Use of Electron Microscopy and Other Special Techniques in the Investigation of Suspected Specimen Contamination

Contamination of a biopsy or surgical specimen with spurious tissue is an uncommon but potentially disastrous event. In this regard, the case of a 5-year-old boy referred for treatment of an abdominal tumor is presented. Sections made from paraffin blocks brought by the family showed both neuroblastoma and a spindle cell sarcoma, initially suggesting the possibility of divergent or mixed differentiation. However, the resemblance of the spindle cell component to well-differentiated leiomyosarcoma rather than rhabdomyosarcoma raised the suspicion that a specimen contamination had occurred. Electron microscopy was instrumental in confirming the smooth muscle nature of the sarcomatous component, leading to a fluorescence in situ hybridization study, which established that this component was incompatible with the patient's gender. This case illustrates that even when the light microscopic differential has been compromised by specimen mishandling, electron microscopy can at times provide useful information regarding specimen identity, as well as assist in sorting out the correct diagnosis.     

A case of adenocarcinoma of the lung with a spindle cell component.

We report a 60-year-old man, who was admitted to the hospital with complaints of cough and sputum. His chest x-ray showed an abnormal mass in the right upper lobe. After admission he noticed the painful gingival tumor. Right upper lobectomy and resection of the gingival tumor were performed. Their histological features showed that the tumor consisted of a papillary and tubular adenocarcinoma mixed with a component of spindle cells. Immunohistochemical study demonstrated a positive reaction in the epithelial component for keratin and epithelial membrane antigen, and not only these epithelial markers but also vimentin were expressed in some spindle tumor cells. Electron microscopic study confirmed the biphasic pattern, showing gland formation and undifferentiated cells. We diagnose this case as adenocarcinoma of the lung with a spindle cell component and the gingival tumor was metastatic. Autopsy showed that metastatic lesions were found in the left adrenal gland and in the left kidney. The tumor cells in the left adrenal gland were composed of spindle cells and the tumor in the left kidney showed gland formation. Immunohistochemical and electron microscopic findings of surgical and autopsy specimen suggest that this tumor is of epithelial origin, and the spindle cells are derived from immature mesenchymal cell transformation of epithelial cells.     

Pulmonary carcinomas with a sarcomatoid element: an immunocytochemical and ultrastructural analysis

Eight primary carcinomas of the lung with a prominent spindle-cell sarcomatoid component were studied by immunocytochemical staining and electron microscopy. The eight tumors were indistinguishable by conventional light microscopy, with the exception of one unusual neoplasm that followed multiple pathways of differentiation with elements of squamous cell carcinoma, rhabdomyosarcoma, chondrosarcoma, and an undifferentiated spindle-cell population. Reticulin fiber production by individual spindle cells and a sharp demarcation of the carcinomatous and sarcomatoid domains by light microscopy were not useful differentiating features. Three of the eight tumors exhibited keratin expression in both the carcinomatous and spindle-cell components. Both immunocytochemical and electron microscopic analyses were required to detect epithelial differentiation, as in one case keratin was identified only by immunocytochemical staining and in another only by ultrastructural examination. Epithelial differentiation was undetectable in the sarcomatoid component of five tumors, and in one case immunoreactive myoglobin was identified in spindle cells; skeletal muscle differentiation was confirmed ultrastructurally. We propose that pulmonary carcinomas exhibiting evidence of epithelial differentiation in a sarcomatoid component be termed spindle-cell carcinomas and that those biphasic tumors exhibiting mesenchymal differentiation into specific tissues, such as neoplastic bone, cartilage, or striated muscle, or lacking epithelial differentiation by light microscopy, immunocytochemistry, and electron microscopy be classified as carcinosarcomas. This distinction may ultimately be unnecessary, because these two tumors may represent different points along a morphologic and biologic continuum.     

