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Non-neoplastic granulosa cells within ovarian vascular channels: a rare potential diagnostic pitfall.

AIMS: To describe six cases seen in consultation in which artefactual vascular involvement within the ovary by benign granulosa cells caused diagnostic confusion. METHODS/RESULTS: In five cases, the initial favoured diagnoses of the submitting pathologists were metastatic carcinoma (three cases) and immature neural elements within a teratoma (two cases). In two cases, the ovary contained a benign cystic teratoma (one with struma ovarii), in two cases endometriosis, in one case follicular cysts, and in the other no pathological lesion was present. In all cases, several small ovarian vascular channels contained cohesive groups of cells with mildly atypical nuclei and cytoplasm, which varied from scant to abundant and eosinophilic. In four cases, mitotic figures were identified. The cells were morphologically consistent with benign granulosa cells and were associated in four cases with a nearby follicle lined by similar cells. There was no evidence of a mass lesion, grossly or histologically, to suggest a granulosa cell tumour. The nature of the cells was confirmed using immunohistochemistry for alpha inhibin and calretinin in one case. CONCLUSIONS: This phenomenon is probably an artefact secondary to surgical trauma or sectioning within the laboratory; alternatively, it could be related to ovulation. It is important that this benign process is not misinterpreted as cancer, either primary or metastatic, which may prompt inappropriate treatment or investigations that are not needed.

Adult↗

Basement membrane material (hyaline globules) in synovial sarcoma. A case report with description of a potential diagnostic pitfall.

BACKGROUND: Synovial sarcoma (SS), a malignant mesenchymal tumor, has a biphasic growth pattern characteristically. Histologically and cytologically the tumor can pose diagnostic difficulty when the epithelial component is predominant. CASE REPORT: A 22-year-old female presented with a rapidly enlarging mass on the lower left side of the neck. Fine needle aspiration of the tumor yielded abundant, discohesive round-oval cells mingled with amorphous hyaline material, raising a suspicion of medullary carcinoma of the thyroid. In addition, air-dried, Giemsa-stained smears demonstrated rosettelike structures with central magenta globular material, mimicking adenoid cystic carcinoma. However, histologic examination of the excised tumor, including immunohistochemical and ultrastructural studies, proved it to be a typical SS with copious basement membrane accumulations. CONCLUSION: The cytologic appearance of SS can be confusing. However, a false diagnosis may be avoided if adequate needle sampling is ensured and clinical correlation considered.

Adult↗

Fine-needle aspiration of pancreatic serous cystadenoma: cytologic features and diagnostic pitfalls.

BACKGROUND: The preoperative diagnosis of pancreatic serous cystadenoma (SCA) is important because as a typically benign tumor it can be treated expectantly, whereas many other cystic tumors require excision. This study examines the cytology, clinical and radiologic features, diagnostic accuracy of fine-needle aspiration (FNA), and potential pitfalls associated with this rare tumor. METHODS: Cytomorphologic features were retrospectively reviewed from 28 FNAs of SCA from 21 patients. FNA biopsies were guided by percutaneous computed tomographic or ultrasonographic imaging in 10 cases and by endoscopic ultrasonographic imaging in 18 cases. Corresponding histology (14 tumors) and clinical/imaging findings were also evaluated. RESULTS: Patients typically presented with upper abdominal discomfort or asymptomatically. Radiologically, a well-demarcated, multiloculated cystic mass involving the pancreatic head or uncinate process was common. Aspirates were sparsely cellular against a clean or granular, proteinaceous background. Tumor cells formed loose clusters or monolayered sheets composed of cuboidal cells with indistinct cell borders and granular or clear cytoplasm that was often stripped from the nucleus. Nuclei were small, round, with fine chromatin and indistinct nucleoli and devoid of mitotic activity. Seven (25%) of the aspirates were initially classified as "consistent with SCA," 6 (21%) as "no malignant cells," 3 (11%) as "nondiagnostic specimen," 3 (11%) as "suspicious for malignancy," 3 (11%) as "rare atypical cells," and 6 (21%) as "probably or consistent with mucinous cystic neoplasm." Features causing diagnostic difficulty were scant cellularity, papillary groups, nuclear atypia, and columnar cells mimicking those of mucinous neoplasms. Gastrointestinal (GI) epithelium and mucin also caused confusion. The detection of intracytoplasmic glycogen (3 of 6 cases) and cyst fluid analysis (2 of 2 cases) showing low viscosity and low or undetectable levels of carcinoembryonic antigen, CA 19.9, and amylase enhanced diagnostic confidence. CONCLUSIONS: Diagnosing SCA by FNA is challenging. Familiarity with its morphologic spectrum, use of ancillary studies, and correlation with clinical/radiologic findings greatly improves diagnostic accuracy. Contaminating GI epithelium and mucin should be distinguished from components of a mucinous neoplasm.

