Sarcomatoid Adrenal Carcinoma: Case Report with Contribution to Pathogenesis

A tumor in the adrenal region with two metastases in the liver was classified as poorly differentiated sarcoma on the base of extensive immunostainings (expression of vimentin, desmin, myogenin, and CD31, no expression of inhibin, melan A). Four years later in a second examination with molecular methods for a study of adrenal sarcomas, this diagnosis must be revised due to the lack of MDM-2 gene amplification and FKHR translocation which exclude sarcoma. Further immunostainings of many other parts of the tumor showed in one area more mature tumor tissue expressing synaptophysin, SF-1, and melan A. From these findings we classified an adrenal cortical cancer with predominant dedifferentiation into a sarcomatoid adrenal carcinoma. The properties of this very rare cancer type are presented and discussed.     

A case of Sj?gren's syndrome associated with inflammatory pseudotumor of the liver]

A 71-year-old man had noticed a dry sensation in the mouth with swelling of bilateral parotid glands in 1988. He was given a diagnosis of Sj?gren's syndrome (SS) on the basis of characteristic findings of sialography and a minor salivary gland biopsy. He was admitted to our department in Febuary 1995 because of general fatigue of 2 month's duration. Laboratory data showed both positive anti-SSA and anti-SSB antibodies, liver dysfunction, hypoalbuminemia, and thrombocytopenia. Abdominal CT and MRI demonstrated a 2-cm intrahepatic mass (S 6) with enhanced areas at the periphery. The liver biopsy yielded fragments from the intrahepatic mass and hepatic parenchyma. The former was composed of plasma cells, lymphocytes, and histiocytes, compatible with the diagnosis of inflammatory pseudotumor of the liver. The pathological diagnosis of the latter specimen was primary biliary cirrhosis, although antimitochondrial antibody was negative. The intrahepatic mass gradually decreased in size without treatment. Inflammatory pseudotumor is considered to be a benign inflammatory condition simulating a neoplasma and the possibility of an autoimmune reaction is suggested on the basis of etiology. This is the first report of an inflammatory pseudotumor associated with Sj?gren's syndrome developing in the liver. The inflammatory pseudotumor should be considered as a possible diagnosis in cases where the tumor is embedded in the liver.     

Adrenocortical carcinoma: diagnosis by fine needle aspiration cytology

Two cases of adrenal cortical carcinoma are described, wherein the diagnosis was established by fine needle aspiration cytology (FNAC). FNAC is increasingly being accepted as a means of diagnosis of adrenal cortical carcinomas. In yester years the diagnosis was established largely on post-operative histopathology. Adrenal cortical carcinomas are rare and account for less than 0.05% of all malignant neoplasms. Adrenal gland has become frequent target of needle biopsies with the availability of sensitive imaging techniques and better localization. Currently, needle biopsy is the only non-surgical means of obtaining a diagnosis in patient with adrenal mass. We present two cases of adrenal cortical carcinoma diagnosed on fine needle aspiration cytology (FNAC).     

Cytopathology of a primary follicular dendritic cell sarcoma of the liver of the inflammatory pseudotumor-like type

Follicular dendritic cell (FDC) sarcoma is an exceedingly uncommon tumor of lymph nodes and extranodal tissues. The inflammatory pseudotumor (IPT)-like variant of FDC sarcoma of intraabdominal location is considered a separate entity, with different clinical and pathological features than those of the classic FDC tumor. There have been only 12 cytological reports of FDC sarcomas in the literature. Two of them were metastases to the liver and, like our case, had features of IPT. Fine-needle aspiration biopsy (FNAB) and imprint and scrape cytology from the surgically excised tumor here reported revealed spindle tumor cells with moderate pleomorphism, nuclear grooves, prominent nucleoli, and cytoplasmic processes, admixed with inflammatory cells. To the best of our knowledge, this is the first cytology report of a primary hepatic FDC tumor. The cytological findings permit the recognition of this tumor. However, confirmation by inmunohistochemistry (IHQ) is mandatory for a definitive diagnosis.     