A Case of Adenocarcinoma of the Lung with a Spindle Cell Component

We report a 60-year old man, who was admitted to the hospital with complaints of cough and sputum. His chest x-ray showed an abnormal mass in the right upper lobe. After admission he noticed the painful gingival tumor. Right upper lobectomy and resection of the gingival tumor were performed. Their histological features showed that the tumor consisted of a papillary and tubular adenocarcinoma mixed with a component of spindle cells. Immuno-histochemical study demonstrated a positive reaction in the epithelial component for keratin and epithelial membrane antigen, and not only these epithelial markers but also vimentin were expressed in some spindle tumor cells. Electron microscopic study confirmed the biphasic pattern, showing gland formation and undifferentiated cells. We diagnose this case as adenocarcinoma of the lung with a spindle cell component and the gingival tumor was meta-static. Autopsy showed that metastatic lesions were found in the left adrenal gland and in the left kidney. The tumor cells in the left adrenal gland were composed of spindle cells and the tumor in the left kidney showed gland formation. lmmunohistochemical and electron microscopic findings of surgical and autopsy specimen suggest that this tumor is of epithelial origin, and the spindle cells are derived from immature mesenchymal cell transformation of epithelial cells. Acta Pathol Jpn 42: 841–846, 1992.     

Spindle cell carcinoma of the breast: A case report and an immunohistochemical study including p53 and Ki-67 expression

A rare case of spindle cell carcinoma (SpCC) of the breast occurring In a 51-yearold Japanese woman Is reported. A firm and well-circumscribed tumor, measuring 9times8.5times8.5 cm, was located on the upper lateral region of the right breast. Microscopically, the tumor consisted of sheets of both malignant spindle cells and poorly differentiated ductal carcinoma containing squamold islands with gradual transition to the spindle cell component. The Immunocyto chemical expression of epithelial markers was recognized in the spindle cells, as well as in the carcinomatous cells. Moreover, the spindle cell component expressed vimentin, α-smooth muscle actln and S-100 protein. Ultrastructurally, in addition to the features of adenocarcinoma, squamous or rnyoeptthelial differentiation was confirmed in the spindle cell component. These findings thus suggest an epithelial origin with squamous differentiations and myoepithellal participation In the genesis of SpCC. In a comparative study, the expression of p53 protein and KI-67 as a proliferation marker In each component of this tumor was also Investigated. The mean p53 labeling index (LI) in both the carcinomatous and spindle cell area was similar, however the mean MIB-1 LI in the spindle cell area was significantly higher than that in the carcinomatous area. The results indicate that p53 over-expression is Involved In the tumorigenesis of both components in the SpCC, and the spindle cell component shows a higher degree of proliferative activity than the carcinomatous component.     

Immunocytochemical investigation of intermediate filament proteins and epithelial membrane antigen in spindle cell tumours of the breast

Seven consecutive cases of primary spindle celled tumours of the breast have been studied immunohistologically using antisera to the intermediate filament proteins (IFP) vimentin, cytokeratin, and desmin, and with an antibody to epithelial membrane antigen. Representative paraffin sections were examined using a peroxidase-antiperoxidase method. In three cases, very occasional foci of epithelial differentiation were apparent by conventional microscopy, and in one case, adjacent ductal carcinoma in situ was present. The remaining three cases were composed of spindle cell elements entirely, with no evidence of epithelial differentiation morphologically. Immunoreactivity of spindle cell elements for vimentin was found in all seven cases, and for cytokeratin in six cases. One case showed immunoreactivity for vimentin, cytokeratin, and desmin, and one case only for vimentin. Epithelial membrane antigen was not identified in the spindle cell elements of any tumour, but was present in the invasive epithelial component of three cases and the in situ component of one case. We conclude that many spindle cell tumours of breast show immunohistological evidence of epithelial differentiation and can be regarded as spindle cell carcinomas. However, in some cases IFP expression may be complex and histogenesis cannot be determined. This technique can aid histological diagnosis in some cases.     