Adult↗

Malignant melanoma with a myxoid stroma: a diagnostic pitfall on fine-needle aspiration biopsy.

Malignant melanoma (MM), both primary and metastatic, may be associated with a prominent myxoid stromal reaction causing diagnostic confusion on fine-needle aspiration biopsy (FNAB), most often with sarcomas that demonstrate a myxoid stroma, particularly malignant peripheral nerve sheath tumor (MPNST). We present a case of a 32-yr-old man with no past medical history who presented with a unilateral neck mass clinically suspicious for lymphoma. FNAB produced a specimen composed of large sheets of anaplastic cells encased in a myxoid stroma that was S100 and vimentin-positive but HMB-45-negative. A diagnosis of MPNST was made. Excision demonstrated a metastatic MM of unknown primary, with a prominent myxoid stromal reaction. A repeat HMB-45 was again negative. Electron microscopy demonstrated intracytoplasmic melanasomes and cisternae of rough endoplasmic reticulum with intracisternal parallel tubules, confirming the diagnosis. Although HMB-45 is typically negative in both tumors, S100 should be strongly positive in myxoid MM and only focal in MPNST.

Adult↗

Diagnostic pitfalls of fine needle aspiration cytology for breast disease.

We analysed 1500 consecutive fine needle aspiration cytology (FNAC) specimens to ascertain the reasons for diagnostic failure. Of 221 tumours proven malignant following open biopsy, 184 (83%) were correctly diagnosed on FNAC. Of 1082 aspirates classified 'benign', 787 (73%) underwent open biopsy and of these 33 (4%) were diagnosed malignant. All three cases of ductal carcinoma in-situ (DCIS) and eight of 16 lobular carcinomas in this study were missed using FNAC alone. Twelve of the 22 patients with invasive carcinoma not diagnosed on cytology had tumours measuring less than 1 cm diameter. Six of 1500 FNAC reports (0.4%) gave false positive diagnoses, five were classified as 'suspicious of malignancy; and one as 'frankly malignant'. The overall sensitivity was 84%, specificity 99% and positive predictive value 97%. Though these results confirm the value of FNAC as a rapid means of diagnosing most breast cancers, it it unreliable in patients with invasive carcinomas less than 1 cm in diameter and for the detection of lobular and in-situ carcinoma.

Biopsy, Needle↗

Bilateral tubal ectopic pregnancy: diagnostic pitfalls.

A rare case of simultaneous bilateral tubal pregnancy after natural conception is presented, together with a review of the literature on this topic. Diagnostic aspects and treatment options are discussed.

Adult↗

Fine needle aspiration cytology of subareolar abscess of the breast. Spectrum of cytomorphologic findings and potential diagnostic pitfalls.

The cytomorphologic findings of eight cases of subareolar abscess of the breast diagnosed by fine needle aspiration (FNA) biopsy are presented. A spectrum of cytologic findings was appreciated, including diagnostic anucleated squames associated with numerous neutrophils, keratinous debris, cholesterol crystals, parakeratosis and strips of squamous epithelium. A foreign-body reaction, with sheets of histiocytes and multinucleated foreign-body-type giant cells, was noted in some of the cases. Potential pitfalls for a false-positive diagnosis of malignancy included the presence of groups of atypical ductal cells, squamous atypia and fragments of exuberant granulation tissue. Seven of the eight cases had complete surgical excision of the lesion, which demonstrated the characteristic findings of dilated lactiferous ducts undergoing squamous metaplasia with rupture and surrounding extensive acute and chronic inflammation with foreign-body reaction. With recognition of the FNA cytologic findings of subareolar abscess of the breast, a specific diagnosis can be rendered, which then allows different treatment modalities depending on the stage of the lesion. Appreciation of the spectrum of cytologic features will enable the pathologist to make the correct diagnosis and thereby avoid potential pitfalls that can possibly lead to a false-positive diagnosis of malignancy.

