Combined hepatocellular-cholangiocarcinoma and its mimickers: Diagnostic pitfalls in surgical pathology.

BACKGROUND: The diagnosis of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) requires histomorphological detection of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). However, these primary liver cancers (PLCs) have a wide variety of microscopic appearances resulting in difficulties and uncertainties in cHCC-CCA's diagnosis. This study aims to perform a clinicopathologic analysis on the diagnosis of PLCs at a tertiary referral hospital in Thailand using traditional morphologic studies. METHODS: A 5-year retrospective analysis of pathologically diagnosed PLCs was conducted. Pathological features and clinical characteristics of cHCC-CCA and other PLCs with the histopathologic resemblance to cHCC-CCA were studied. The pathological diagnosis was rendered based on histomorphological context rather than immunoreactivity. A literature review containing diagnostic pitfalls of cHCC-CCA was carried out. RESULTS: PLCs from a total of 295 patients were retrieved, and cHCC-CCA accounted for 1.4% (n = 4) of the malignancies. Histomorphological evaluation is the most reliable diagnostic modality for cHCC-CCA. Extremely uncommon variants of iCCA (i.e., mucinous iCCA and adenosquamous iCCA) and iCCA arising with hepatocellular nodular lesions (i.e., iCCA with nodular regenerative hyperplasia (NRH), and iCCA in cirrhosis) could have a histomorphologic resemblance to that of cHCC-CCA. CONCLUSIONS: Although there has been an exceedingly high incidence of iCCA in Thailand, such a commonness is not valid for cHCC-CCA in our series. Rare forms of iCCA could have a morphologic resemblance to that of cHCC-CCA. Regardless of the differentiation and immunophenotype, iCCA without a distinct HCC component should never be diagnosed as cHCC-CCA.

PET/MRI and genetic intrapatient heterogeneity in head and neck cancers.

PURPOSE: The relation between functional imaging and intrapatient genetic heterogeneity remains poorly understood. The aim of our study was to investigate spatial sampling and functional imaging by FDG-PET/MRI to describe intrapatient tumour heterogeneity. METHODS: Six patients with oropharyngeal cancer were included in this pilot study. Two tumour samples per patient were taken and sequenced by next-generation sequencing covering 327 genes relevant in head and neck cancer. Corresponding regions were delineated on pretherapeutic FDG-PET/MRI images to extract apparent diffusion coefficients and standardized uptake values. RESULTS: Samples were collected within the primary tumour (n = 3), within the primary tumour and the involved lymph node (n = 2) as well as within two independent primary tumours (n = 1). Genetic heterogeneity of the primary tumours was limited and most driver gene mutations were found ubiquitously. Slightly increasing heterogeneity was found between primary tumours and lymph node metastases. One private predicted driver mutation within a primary tumour and one in a lymph node were found. However, the two independent primary tumours did not show any shared mutations in spite of a clinically suspected field cancerosis. No conclusive correlation between genetic heterogeneity and heterogeneity of PET/MRI-derived parameters was observed. CONCLUSION: Our limited data suggest that single sampling might be sufficient in some patients with oropharyngeal cancer. However, few driver mutations might be missed and, if feasible, spatial sampling should be considered. In two independent primary tumours, both lesions should be sequenced. Our data with a limited number of patients do not support the concept that multiparametric PET/MRI features are useful to guide biopsies for genetic tumour characterization.

Renal cell carcinoma metastatic to a pituitary FSH/LH adenoma: case report and review of the literature.

Abstract Metastases to the pituitary occur more frequently in patients with widespread cancer and mainly involve the posterior lobe. A few cases of metastatic carcinoma to a pituitary adenoma have been described so far. Here, the authors present an additional case of a clear cell renal cell carcinoma (CCRCC) metastatic to a FSH/LH/α-subunit pituitary adenoma and systematically review the literature. Immunohistochemistry and electron microscopy were performed to characterize both neoplastic components at the morphological level. Moreover, it was hypothesized that expression of VEGF and of the corresponding receptor VEGFR1 could be implicated in the development of the carcinomatous metastasis within the adenoma.

[Mucocele of the appendix - a heterogenous surgical pathology]. / Die Mukozele der Appendix - eine inhomogene chirurgische Krankheitsentität.