Renal capsuloma: description of a case with predominantly muscular differentiation

The Authors report a case of Renal Capsuloma with a histologic biphasic pattern constituted of epithelioid and spindle cells. The lesion is observed in a nephrectomy specimen as incidental finding concurrent with a Papillary Transitional Cell Carcinoma of calices and renal pelvis. The lesion presents a distinct muscular immunophenotype (actin+, desmin+), with coexpression of the melanogenesis marker (HMB45+) in a lower cellular population. This combined immunophenotype is a characteristic feature of the Perivascular Epithelioid Cell's (PEC) lesions. Actually Renal Capsuloma is a PEC's lesion (Pecoma) closely related to Angiomyolipoma (AML). Particularly Capsuloma is thought as a variant of AML predominantly composed by muscular spindle cells (monotypic spindle cell-leiomyoma like variant of AML). In the presented case the spindle cell component is associated with an epithelioid cellular population which also shows a distinct muscular differentiation. The Authors have not found in the literature the association between Renal Capsuloma and Papillary Transitional Cell Carcinoma of the renal pelvis.     

Sarcomatoid carcinoma with small cell carcinoma component of the urinary bladder: a case report with review of the literature

Sarcomatoid carcinoma of the urinary bladder is an uncommon neoplasm characterized histopathologically by the presence of malignant spindle cell and epithelial components. Albeit extremely rare, sarcomatoid carcinoma with small cell carcinoma has been reported. Herein, we describe an additional case of sarcomatoid carcinoma with small cell carcinoma and squamous cell carcinoma of the urinary bladder and review the clinicopathological features of this type of tumor. An 82-year-old Japanese male presented with hematuria. Computed tomography demonstrated a large tumor in the urinary bladder. Histopathological study of the resected urinary bladder tumor showed that approximately 80% of the tumor was comprised of small cell carcinoma, and the remaining components were spindle cell proliferation (approximately 15%) and squamous cell carcinoma (5%). Both the spindle cell and squamous cell carcinoma components were intermingled with nests of the small cell carcinoma. This is the fifth documented case of sarcomatoid carcinoma with small cell carcinoma of the urinary bladder. Our review of the clinicopathological features of this type of tumor revealed that: i) elderly males are mainly affected, ii) the most common chief complaint is hematuria, iii) the epithelial component may include urothelial carcinoma, adenocarcinoma, and/or squamous cell carcinoma, and iv) the sarcomatous component is composed of spindle cell proliferation. The histogenesis of this type of tumor remains a matter of controversy. However, recent molecular analyses demonstrated a monoclonal origin of both components. This theory can account for the various types of carcinomatous components in this tumor as seen in the present case.     

Gemischter Epithel- und Stromatumor der Niere

We describe a case of mixed epithelial and stromal tumor of the kidney. The tumor was identified in a 63 years old woman and retroperitoneoscopically resected. Immunohistochemistry, electron microscopy and fluorescence in situ hybridization were performed. Grossly, the tumor was well-circumscribed with a diameter of 8 cm and consisted of solid and cystic components. Microscopically, the spindle cell component ranged in appearance from scar-like fibrous tissue to leiomyoma-like fascicles. Epithelial elements were composed of tubules with variable lining. The tubules were focally transformed into large cysts. Estrogen and progesteron receptors were detected in the nuclei of the spindle cells. Electron microscopy confirmed a smooth-muscle differentiation of the spindle cells. Previously, such tumors were published as adult mesoblastic nephroma or cystic hamartoma of the renal pelvis. Its predominance in females with a history of long-term estrogen replacement or the history of long-term sex-steroid use in a male patient, combined with the expression of estrogen und progesteron receptors in the spindle cells suggest that hormonal influence is relevant for the development of these tumors.     