Abscess↗

Soft tissue Rosai Dorfman disease mimicking inflammatory pseudotumor: a diagnostic pitfall.

Rosai Dorfman disease, or sinus histiocytosis with massive lymphadenopathy (SHML), may be a difficult diagnosis to make, especially in extranodal sites. With soft tissue involvement the characteristic diagnostic features of large histiocytic cells with emperipolesis may be overshadowed by a fibroinflammatory component. In these cases it is easy to confuse this lesion with reactive nodules and benign and malignant neoplasms. We report a case in which soft tissue SHML was confused with an inflammatory pseudotumor. Only after review, when other extranodal sites became apparent, was the correct diagnosis made. Pitfalls in the diagnosis of soft tissue SHML are discussed.

Biopsy↗

Preoperative and intraoperative diagnosis of low-grade adenosquamous carcinoma of the breast: potential diagnostic pitfalls.

AIMS: Low-grade adenosquamous carcinoma (LGAC), a rare variant of metaplastic breast cancer, may mimic benign or other low-grade malignant lesions histologically. Diagnostic difficulty may be encountered when evaluating breast cytology, core needle biopsy or intraoperative frozen section specimens. METHODS AND RESULTS: Pathology reports, cytology aspirates and histological slides of LGAC diagnosed at the Department of Pathology, Singapore General Hospital, were reviewed. Four cases of LGAC were analysed. Cytology from the first case showed atypical cells and the subsequent surgical excision specimen showed a complex sclerosing lesion with LGAC. The second and third cases were investigated by core needle biopsies: the preoperative histological features were suggestive of but not diagnostic of LGAC, until further excision biopsies were performed. The fourth case entailed a frozen section specimen, for which definitive diagnosis was deferred to paraffins. The patients remained well with no evidence of recurrent disease to date. CONCLUSIONS: When limited material, in the form of needle aspirates, core biopsy specimens or frozen sections, is submitted for histology, making a diagnosis of LGAC is not only challenging, but may be impossible. In difficult cases, careful pathological assessment, clinicopathological correlation and follow-up or complete excision biopsy may prove invaluable in establishing a definitive diagnosis.

Biomarkers, Tumor↗

Multinucleate giant cells in sublabial salivary gland tissue in Sjögren's syndrome. A diagnostic pitfall.

The presence of multinucleate giant cells in the sublabial salivary gland tissue in Sjögren's syndrome is an unusual phenomenon which can give rise to differential diagnostic problems. We found in 4 cases of 55 patients with Sjögren's syndrome multinucleate giant cells. In 2 of these 4 patients epimyoepithelial islands were also present. The combination of both multinucleate giant cells as epimyoepithelial islands can mimic the histological picture of a non- caseating granulomatous disease. To discriminate between an epimyoepithelial island and an epithelioid granuloma the immunoperoxidase technique with antibodies directed against muramidase appeared an useful tool. The epithelioid cells contain muramidase whereas the cells in the epimyoepithelial island do not contain this enzyme. Thus, multinucleate giant cells are a rare phenomenon in Sjögren's syndrome, therefore restricting its diagnostic significance. When they occur in Sjögren's syndrome staining for muramidase can be of help to avoid a false positive diagnosis of diseases in which non- caseating granulomatous inflammation occur, such as in sarcoidosis.

Adult↗

Diagnostic pitfalls and therapeutic strategies in the treatment of pancreatic duct haemorrhage.