眼睑皮脂腺癌的穿刺细胞学诊断及鉴别诊断

目的 探讨眼睑皮脂腺癌的穿刺方法、细胞学特点和鉴别诊断。方法 4例眼睑肿物行细针穿刺细胞学(FNAC)检查,穿刺涂片行常规HE染色以及脂肪染色(苏丹Ⅲ染色),光镜观察其细胞学特点;与活检结果对照,并与霰粒肿、眼睑毛母质瘤和基底细胞癌的细胞学特点进行比较。结果 4例肿物穿刺结果考虑为皮脂腺癌。涂片内细胞丰富,特征明显,可见2种肿瘤细胞,一种为胞质丰富呈泡沫样的皮脂腺分化细胞,一种为核大深染、异型明显的低分化癌细胞,脂肪染色显示肿瘤细胞胞质内及背景中可见橘红色脂滴。穿刺诊断与活检结果基本一致。而霰粒肿细胞学表现为肉芽肿性炎症,毛母质瘤内见无异型的基底样细胞、嗜碱性细胞、影细胞及钙化,基底细胞癌表现为核致密深染、排列紧密的细胞团,与皮脂腺癌易于区别。结论 眼睑肿物穿刺细胞学检查是一种安全有效的检查方法,有助于眼睑皮脂腺癌的早期诊断及答别诊断。     

Fine‐needle aspiration biopsy of pleural metastases from a carcinosarcoma or true malignant mixed tumor of the parotid gland mimicking a mesothelioma

Malignant mixed tumor of the parotid is known to have odd sites for metastases. We describe the fine‐needle aspiration cytology (FNAC) findings of pleural metastasis from a malignant mixed tumor misdiagnosed as a mesothelioma on cytology at the onset. A 47‐year‐old man presented to us with breathlessness and a massive pleural effusion with pleural‐based nodules. He had been operated 2 years before for a pleomorphic adenoma of the parotid and had a healthy scar at that site. FNAC from the pleural lesions showed myxoid background substance with entrapped cuboidal epithelial cells with atypical nuclei, which were interpreted as mesothelial cells. These cells in contrast to the usual mesothelial cells were not arranged in sheets but rather were huddled in places and formed a pseudoacinar pattern and blended with the myxoid substance. After the diagnosis of a mesothelioma, patient received pemetrexed and cisplatin based chemotherapy with partial response. While on chemotherapy tumor recurred at the primary site in parotid and was confirmed to be a carcinosarcoma on a FNAC and biopsy. To conclude, pleural metastases from a true malignant mixed tumor of the parotid gland can be misdiagnosed as mesothelioma and could occur in the absence of uncontrolled disease at primary site. Both mesotheliomas and pleomorphic adenomas metastatic to the pleura are biphasic tumors, but in a patient with history of pleomorphic adenoma, the latter should be kept as a foremost possibility. Attention to the cytomorphology of tumor cells will also assist in confirming the diagnosis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

A103 immunostaining in the diagnosis of adrenal cortical tumors: an immunohistochemical study of 316 cases

CONTEXT: The monoclonal antibody A103 recognizes an antigen on melanoma cells known as Melan-A or MART-1. Recent studies have shown that A103 also reacts with adrenal cortical cells and may be useful in the diagnosis of adrenal cortical tumors. However, only small numbers of some of the tumors in the differential diagnosis of adrenal cortical neoplasms have been studied. OBJECTIVE: To study the specificity of A103 immunohistochemistry in a large number of tumors in the differential diagnosis of adrenal cortical neoplasms. DESIGN: Formalin-fixed, paraffin-embedded tissue from 21 adrenal cortical tumors, 16 cases of metastatic carcinoma to the adrenal, 10 pheochromocytomas, and 269 extra-adrenal carcinomas was evaluated for A103 immunoreactivity using a commercially available antibody (Novocastra, Newcastle, UK). RESULTS: Positive staining was seen in all of the adrenal cortical tumors but in none of the adrenal metastases or pheochromocytomas. In the 269 extra-adrenal carcinomas, A103 immunoreactivity was limited to a single ovarian serous carcinoma. CONCLUSION: A103 immunostaining is useful in distinguishing adrenal cortical neoplasms from other carcinomas and pheochromocytoma.     