BACKGROUND: Mucoceles of the appendix are rare. After appendectomy, mucoceles are detected with a frequency of 0.2 to 0.3 %. Both stenosing / obliterating processes and alterations of the epithelium (hyperplasia, mucinous cystadenoma, cystadenoma with uncertain malignant potential (UMP), mucinous cystadenocarcinoma lead to the occurrence of mucoceles. The perforation of a mucocele with possible spread of mucus and cells into the abdominal cavity constitutes a severe complication (pseudomyxoma peritonei). Surgical resection is the curative approach for mucoceles of the appendix. MATERIALS AND METHODS: Data of patients who were treated for an appendiceal mucocele between 1995 and 2009 were analysed retrospectively with regard to clinical presentation, diagnostic measures, surgical procedure and histopathological result. Follow-up was evaluated in telephone interviews. RESULTS: We extracted 5 cases from our database. Clinical symptoms varied greatly among the individual patients, ranging from peracute abdominal pain in the right lower quadrant to chronic obstipation. Results from abdominal ultrasound and / or abdominal CT scans contributed to the indication for surgical intervention in all cases. In 2 patients surgery was stated as urgent whereas in 3 the operation was scheduled electively. In one patient the diagnosis of an appendiceal mucocele was stated preoperatively and in another intraoperatively. In 3 patients only the histopathological result revealed the underlying mucocele. We performed 1 open and 1 laparoscopic appendectomy, 1 open appendectomy with a partial resection of the coecum and 2 laparoscopic ileocoecal resections. One of the patients had a pseudomyxoma peritonei. The histopathological diagnoses ranged from mere epithelial hyperplasia to an adenoma with uncertain malignant potential and a mucinous cystadenocarcinoma. One patient's long-term follow-up could not be evaluated. All other patients had neither recurrence nor any complications after discharge. CONCLUSIONS: Mucoceles of the appendix present with a wide spectrum of clinical symptoms and histopathological alterations. Only an accurate histological analysis reveals the underlying pathological lesion correctly. This study emphasises that a mucocele of the appendix constitutes an important differential diagnosis in patients presenting with pathologies in their right lower abdominal quadrant.

Chorangiocarcinoma: a case report and review of the literature.

Chorangiocarcinoma is the name designated to a chorangioma with trophoblastic proliferation manifesting increased proliferative activity. Only 3 such cases have been published so far. Other studies challenged this entity by demonstrating that proliferation of the trophoblast around chorangioma is a common phenomenon. We present a case of a unique vascular lesion in a term placenta with a malignant trophoblastic component. Microscopic examination of a well-demarcated placental mass revealed a chorangioma with multiple nodules composed of pleomorphic cells displaying focal multinucleation, large areas of necrosis, and high mitotic activity. Immunohistochemical stains of these cells were strongly positive for pancytokeratin and the beta subunit of human chorionic gonadotropin and focally positive for HSD3B1. There was no invasion of the basement membrane, and no free-floating tumor cells in the intervillous space. No evidence of metastasis was found on follow-up of the mother and newborn. It is concluded that the tumor presented herein, displaying a histologically unequivocal malignant trophoblastic component in a benign chorangioma, is a true chorangiocarcinoma, and should be included within the category of gestational neoplasia as a tumor closely related to choriocarcinoma.

Subependymal giant cell astrocytoma (SEGA): Is it an astrocytoma? Morphological, immunohistochemical and ultrastructural study.

Subependymal giant-cell astrocytoma (SEGA) is a rare intra-ventricular low-grade tumor which frequently occurs as a manifestation of tuberous sclerosis complex. The histogenesis of SEGA is controversial and its astrocytic nature has been doubted. First studies suggested the astrocytic nature of SEGA while several recent reports demonstrate its glio-neuronal nature. In spite of this, in the recently revised WHO classification of the CNS tumors, SEGA has been still included in the group of astrocytomas. We studied nine tuberous sclerosis complex-associated SEGAs. Patients were 1-18 years old. Eight patients (89%) had a solitary lesion located in the lateral ventricle close to of the head of the caudate nucleus, the remaining patient (11%) had two tumors, one located close to the head of the left caudate nucleus and the other in the central part of the right lateral ventricle. Histologically, tumors were composed of three types of cells: spindle, gemistocytic and ganglion-like. Four tumors (44%) had a prominent vascularization and three (33%) showed an angiocentric pattern. Calcifications were observed in six cases (66%). By immunohistochemistry, the majority of the tumors were GFAP- (9; 100%), neurofilament- (8, 89%), neuron-specific enolase- (9, 100%), and synaptophysin- (8; 89%) positive. Ultrastructural studies were performed on four cases. In all four there were glial cell processes filled with intermediate filaments. In one case dense core putative neurosecretory granules were appreciable. Our results emphasize the glio-neuronal nature of SEGA. We suggest moving it into the group of mixed glio-neuronal tumors under the denomination of subependymal giant cell tumor.