Haemorrhage via the pancreatic duct, a rare cause of upper gastrointestinal bleeding (GIB), often poses a diagnostic dilemma. We analysed our experience with 10 patients (8 men, 2 women; mean age 44 years, range 34-62) treated during a 12 year period. All had a history of alcohol abuse and presented with major upper GIB requiring a median of 8 units (range 2-40) blood transfusion. Nine had upper abdominal pain at the time of admission and nine had a history of pancreatitis. Upper gastroduodenal endoscopy (median 4; range 1-9), was diagnostic in only one. Side-viewing endoscopy showed bleeding from the pancreatic duct in 7 of 8 patients. Visceral aneurysms were demonstrated in 7 of 9 patients in whom coeliac angiography was carried out: (splenic artery 4, gastroduodenal artery 2, and pancreaticoduodenal artery 1). Two of 4 selective embolisations were successful. Six patients underwent distal pancreatectomy, 1 had gastroduodenal artery ligation and 1 died of coagulopathy following a total pancreatectomy. Pancreatic duct haemorrhage should be considered in patients with unexplained recurrent upper GIB, alcohol abuse and epigastric pain, particularly in those with established chronic pancreatitis. Selective angiography is essential for diagnosis and management. For bleeding sites in the head of the pancreas, embolisation should be attempted to avoid major resection. Distal pancreatectomy is preferred for splenic artery lesions.

Adult↗

Diagnostic pitfalls in abdominal CT.

Many factors result in suboptimal performance of abdominal computed tomography (CT) or inaccurate interpretation of the images. Improper technique, observers' errors, and lack of clinical information are major contributors to misdiagnoses. Because of inadequate oral administration of contrast material, normal structures (eg, bowel) may remain unopacified and simulate tumors. Repeat scanning with additional contrast material and sodium bicarbonate, at selected levels, and perhaps with changes in patient position often reveals the true nature of pseudotumors in the gastrointestinal tract. Dynamic CT of the liver, performed during contrast material injection, yields the best results. Occasionally, reconstruction of axial images in coronal or sagittal planes helps delineate normal sectional anatomic variations of the diaphragm and liver and avoid misdiagnosis of pseudomasses. Volume averaging can cause problems when the section thicknesses are larger than the lesions (eg, small hepatic cysts) or structures are very close (eg, kidney and spleen); repeat CT with thinner sections is needed to obtain accurate attenuation values or delineate normal anatomic relationships. The gallbladder, spleen, and pancreas can change position due to prior surgery and raise suspicion of a mass unless clinical history is known. Familiarity with these and other pitfalls described herein should lead to accurate interpretation of CT scans.

Diagnostic Errors↗

'Mucin-positive' epithelial mesothelioma of the peritoneum: an unusual diagnostic pitfall.

AIMS: The histopathological, immunohistochemical and ultrastructural features of a primary 'mucin-positive' epithelial mesothelioma of the peritoneum are reported to draw attention to a potential cause of diagnostic error. METHODS AND RESULTS: Light microscopy showed an infiltrative neoplasm within the gastric wall and omentum which was composed of sheets of 'signet- ring' tumour cells and contained abundant diastase-resistant periodic acid-Schiff-positive material. Immunohistochemistry supported a mesothelial phenotype (cytokeratin AE1/3, thick membranous HBME-1, focal thrombomodulin and calretinin expression and no reactivity for carcinoembryonic antigen, Leu-M1 and Ber-EP4). Ultrastructural features showed large cells with prominent intercellular desmosomes and numerous delicate, elongated microvilli. Within intracytoplasmic neolumina, crystalloidal 'fern-like' bodies were identified with features similar to the ultrastructural appearances of hyaluronic acid crystals. Repeat histochemical analysis following hyaluronidase pretreatment revealed a significantly diminished diastase-resistant periodic acid-Schiff reaction. CONCLUSIONS: This case of primary peritoneal 'mucin-positive' epithelial mesothelioma demonstrates morphological and histochemical mimicry with diffuse gastric adenocarcinoma. A similar case has not been previously reported in the peritoneum and an awareness of the tumour (with application of suitable ancillary studies) prevents misdiagnosis and assists in potentially difficult medicolegal cases.

Adenocarcinoma↗