Pleomorphic liposarcoma with liver metastasis diagnosed by combined fine-needle aspiration cytology and core-needle biopsy

Pleomorphic liposarcoma (PLPS) is the rarest liposarcoma subtype, with high-local recurrence and metastasis rates. Fine-needle aspiration cytology (FNAC) is successfully used in the diagnosis of primary or metastatic soft tissue tumors, but liver metastases of PLPS diagnosed by FNAC have never been reported. The cytological diagnosis depends on the identification of lipoblasts with sharply defined cytoplasmic vacuoles indenting and distorting the nucleus in the context of a pleomorphic tumor and in a proper clinical and imaging context. Despite its aggressive behavior, hematogenous liver metastases are rare, with just one case reported in literature. A case of PLPS liver metastasis and concomitant primary tumor diagnosed by FNAC and core needle biopsy is herein described.     

Fine-needle aspiration cytology diagnosis of metastatic nonhaematological neoplasms of the breast: a series of seven cases

Metastatic neoplasms of the breast are rare. Mammary metastases as the initial presentation are even more infrequent and can simulate a primary malignancy clinically and radiologically. Recognition of metastatic tumors in the breast is important because it would prevent unnecessary mutilating surgery and would lead to appropriate treatment of the primary tumor. There is a broad variety of cytological appearances reported about primary tumors and few reports about secondary breast malignancies, specially diagnosed by FNAC. This study was carried out to examine the clinical and cytomorphologic features of metastatic breast tumors found in 12 de Octubre University Hospital during a period of 20 years. It confirms the utility of FNAC and describes findings that can help in the differential diagnosis that sometimes can be very difficult. Seven cases of nonhematological metastatic neoplasms of the breast were identified from the files of the Department of Pathology of the 12 de Octubre University Hospital from a total of 64,000 aspirates. We included only metastatic tumors from extramammary nonhematological neoplasms. There were nine cases of hematological metastatic neoplasm that were excluded. They were diagnosed with FNAC and confirmed by histopathology, with at least three years of follow up. The breast lump was the first manifestation of malignancy in one case of synovial sarcoma. The other six cases had been previously diagnosed of cancer. These included one malignant melanoma, one alveolar rhabdomyosarcoma, one mixed müllerian tumor, one medullary carcinoma of thyroid, one colonic adenocarcinoma, and one gastric adenocarcinoma. The period of time between primary tumor and metastases ranged from one month to eight years. An accurate cytologic diagnosis was made in all the cases. Immunocytochemistry was available but diagnosis could be made with cytomorphology alone in the seven cases. Fine-needle aspiration cytology is an excellent first line diagnostic modality that is particularly informative when clinical previous data are known. If metastatic disease is suspected, the material obtained by FNAC may provide a definitive diagnosis and prevent open surgical biopsy or mastectomy. We concur with previous reports that FNAC is a reliable, rapid, secure, and cost-effective approach to the diagnosis of palpable metastatic breast tumors.     

Large cell neuroendocrine carcinoma of the maxillary sinus on fine needle aspiration cytology: Report of a rare case with a focus on pitfalls in diagnosis

Head and neck large cell neuroendocrine carcinoma (LCNEC) is a rare high‐grade malignant tumor with neuroendocrine differentiation. We report a case of LCNEC causing difficulty in cytological diagnosis. A 60‐year‐old man with right‐sided face pain presented with a swelling at the right cheek, and he complained of right nasal obstruction and lacrimation. Preoperative fine‐needle aspiration cytology (FNAC) showed high cellularity, with a moderate number of clusters of tumor cells on an abundant necrotic background. The clusters were arranged in sheet structures with palisading, and were cohesive with overlapping. The tumor cells had comparatively abundant cytoplasm, with conspicuous large, irregular nucleoli with a fine granular chromatin pattern. Mitotic figures were observed easily. On immunocytochemistry using LBC smear, tumor cells were negative for p40. High‐grade carcinoma other than non‐keratinizing squamous cell carcinoma was suggested from these findings on FNAC. The pretreatment histological biopsy sample revealed tumor cells with solid growth pattern, necrotic materials and large polygonal cells with abundant cytoplasm, fine granular chromatin, and conspicuous nucleoli. Head and neck LCNEC with abundant cytoplasm, fine granular chromatin patterns, prominent nucleoli, and necrotic background were very characteristic of LCNEC. If considered carefully, these findings can enable us to exclude the majority of non‐keratinizing squamous cell carcinomas, and FNAC using ancillary technique can be very useful for proper diagnosis.     

