Solid Cell Nests Research Articles

BRAF mutation in solid cell nest hyperplasia associated with papillary thyroid carcinoma. A precursor lesion?

We describe a case of solid cell nest hyperplasia associated with papillary thyroid carcinoma in a 48-year-old man with goiter. The entire gland was examined; in 1 section, the cells of 1 solid cell nest were in close contact with a follicular variant of papillary microcarcinoma. A second follicular variant of papillary microcarcinoma, 1 follicular adenoma, hyperplastic nodules, and some lymphoid aggregates were also found. Scattered p63-positive cells were found in the second papillary microcarcinoma. After microdissection, the same BRAF(V600E) mutation was found both in a pool of 5 solid cell nests and in the adjacent papillary microcarcinoma. BRAF(V600E) mutation and the previously unreported BRAF(G593D) mutation along with p.G606G silent change were found in the second papillary microcarcinoma, but no mutations were detected in the follicular adenoma or in the 2 other pools of solid cell nests screened for BRAF gene mutations. These findings support a histogenetic link between the main cells of solid cell nests and papillary thyroid carcinoma, and suggest solid cell nest hyperplasia as a precursor lesion of papillary thyroid carcinoma.

Mucoepidermoid carcinoma of the thyroid gland showing marked ciliation suggestive of its pathogenesis

Mucoepidermoid carcinoma of the thyroid gland is a rare tumor first described by Rhatigan et al. in 1977. Its pathogenesis is still controversial. With regard to its most likely origin, some authors have suggested that it arises directly from follicular epithelium whereas others have proposed that it arises from ultimobranchial body (diverticulum from the fourth pharyngeal pouch) remnants, also known as solid cell nests (SCN). Herein is reported a unique case of thyroid mucoepidermoid carcinoma. The patient, a 67-year-old man, presented with a non-tender thyroid mass and vocal cord fixation. The tumor was poorly defined, necessitating subtotal thyroidectomy with composite resection of the adjacent structures. Pathologically, the tumor cells had characteristics of mucoepidermoid carcinoma, along with layers of columnar cells showing marked ciliation resembling respiratory-type epithelium, suggesting that this rare tumor had originated from SCN. p63 immunopositivity in the tumor provided additional evidence for the pathogenesis.

A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a well recognized complication of advanced NASH (non-alcoholic steatohepatitis). We sought to produce a rat model of NASH, cirrhosis and HCC. Adult Sprague-Dawley rats, weighing 250-300g, were fed a choline-deficient, high trans-fat diet and exposed to DEN in drinking water. After 16 weeks, the animals underwent liver ultrasound (US), sacrifice and assessment by microscopy, immunohistochemistry and transmission electron microscopy (TEM). US revealed steatosis and focal lesions in 6 of 7. All had steatohepatitis defined as inflammation, advanced fibrosis and ballooning with Mallory-Denk bodies (MDB) with frank cirrhosis in 6. Areas of more severe injury were associated with anti-CK19 positive ductular reaction. HCC, present in all, were macro-trabecullar or solid with polyhedral cells with foci of steatosis and ballooned cells. CK19 was positive in single or solid nests of oval cells and in neoplastic hepatocytes. TEM showed ballooning with small droplet fat, dilated endoplasmic reticulum and MDB in non-neoplastic hepatocytes and small droplet steatosis in some cancer cells. This model replicated many features of NASH including steatohepatitis with ballooning, fibrosis, cirrhosis and hepatocellular carcinoma. Oval cell proliferation was evident and the presence anti-CK 19 positivity in the cancer suggests oval cell origin of the malignancy.

Sporadic clear cell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity

Clear cell renal cell carcinoma (CRCC) with diffuse immunoreactivity for CK7 is described. All cases of CRCC, measuring 20 mm or less in diameter over a period of 10 years, were examined. Areas of regenerative epithelial cell nests (REC) were also examined. Fifteen specimens containing 29 nodules were diagnosed as CRCC due to the characteristic clear cytoplasm. Of these 29 nodules, 21 showed diffuse CK7 positivity while eight showed CK7 negativity. The CK7 positive CRCC measured less than 16 mm and contained varying proportions of tumour cells with chromophil cytoplasm. Architecturally, CK7 positive CRCC consisted of cysts and solid cell nests with tubulo-acinar formations or papillary formations. Immunostaining for AMACR, CD10 and RCC showed negative or focal reactivity in the CK7 positive CRCC, frequently positive reactivity in CK7 negative CRCC and negative reactivity in REC which also displayed strong CK7 reactivity. The ten patients with 21 CK7 positive CRCC developed no metastatic disease over a follow up time that ranged from 1 to 10 years (mean of 3 years). CRCC characterised by diffuse CK7 positivity represents a distinct type of CRCC with characteristic histopathological and immunohistochemical features.