Effect of primary site on prognosis in patients with cutaneous malignant melanoma. A study using a new model to analyse anatomical locations.

The prognostic impact of different anatomical sites in patients with cutaneous malignant melanoma (CMM) has been widely debated and requires further elucidation. Therefore, we developed EssDoll, a new computerized method to address the question of site in relation to prognosis. A population-based cohort of 1891 patients, diagnosed between 1976 and 1987 with invasive CMM without evidence of metastasis, was identified. The body surface was divided into 24 areas. Hazard ratios (HRs) for CMM death were calculated and areas were compared in both the whole model and in pairs. Cox's proportional hazard regression model was used and adjustments were made for established prognostic factors. Furthermore, the overall effect of site was calculated using the likelihood ratio test. Overall, the tumour site was of prognostic importance (P=0.0036). There was a significantly increased risk of CMM-specific death in patients with a primary tumour site in the middle and lower back (HR=1.8, P=0.04) and in the supramammary and mammary area (HR=1.8, P=0.05). When all areas were analysed in pairs, the dorsal shoulder, superior back and clavicular area also showed a worse prognosis. CMM diagnosed in other anatomical regions, including the calves, Achilles, upper arms, forehead, temples, cheeks and face, seemed to be related to a better prognosis. It can be concluded that the tumour site is of prognostic importance, and that the middle and lower back and supramammary and mammary areas are independent factors related to a poor prognosis.

Multiple trichoepitheliomas in an alpaca (Lama pacos).

A 13-yr-old male Alpaca (Lama pacos) presented with multiple ovoid, well-circumscribed, nonulcerated intradermal masses. Individual masses measured 1-4 cm in diameter, and the overlying skin was alopecic. Several of the masses were surgically removed and evaluated microscopically. Histopathologic evaluation demonstrated multiple dermal cysts lined by neoplastic follicular epithelium. The cysts were filled with multiple layers of lamellar keratin and lined by abortive inner and outer root sheaths exhibiting cellular atypia, supporting the diagnosis of trichoepitheliomas. No additional treatment was initiated, and the alpaca continues to do well.

Adrenal cortical adenoma with excess black pigment deposition, combined with myelolipoma and clinical Cushing's syndrome.

We report a case of a functional adenoma with excess black pigment deposition and myelolipoma in the same adrenal gland in a 58-year-old woman. The patient presented with gastrointestinal bleeding, and after being diagnosed with colonic diverticulosis, underwent a total colectomy. An abdominal computerized tomographic (CT) scan during her work-up showed a right adrenal mass consistent with myelolipoma. Postoperatively, the patient was diagnosed with Cushing's syndrome and underwent a right adrenalectomy. The adrenalectomy specimen consisted of a dark brown and golden-yellow adrenal adenoma, myelolipoma, and atrophic adrenal gland. Immunostains indicated that the dark brown adenoma component was responsible for the patient's hypercortisolism. Co-occurrence of a functional black adenoma and a well-developed myelolipoma has not been reported in the literature. We describe the significant findings of this case, together with a review of the literature.

Sclerosing hemangioma of the lung in a young woman with cutaneous melanoma: the role of electron microscopy in preventing an erroneous diagnosis of metastasis.

A young woman with a melanoma of the left forearm was found to have a right lung mass. This was initially interpreted as metastatic melanoma on the basis of clinical, radiographic, and light microscopic features, together with positive staining of tumor cells with antibody HMB-45. Electron microscopic examination performed for confirmation of the diagnosis revealed no evidence of melanocytic differentiation. Instead, there were features suggestive of the alternative diagnosis of sclerosing hemangioma (SH). This diagnosis was confirmed with additional immunocytochemical stains. To the authors' knowledge this is the first report of HMB-45 positivity in SH. This case illustrates a potentially disastrous diagnostic pitfall in interpreting lung tumors in patients with melanoma, and the vital role of electron microscopy in resolving conflicting and/or misleading immunocytochemical results.

Non-invasive lobular carcinoma within a fibroadenoma, a preoperatively diagnosed case.