Is fine needle aspiration cytology (FNAC) useful in skin adnexal masses? A study on 5 cases of pilomatixoma

Superficial cutaneous/subcutaneous nodules, caused by a variety of inflammatory, benign and malignant pathology of diverse origin, are tempting lesion for fine needle aspiration cytology (FNAC). Amongst these, adnexal tumor show considerable overlap, both in clinical manifestation as well as in histopathology. Archieval records of clinical findings, FNAC smears and reports pertaining to 5 histologically proved cases of pilomatricoma (PMX) were analyzed. Different cytological findings were graded + to +++. Pre FNAC clinical diagnoses were sebaceous cyst, tuberculous lymphadenopathy, dermatofibroma, reactive lymphadenopathy and lipoma. PMX was diagnosed on FNAC in 3 cases on finding groups of basaloid cells, ghost epithelial cells, pink fibrillary material and calcium deposits. Other cases were diagnosed as epidermal inclusion cyst with the differential diagnosis of well differentiated squamous cell carcinoma and skin appendageal tumor of undetermined origin in one case each. In all the cases, FNAC established epithelial nature of the lesion, excluding clinically mimicking inflammatory/neoplastic lesions of other origin. FNAC should be followed by excision biopsy to accurately type the epithelial neoplasm.     

Fine needle aspiration biopsy of the adrenal gland: Cytological features and clinical applications

The ability to visualize the adrenal glands with modern imaging techniques has improved our detection of small adrenal masses. In cancer patients, metastatic tumors to the adrenal glands are common, but not all adrenal masses are metastases. Percutaneous fine needle aspiration biopsy can be used in distinguishing metastatic malignancies to the adrenal glands from primary adrenal lesions. In our series we achieved a success rate of 86% in obtaining cellular material for diagnosis. A diagnosis of metastatic malignancy obviates the need for surgical intervention and is essential for staging and therapeutic planning. Primary adrenal cortical masses with benign cytology and under 5 cm in size can be managed conservatively with follow-up scans; those with atypical cytology or greater than 5 cm in size warrant surgical exploration. Adrenalectomy is the treatment of choice for any adrenal tumor associated with endocrine abnormality, irrespective of tumor size and cytology.     

A small adrenocortical carcinoma with aggressive behavior. An evaluation of criteria for malignancy

Adrenocortical carcinoma is an unusual tumor that tends to be larger than 100 g at diagnosis. Malignant adrenocortical tumors of less than 50 g have been reported rarely. We studied a small adrenocortical carcinoma that weighed 40 g and metastasized 3 1/2 years following bilateral adrenalectomy. The malignancy of adrenocortical tumors is frequently difficult to determine. Two recent studies have proposed histologic criteria for determining the malignancy of adrenal cortical tumors. Since the tumor we studied was initially judged to be benign, we sought to determine whether an extensive evaluation of this tumor using these recent criteria could have identified the tumor's potential for metastasizing. Careful application of these criteria indicated that the tumor was either a borderline lesion or a definitely malignant lesion. This emphasizes the need to approach systematically all adrenal neoplasms with regard to determining their malignant potential. Documenting small adrenocortical carcinomas also should help in setting criteria for evaluating adrenal masses discovered incidentally by sensitive radiologic methods.     