Spindle basaloid squamous carcinoma of the upper aerodigestive tract: immunohistochemical and clinicopathological study of three cases

We describe the clinicopathological and immunohistochemical features of three spindle (sarcomatoid) basaloid squamous carcinomas in three men aged 73, 69, and 59 years with a history of tobacco and alcohol abuse. Two tumors were located in the hypopharynx and one was located in the nasal cavity. The three tumors have a pedunculated polypoid appearance. Histologically, they were composed of conventional basaloid squamous carcinomas with extensive malignant spindle cell proliferation, comprising more than 50% of the tumor. The sarcomatoid component demonstrated immunoreactivity with one or more epithelial markers. One case in addition expressed CD99 and Bcl-2 and was originally diagnosed as monophasic synovial sarcoma; however, a subsequent biopsy disclosed basaloid squamous cell carcinoma with sarcomatoid stroma. Two patients were treated with surgery and radiation whereas one refused therapy. The patients were alive 14 (case patient 1), 10 (case patient 2), and 8 (case patient 3) months after diagnosis. In the absence of evidence from immunohistochemical or electron microscopy studies, a polypoid malignant spindle cell tumor of a mucosal surface of the upper aerodigestive tract should be considered a sarcomatoid carcinoma until proven otherwise. The type of epithelial component would determine the subtype of sarcomatoid carcinoma.     

Synovial sarcoma. Inter-relationship of the biphasic and monophasic subtypes.

In order to assess minimum diagnostic criteria for synovial sarcoma, particularly the monophasic variety, and the inter-relationship between the monophasic and biphasic types, 32 examples were studied histologically, immunohistochemically (26 cases), and ultrastructurally (13 cases). Of the six biphasic synovial sarcomas examined by electron microscopy, the spindle cell component did not show evidence of epithelial differentiation or resemble the epithelial phase, but did appear fibroblastic; no tumor cells transitional between the spindle and epithelial component were evident. In contrast, all of the seven monophasic lesions had ultrastructural growth patterns and some cellular features approximating the epithelial cells of the biphasic variant. In 11 biphasic synovial sarcomas, epithelial membrane antigen was detected in the glandular epithelium of all cases and cytokeratins in eight cases; in no case were these antigens detected in the spindle cell regions of biphasic lesions. Of the 15 monophasic synovial sarcomas, two were positive for cytokeratins and four for epithelial membrane antigen. Thus, the detection of epithelial markers either immunohistochemically or by electron microscopy (or both) should be the minimal diagnostic criteria for monophasic synovial sarcomas. Based on these findings, it is suggested that monophasic synovial sarcomas do not represent the spindle cell or "stromal" phase of biphasic synovial sarcomas, but are a poorly differentiated variant of the latter. As others have suggested, these tumors are, in fact, carcinosarcomas and carcinomas of the soft tissues and the designation synovial sarcoma is inappropriate for this tumor class.     

Papillary carcinoma with nodular fasciitis-like stroma--a case report in pregnancy

We report a case of Papillary carcinoma with nodular fasciitis-like stroma that is a rare variant of Papillary carcinoma characterized by a prominent stromal cell proliferation that causes difficulties in cytologic and histologic diagnosis. The patient was a 34-year-old woman, pregnant, presented with a 1-year history of a growing mass in neck, dysphagia, and hoarseness. Physical examination revealed a firm nodular mass in thyroid gland. The fine needle aspiration biopsy specimen contained, besides diagnostic epithelial features of Papillary thyroid carcinoma, discohesive arrangement of bland spindle cells. Macroscopically, the specimen consisted of nodular tumor measuring 10 x 6 x 6 cm. Histologically the tumor was composed of small foci of neoplastic epithelial component distributed in abundant stroma. In immunohistochemistry, spindle cells in the stroma were positive for alpha-smooth muscle actin and the neoplastic cells showed positive staining for TTF-1 and progesterone receptor.     