Breast cancer within a fibroadenoma is rare and usually diagnosed postoperatively from pathological specimens. This paper reports a 54-year-old female with non-invasive carcinoma within a fibroadenoma, diagnosed preoperatively. She underwent a medical examination and mastopathy was suspected. On physical examination a mass 2 cm in diameter was palpated in the left breast. Ultrasonography showed a mass with smooth margins and uniform internal echoes, but cytology showed malignancy. Mammography showed a round mass with distinct margins and no calcification. As fibroadenoma, diagnosed by ultrasonography and mammography, and breast cancer, diagnosed by cytology, were not consistent results several core biopsies were performed. Needle biopsy showed proliferation of atypical epithelial cells; breast cancer within a fibroadenoma was diagnosed. MRI showed a circular mass with distinct, smooth margins and in a dynamic study, the mass showed irregular staining and the presence of early staining. Left lumpectomy and dissection of the left axillary lymph nodes was performed. Histological examination showed non-invasive lobular carcinoma occurring within a fibroadenoma.

Acinar-islet cell tumor of the pancreas: report of a malignant pancreatic composite tumor.

An unusual case of malignant pancreatic composite tumor with both components of acinar cell tumor (ACT) and islet cell tumor (ICT) was investigated histologically, immunohistochemically, and ultrastructurally. The pancreatic tumor with central cyst formation was found on computerized tomographic examination of a 72-year-old man reporting appetite and weight loss. The ACT component was present in the original pancreatic region and the ICT region was adjacent to the ACT. ACT was immunohistochemically positive for pancreatic amylase, whereas ICT had argyrophil tumor cells immunohistochemically positive for chromogranin A. There were several tumor cell nests positive for both pancreatic amylase (acinar differentiation) and chromogranin A (islet differentiation). We speculated that ICT may have arisen from the de-differentiated tumor cells in the ACT after the occurrence of ACT.

Sinonasal teratocarcinosarcoma: ultrastructural and immunohistochemical evidence of neuroectodermal origin.

The authors report a case of sinonasal teratocarcinosarcoma in a 37-year-old man, which was located in the anterior skull base and extended to the right nasal cavity and paranasal sinuses. The tumor was surgically resected twice, but it could not be removed completely. Microscopically, it was mainly composed of primitive cell nests within a moderately cellular stroma. The components of squamous cell epithelia with focal teratoid appearance and adenocarcinomatous differentiation were observed. There were many rhabdomyoblasts scattered in the nests and stroma. Ultrastructurally, the primitive cells had many neural processes with parallel microtubules, resembling olfactory neuroblastoma. Rhabdomyoblasts showed various degrees of skeletal muscle differentiation. Some of the stromal spindle cells had actin filaments with dense patches and dense core granules. Immunohistochemically, the primitive cells were positive for epithelial markers, neuron-specific enolase, synaptophysin, and myogenic regulatory proteins. The rhabdomyoblasts showed immunoreactivity for myoid markers, cytokeratin, epithelial membrane antigen, and synaptophysin. Most of the stromal spindle cells were positive for smooth muscle actin, neuron-specific enolase and synaptophysin. The immunohistochemical and ultrastructural findings suggest that primitive cells had the most primitive phenotype of placodes, and support the possibility that sinonasal teratocarcinosarcoma is essentially a neuroectodermal tumor with divergent differentiation.

Malignant phyllodes tumor in the right breast and invasive lobular carcinoma within fibroadenoma in the other: case report.

CONTEXT: The malignant variety of the phyllodes tumor is rare. The occurrence of invasive lobular carcinoma within fibroadenoma is rare as well. DESIGN: Case report. CASE REPORT: A 58-year-old black female patient was referred to the Mastology unit of the Department of Gynecology, Federal University of São Paulo / Escola Paulista de Medicina, in February 1990, presenting an ulcerated tumor in the right breast with fast growth over the preceding six months. She was a virgin, with meno-pause at the age of 45 years and had not undergone hormone replacement treatment. The physical examination showed, in her right breast, an ulcerated tumor of 20 x 30 cm which was not adher-ent to the muscle level, multilobular and with fibroelastic consistency. The axillary lymph nodes were not palpable. The left breast showed a 2 x 3 cm painless, movable nodule, with well-defined edges, and fibroelastic consistency. We performed left-breast mammography, which showed several nodules with well-defined edges, the largest being 2 x 3 cm and exhibiting rough calcification and grouped microcalcifications within it. The patient underwent a frozen biopsy that showed a malignant variant of the phyllodes tumor in the right breast and fibroadenoma in the left one. After that, we performed a total mastectomy in the right breast and an excision biopsy in the left one. Paraffin study confirmed the frozen biopsy result from the right breast, yet we observed that in the interior of the fibroadenoma that was removed on the left, there was a focal area of invasive lobular carcinoma measuring 0.4 cm. The patient then underwent a modi-fied radical mastectomy with total axillary lymphadenectomy. None of the 21 dissected lymph nodes showed evidence of metastasis. In the follow-up, the patient evolved asymptomatically and with normal physical and laboratory examination results up to July 1997.