Atypical adenoma of the thyroid diagnosed as anaplastic cancer by cytopathology

Atypical adenoma of the thyroid is a rare form of tumor, and its accurate diagnosis prior to surgical resection is difficult as the histological and pathological morphologies are very similar to those of anaplastic thyroid carcinoma (ATC), and its anaplastic transformation remains to be elucidated. We reported a case of a 75‐year‐old female with a thyroid isthmus nodule diagnosed repeatedly by FNAC as anaplastic carcinoma. Both the first and second FNAC specimen slides showed a large number of scattered or aggregated atypical cells consisting of large, pleomorphic nuclei with irregular membranes, chromatin clumps and prominent nucleoli. The morphology of the surgical specimen was similar to that of an anaplastic carcinoma and although it showed signs of transition from a normal follicular epithelium, there was no invasive growth or mitosis. This lesion was diagnosed as an atypical adenoma, and a papillary carcinoma was also present in the right lobe of the thyroid. Here we evaluate the molecular features of atypical adenomas in comparison with 9 ATC samples, and discuss whether or not atypical adenomas represent a form of premalignant lesion. Ki‐67 expression was found to be very low in atypical adenomas whereas all ATC samples showed high levels of Ki‐67 expression. Epithelial–mesenchymal transition (EMT) marker expression suggested that atypical adenomas maintain their epithelial phenotype to a higher degree than do ATCs. Differential diagnosis between ATC and atypical adenoma is difficult by cytological and histological methods alone, and Ki‐67 and EMT marker expression may support the diagnosis.     

Bilateral primary lymphoma of the breast: a case report initially diagnosed by FNAC

Primary lymphoma of the breast (PLB) is a rare disease, representing 0.04-0.5% of all malignant breast neoplasms. We present a patient with bilateral breast involvement by a high-grade diffuse large B-cell lymphoma, which was diagnosed initially by fine-needle aspiration cytology (FNAC). Mammography revealed a diffuse increase in density of the right breast and a large solitary mass on the left breast, suggestive of an inflammatory carcinoma. The patient underwent FNAC and the diagnosis of a non-Hodgkin's lymphoma (NHL) was suggested. Physical examination revealed palpable bilateral axillary lymph nodes but no evidence of concurrent widespread disease. The patient underwent complete staging evaluation. The only positive findings were an elevated lactate dehydrogenase (LDH) and evidence of axillary lymphadenopathy on CT. Excisional biopsy was performed on the left breast. The morphological and immunohistochemical analysis confirmed the diagnosis of a high-grade diffuse large B-cell lymphoma with an immunophenotype suggestive of a germinal center cell origin.     

Inflammatory pseudotumor of the liver in a patient with chronic hepatitis C: Difficulty in differentiating it from hepatocellular carcinoma

A case of an inflammatory pseudotumor of the liver in a 75-year-old female with chronic hepatitis C whose radiologic features simulated that of hepatocellular carcinoma (HCC) is presented. On imaging studies, hypervascularity by CO2 ultrasound (US) angiography, enhancement at an early phase and isodensity at a late phase by incremental dynamic computed tomography (CT), perfusion defect by CT during arteriography (CTAP), and clinical background of hepatitis C virus (HCV) infection strongly suggested HCC. A US-guided needle biopsy revealed a mainly diffuse and polyclonal proliferation of lymphocytes positive for leukocyte common antigen (pan-lymphocyte cells), L-26 (B cell lymphocytes), and UCHL-1 (T cell lymphocytes), negative for both kappa and lambda light chains and sparsely distributed neutrophils and histiocytes. No lymphoid follicles were observed. The liver tissue around this tumor showed chronic hepatitis with mild activity and mild fibrosis. These histopathologic findings suggested that the diagnosis of inflammatory pseudotumor of the liver was tenable. As it is difficult to differentiate between inflammatory pseudotumor of the liver and HCC by imaging studies alone, supplemental biopsy, where possible, should be obtained when diagnostic imaging of tumors suggesting HCC is carried out. We emphasize that histopathology is a true gold standard in the diagnosis of this disease.     

Metastatic extraocular sebaceous carcinoma with an occult primary

The cytological diagnosis of sebaceous carcinoma is based on the aspiration of tumor lobules with extensive sebaceous differentiation. However, these tumors may show a spectrum of cells ranging from basaloid to well-differentiated sebaceous. Extraocular sebaceous carcinoma is an uncommon tumor. An occult primary at initial presentation has not been described previously. A 60-yr old woman was referred to the fine-needle aspiration (FNA) clinic with a submandibular mass. The cytological diagnosis was mucoepidermoid carcinoma. Histopathologically, it was a sebaceous carcinoma metastatic to the submandibular lymph node. No primary tumor was identified. Six months later, she presented with a nodule at the angle of her mouth and a recurrence of the submandibular swelling. FNA cytology (FNAC) and histopathologic examination revealed a primary cutaneous sebaceous carcinoma with submandibular lymph node metastasis. A metastatic sebaceous carcinoma in the submandibular region with limited sebaceous differentiation and occult primary is another pitfall in the cytomorphological diagnosis of mucoepidermoid carcinoma.     