Prostatic stromal sarcoma with rhabdoid features

Rhabdoid tumors have been reported in many different anatomic sites as an aggressive tumor and usually present with a rhabdoid tumor component (a composite tumor) rather than a pure rhabdoid tumor. Rhabdoid tumor in the prostate has been described only once in the prostatic region as a possible epithelial origin. Rhabdoid features in prostatic stromal sarcomas (PSSs) have never been described in the literature. Here, we report a case of a PSS with rhabdoid features. A 31-year-old man presented with a 4-month history of voiding difficulty and anal pain. Computed tomography of the abdomen revealed an ovoid mass in the prostate invading rectum and urinary bladder. A needle biopsy was diagnosed as an unclassified spindle cell sarcoma, and 2 cycles of adriamycin-based neoadjuvant chemotherapy were given, followed by radical prostatectomy. The prostatectomy specimen revealed a high-grade sarcoma with fascicles of highly cellular spindle cells and numerous mitoses with hemorrhage and necrosis. In areas, the tumor also contained sheets of loosely cohesive epithelioid cells with rhabdoid tumor component. Both spindle and rhabdoid tumor cells were positive for vimentin, CD34, and progesterone receptor and negative for desmin and cytokeratin immunostainings. The rhabdoid tumor cells retained INI1 expression. The tumor recurred in the bladder, and the patient died of sepsis. To the best of our knowledge, this is the first case of PSS with rhabdoid features. The tumor showed an aggressive clinical behavior with a short-term survival (7 months after diagnosis).     

Basaloid squamous carcinoma with a spindle cell component and osseous metaplasia presenting as a polyp of the hypopharynx

We report a case of basaloid squamous carcinoma with a spindle cell component of the hypopharynx, in a 61-years-old-man. An excisional biopsy of a pedonculated and polypoid tumour was performed by endoscopy. The histologic examination revealed a biphasic tumour with both a basaloid carcinomatous and a spindle cell component. Focally, osseous metaplasia was seen. The spindle cell component demonstrated immunoreactivity with the p63 epithelial marker. The patient was treated with chemotherapy followed by radiotherapy. The patient has been free of disease for one year. It's the ninth case reported in the literature of a biphasic carcinoma with both a basaloid squamous and a spindle cell component and the first case with osseous metaplasia.     

Monophasic synovial sarcoma–a histological entity?

Consideration is given to the concept of a histologically identifiable monophasic type of synovial sarcoma. It is accepted that a sarcomatous tumour may be encountered where the spindle cells assume a somewhat epithelioid appearance associated with a reticulin pattern unlike that of most other spindle cell sarcomas. The appearance should alert a hsitopathologist to the possibility of a synovial sarcoma and prompt the examination of multiple additional sections in an attempt to find the pathognomonic biphasic pattern. It is not, however, believed that an entire tumour composed of cells of a single type could be identified with certainty as a synovial sarcoma by light microscopy. The term monophasic synovial sarcoma is worthy of retention, but only as a guide towards the establishment of a definite diagnosis by further sampling of the specimen. Other features suggestive of this diagnosis are discussed.     

Myopericytoma-type perivascular myoma located in the soft tissue of the foot: a case report and review of the literature

We describe a rare case of myopericytoma-type perivascular myoma (MTPM) which arose in acral location and the literature on this field is briefly reviewed. The patient, a 68-year-old man, presented with an enlarging painful nodule, 1.4 cm across, located in the subcutaneous tissue of the right foot. The patient is alive and well 17 months after surgical excision of the nodule. Microscopically, the lesion was well-circumscribed and characterized by a biphasic pattern with a concentric perivascular spindle and ovoid cell proliferation and an extensive hemangiopericytomatous growth component. Immunohistochemically, the neoplastic cells were positive for vimentin, smooth muscle actin, desmin and calponin, negative for S-100 protein, CD34, CD31 and cytokeratins (AE1/AE3, Cam 5.2). Electron microscopy showed electrondense cell bodies suggestive for myopericytic differentiation. The clinico-pathological features of the present case are similar to those previously reported in the literature and we also discuss herein the main histological criteria for the differential diagnosis with other spindle cell and vascular lesions of soft tissues.     

