight decrease in stringency wash conditions enabled reliable detection of signals in archival cases. CONCLUSION: Routine ThinPrep slides can be used for multicolor interphase FISH analysis of urine cytology specimens. Archival slides provide the opportunity to analyze by FISH the nature of atypical cells identified by cytology. This revised method allows FISH technology more accessibility for routine use in cytology laboratories.     

Sarcoma botryoides of the cervix. Report of a case with cytopathologic findings.

BACKGROUND: Cytologic findings of sarcoma botryoides were still equivocal because sarcoma botryoides of the uterine cervix is an extremely rare neoplasm, and few cases have been reported to date. CASE: A 17-year-old female was diagnosed with sarcoma botryoides of the uterine cervix. The entire vaginal canal was occupied with polypoid masses, which arose from the anterior lip of the uterine cervix, and the tumor was classified as group I (Intergroup Rhabdomyosarcoma Study). After wedge resection and six courses of combination chemotherapy, the tumor recurred in the same location of the cervix as the primary lesion. Touch smear of the polypoid mass formed loose clusters and also showed short spindle cells in a necrotic background. The nucleus of the tumor cells had a thin nuclear membrane, fine chromatin pattern and partly clear nucleolus, showing mild nuclear atypia. Immunohistochemically, some of the tumor cells showed positive staining for myoglobin and desmin. CONCLUSION: The cytologic findings of sarcoma botryoides of the female genital tract are typical features of nonepithelial malignant tumor. Immunohistochemical study is useful for the diagnosis of rhabdomyosarcoma.     

Immunostaining characteristics of irisin in benign and malignant renal cancers

ABSTRACT

We investigated the expression of irisin in renal cancers using immunocytochemistry. Irisin has been reported to exhibit anticancer properties. The study groups consisted of 22 cases each of control renal tissue, oncocytoma, chromophobe renal cell carcinoma (RCC), clear cell RCC (Fuhrman nuclear grades 1, 2, 3 and 4) and papillary RCC. We evaluated 10 slides for each of 176 cases. Slides were immunostained for irisin and histoscores were calculated for the prevalence and strength of immunostaining. Fuhrman nuclear grade 1, 2, 3 clear cell RCC and papillary RCC exhibited no irisin immunoreactivity. Irisin immunoreactivity was observed in some Fuhrman nuclear grade 4 RCCs. We found a significant decrease in irisin staining in chromophobe RCC compared to the control. Immunoreactivity in the oncocytoma tissue was comparable to the control group. Irisin immunoreactivity in chromophobe RCC decreased and no immunoreactivity was observed in Fuhrman nuclear grade 1, 2, 3 clear cell RCC and papillary RCC. Immunistochemical screening of irisin in renal oncocytomas and renal cancers may be useful for differential diagnosis.