Malignant Adrenal Rest Tumor of the Retroperitoneum Producing Adrenocortical Steroids

We present a case of a malignant adrenal rest tumor arising from the retroperitoneum with Cushing's syndrome in a 31-year-old female. Her serum cortisol and dehydroepiandrosterone sulfate levels were elevated, while adrenocorticotropic hormone levels were low. Computed tomography scans and magnetic resonance imaging revealed a retroperitoneal tumor with no visible lesions in the adrenal glands and ovaries. From those results and the histopathologic findings following biopsy of an enlarged supraclavicular lymph node, the patient was diagnosed as a malignant adrenal rest tumor of the retroperitoneum. Despite chemotherapy, the patient died of rapid development of multiple metastases. Autopsy revealed a large tumor that extended around the abdominal aorta from the levels of the left kidney to the aortic bifurcation with generalized metastases. Tumor cells were characterized by clear and eosinophilic cytoplasm and atypical nuclei that exhibited frequent and atypical mitoses. Immunohistochemistry regarding steroidogenesis was performed and revealed that the tumor cells were immunopositive for adrenal 4 binding protein/steroidogenic factor-1, cholesterol side-chain cleavage enzyme, 17α-hydroxylase, and 21-hydroxylase. We thus elucidated the adrenocortical steroid production in the tumor cells causing Cushing's syndrome. This case report first demonstrates the steroidogenic capacity in a malignant adrenal rest tumor.     

Symptomatic Intraspinal Oncocytic Adrenocortical Adenoma

Most intraspinal neoplasms of epithelial origin are metastases from primary carcinomas. Benign epithelial tumors are rarely found at this site. We here present the case of a 44-year-old woman with a lesion in the cauda equina that fulfilled the radiologic criteria of schwannoma and caused clinical symptoms for 3 years. The excised tumor was composed of nests of large polygonal cells with eosinophilic partial granular cytoplasm. Significant atypia, necrosis, and mitosis were absent from this lesion. The tumor showed diffuse positivity for melan-A, synaptophysin, and alpha-inhibin. Steroidogenic factor 1 and cytokeratins 8 and 18 were focally seen in the absence of S-100 and chromogranin. This immunoprofile indicated adrenocortical origin. Ultrastructural examination showed abundant mitochondria, suggesting an oncocytic tumor. The diagnosis of an oncocytic adrenal cortical adenoma was made. These extraadrenal tumors are thought to arise from heterotopic adrenocortical tissue in the spinal cavity. Oncocytic tumors are rare neoplasms and they comprise non-functioning variants of adrenal cortical adenomas. To date, only five such intraspinal tumors have been observed. Immunohistochemistry excluded oncocytic paraganglioma, oncocytic meningioma, renal cell carcinoma, alveolar soft part sarcoma, and granular cell tumor. A view of the literature of these rare but probably underdiagnosed intraspinal tumors is given.     

Adenoid cystic carcinoma of maxillary sinus with metastatic hepatocellular carcinoma. Case report

A case of collision tumor in the left maxillary sinus composed of adenoid cystic carcinoma (ACC) and metastatic hepatocellular carcinoma (HCC) is reported. Radiographic examination revealed masses in the liver and bilateral lung metastases. Histologically, proliferation of tumor cells with resemblance to HCC was observed, in addition to the ACC. For this reason, differential diagnosis between a second primary tumor and metastasis was made. The metastatic lesion immunohistochemically showed positivity for hepatocyte antigen (OCH1E5) and protein induced by vitamin K absence or antagonist II (PIVKA-II), sustaining the HCC diagnosis. Primary ACC and metastatic HCC in the maxillary sinus are rare, and this may therefore be the first case of maxillary sinus tumor with both these elements.