Cytologic diagnostic pitfall of dermatofibrosarcoma protuberans masquerading as primary parotid tumor: A case report

We report the cytology of a rare case of dermatofibrosarcoma protuberans (DFSP) involving the parotid region. Our patient was a 55‐year‐old female who presented with a swelling in the right parotid region, which was clinically interpreted as a “recurrent parotid tumor.” Fine needle aspiration revealed a moderate cellular yield with spindle cell component, seen discretely as well as, embedded loosely within a fibrillary magenta matrix. A few cellular spindle cell fascicles and several discrete, naked, spindly nuclei were also noted. Neoplastic cells exhibited a minimal pleomorphism with a relatively bland chromatin and inconspicuous nucleoli. A differential diagnosis of the benign spindle cell tumor/low, or intermediate grade myxoid, spindle cell sarcomas was considered. Owing to its clinical presentation simulating a parotid tumor, possibility of “spindle cell myoepithelioma” was suggested. However, histopathologic examination with immunohistochemistry showed it to be a DFSP. A precise diagnosis of DFSP is not always possible on cytology alone. Owing to its location, as well as the spindle cell morphology, DFSP occurring in the parotid region is likely to be mistaken for a spindle cell myoepithelioma, in which case, an appropriate panel of immunomarkers is required for resolving the diagnostic dilemma. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Clear cell renal cell carcinoma with smooth muscle stroma

A recent publication described 5 unusual clear cell renal tumors with prominent smooth muscle stroma that were characterized only by immunostaining. We report 3 additional tumors composed of clear cell renal cell carcinoma intimately admixed with abundant smooth muscle stroma. Epithelial differentiation of the malignant clear cell components and smooth muscle differentiation of the benign spindle cell stroma was confirmed by the immunostaining profiles and by electron microscopy. Fluorescence in situ hybridization analysis of chromosome 3 showed loss of the entire chromosome in 2 cases and loss of 3p in the third case. We therefore interpret these tumors as unique low-grade variants of clear cell renal cell carcinoma that have induced a prolific metaplastic stromal reaction. Extensive tissue sampling and immunostaining are recommended to distinguish cases with an extensive smooth muscle component from morphologically similar but benign lesions including angiomyolipoma, leiomyoma, or mixed epithelial and stromal tumor of the kidney.     

Combined large cell neuroendocrine carcinoma and spindle cell carcinoma of the lung

We report a unique case of a combined pulmonary large-cell neuroendocrine carcinoma and spindle-cell carcinoma. The patient was a 54-year-old female smoker who presented with a 4-month history of increased left-sided chest pain and exertional dyspnea. The left upper lobectomy specimen revealed an 8.0-cm mass with central necrosis. Microscopically, the epithelial areas were composed of well-defined nests of large cells with peripheral palisading expressing low-molecular-weight keratin, synaptophysin, chromogranin, and neuron-specific enolase. The spindle-cell component consisted of pleomorphic cells arranged in fibrosarcoma and malignant fibrous histiocytoma-like patterns. These spindle cells were positive for low-molecular-weight keratin and vimentin with focal expression of CD68 and muscle-specific actin. Electron microscopy in the spindle-cell areas showed cell junctions and numerous tonofilaments, indicative of epithelial differentiation. The tumor behaved aggressively and the patient died with extensive metastases 4 months after surgery. The combination of neuroendocrine malignancies and spindle-cell carcinomas appears to be uncommon in the lung. Previous reports have described this association in single case reports of anaplastic small-cell carcinoma and atypical carcinoid, but not in large-cell neuroendocrine carcinoma.     

Choroidal melanoma diagnosed by aspiration cytology: A case report with cyto-histologic correlation and review of the literature

Histologic and cytologic features of uveal melanomas have been well characterized; however, cytologic-histologic correlation has rarely been described in detail in the literature. A 50-year old female presented at our institution with an intraocular mass which was diagnosed as choroidal melanoma by aspiration cytology. The patient subsequently proceeded to enucleation, confirming the diagnosis. Cytology revealed epithelioid cells containing melanin pigment and only mild nuclear atypia. The enucleation specimen contained 90% epithelioid cells with similar cytomorphology and an additional 10% spindle cell component not observed in the aspiration cytology. In summary, we present a case of choroidal melanoma showing high concordance between cytologic and histologic morphologic features.