Collision of uterine rhabdoid tumor and endometrioid adenocarcinoma: a case report and review of the literature.

Extrarenal malignant rhabdoid tumors have been reported in a variety of anatomic sites but infrequently in the female genital tract. In the uterus, they have been described as a pure tumor, in association with endometrial stromal sarcomas, and as a component of a malignant mullerian mixed tumor. This study reports an unusual uterine neoplasm in a 49-year-old woman, in which a malignant rhabdoid tumor occurred as a collision tumor with a well-differentiated endometrioid adenocarcinoma. The tumor was a 14-cm polypoid mass that filled the endometrial cavity. The two neoplastic components were distinct on microscopic and immunohistochemical examination. Ultrastructural examination confirmed the rhabdoid phenotype of the sarcomatous component. The patient died of disease 4 months after diagnosis with progression of the malignant rhabdoid tumor. The highly aggressive behavior of the rhabdoid (i.e., nonepithelial) component in this collision tumor lends support for a distinction of this neoplasm from a malignant mullerian mixed tumor, with which it may be confused.

Initiation of ectopic epithelial calcification in a calcifying odontogenic cyst.

Ultrastructural observation was performed on a calcifying odontogenic cyst (COC) associated with an odontoma and arising in the right mandibular region of an 8-year-old Japanese boy. Four types of cells were identified in the epithelial layer of the COC. The basal cells were low columnar in shape and contained some intracellular organelles. They were attached to the neighboring cells with a few desmosomes and resembled inner enamel epithelium of the normal enamel organ. The stellate reticulum-like cells, polygonal in shape, possessed desmosomes and many cytoplasmic projections. Some intracellular organelles and a few bundles of tonofilaments were observed in the cytoplasm. The light oval cells that were pale staining with toluidine blue contained dilated membranous organelles and many relatively evenly distributed tonofilaments. These cells were usually scattered in the vicinity of the focal accumulations of ghost cells, and the cell membrane was discontinuous in parts. The ghost cells contained many bundles of tonofilaments that were 60-240 nm in diameter and arranged in various directions. No intact intracellular organelles were noted in the cytoplasm. They were attached to the neighboring ghost cells with some desmosomes and their cell membrane was discontinuous in parts. A variety of vesicles, 90-450 nm in diameter, were scattered among the tonofilament bundles. Some of these contained needle-like crystals that were considered to be initial calcification sites in ghost cells. These vesicles presented morphological similarities to matrix vesicles, and it is therefore suggested that matrix vesicle-like structures are deeply involved with initiation of calcification of ghost cells in COC.

Mucoepidermoid carcinoma arising in Warthin's tumour of the parotid gland: report of two cases with histopathological, ultrastructural and immunohistochemical studies.

AIMS: Malignant transformation of Warthin's tumour (WT) is a rare event. We present two cases of mucoepidermoid carcinoma (MEC) arising in WT in the parotid gland. METHODS AND RESULTS: Two cases of MEC arising in WT, which were found in 185 cases of WT of the parotid gland, were investigated by light and electron microscopy, and immunohistochemistry. Both cases had largely similar macroscopic and histological features with some differences. Histologically, the tumours consisted mainly of WT with multilayered hyperplastic arrangements of oncocytic cells and focal squamous and goblet cell metaplasia. In the same tumour mass, however, the features of MEC were observed with invasion to adjacent adipose tissue. A transitional zone between WT and MEC was evident. Both patients were alive and well without evidence of recurrence 30 and 34 months after surgery, respectively. Electron microscopy revealed that cyst lining epithelial cells in WTs had abundant mitochondria whereas some of the MEC cells contained numerous tonofilaments and mucinous granules. Immunohistochemically, oncocytic cells of WTs were strongly positive for mitochondria and SalylTn was extensively stained in MECs. The labelling index for Ki67 was obviously higher in the carcinoma cells than the epithelial cells of WT. CONCLUSIONS: Our cases confirmed the possibility of malignant transformation of the epithelial component in WT to MEC.