Intracardiac Ectopic Thyroid Carcinosarcoma in a Dog

A 13-year-old spayed female Labrador Retriever with a 1-year history of progressive exercise intolerance was diagnosed with an interventricular mass in the heart via echocardiogram. The animal's general condition progressively declined over the next 8 months, and it was euthanatized. The intracardiac mass, which protruded into the lumen of the right ventricle, was removed at necropsy and fixed in 10% buffered formalin. Histopathologic diagnosis was an ectopic thyroid carcinosarcoma based on the presence of 3 distinct neoplastic tissue types. Intermixed within the tumor were neoplastic thyroid follicles containing colloid and solid nests of thyroid follicular epithelial cells, vascular channels and clefts filled with blood and lined by neoplastic endothelium, and osteoid surrounded by spindle cells and often rimmed by large multinucleated cells. Immunohistochemical reaction for thyroglobulin was positive in the tumor cells forming the colloid-filled follicles and solid nests of epithelial cells. Neoplastic endothelium was positive for factor VIII-related antigen. The thyroid gland was located in its normal anatomic position and was histologically normal, ruling out the possibility that the intracardiac tumor was a metastatic lesion. To the authors' knowledge this is the first reported case of an intracardiac ectopic thyroid carcinosarcoma, and possibly the first ectopic thyroid carcinosarcoma in any location in any species.

Intraosseous Glomus Tumor of the Great Toe: A Case Report with Review of the Literature

We report a case of intraosseous glomus tumor that presented as a painful lesion in the distal phalanx of the left great toe in a 21-year-old male. The radiographic appearance showed a well-circumscribed osteolytic lesion, and histological examination revealed solid nests of polygonal cells surrounding branching vasculatures consistent with a glomus tumor. Partial toe amputation resulted in complete alleviation of the patient's pain. Although glomus tumors commonly occur in the distal soft tissue of the extremities, they very rarely localize to bone. To the best of our knowledge, this is the first published report of a case of intraosseous glomus tumor localized to the toe.

Basaloid Squamous Cell Carcinoma of the Esophagus: Report of Two Cases

Basaloid squamous cell carcinoma is an uncommon malignancy of the esophagus. We present two cases of basaloid squamous carcinoma of the esophagus. Both tumors histologically consisted of solid cell nests and displayed focal immunoreactivity for type IV collagen. The nests comprised pseudoglandular structures containing myxoid matrix. Transthoracic esophagectomy with lymph node dissection was performed in both patients. The patients had uneventful postoperative courses. One patient showed no evidence of recurrence or metastasis in the 6-month postoperative period, and the other patient died of lung metastasis 28 months after the primary treatment.

Tumor de colisión periampular

We report the case of a periampullary collision tumor, in which a duodenal-wall carcinoid and an adenocarcinoma of the head of the pancreas coexisted. We describe the case of a 64-year-old man with a recent history of diarrhea, who was diagnosed with obstructive jaundice. A duodeno-pancreatectomy was performed, and the specimen showed two independent neoplasms in the histopathologic study. Solid cords and nests of neuroendocrine cells in the duodenal wall formed the carcinoid tumor, whereas the other neoplasm was made up of a well-differentiated adenocarcinoma of the pancreas. Both were confirmed by immunohistochemical analysis. According to the literature reviewed, this is the sixth reported case of this rare neoplastic association.

Solid Cell Nests: Role in Thyroid Disease

Solid Cell Nests: Role in Thyroid Disease

A Spontaneously Occurring Renal Tubule Carcinoma in a Mouse

Spontaneous occurrence of renal tubule carcinoma in mice is known to be rare. The following features of this tumor are recognized as areas of hemorrhage and massive necrosis and many show atypical cells and numerous mitotic figures. The present renal tubule carcinoma developed in an untreated B6C3F1 male mouse at the age of 109 weeks. The tumor mass occupied nearly the entire renal cortex and invasion of normal renal tissue was observed. The tumor had solid cell nests, a gland-like structure, definite neovascularization and capsular invasion. The tumor cells had clear eosinophilic cytoplasm, a brush border structure and high proliferative activity. Although tumors derived from the proximal tubule reportedly show basophilic cytoplasm, the tumor cells in this mouse had clear eosinophilic cytoplasm. Consequently, the animal was diagnosed as having an unusual renal tubule carcinoma (classification: solid type). (J Toxicol Pathol 2007; 20: 253-256)

Cerebral metastasis from hepatoid adenocarcinoma of the stomach

We first report a rare case of metastasis from gastric hepatoid adenocarcinoma (HAC) to cerebral parenchyma, in a 50-year-old Chinese patient. He complained of a one-month history of a paroxysm of headache in the left temple and pars parietalis accompanied with binocular caligation caligo, insensible feeling of limbs and transient anepia. Magnetic resonance (MR) imaging revealed a spherical occupying lesion in the left posterior-temple lobe which was clinically diagnosed as a metastatic tumor. Three years ago, the patient accepted total gastrectomy as he was pathologically diagnosed at gastroscopy having an adenocarcinoma. Eight months after gastrectomy, the occupying lesion in liver was detected by ultrasound and CT, and he accepted transcatheter arterial embolization. Before operation of the brain metastasis, no obvious abnormality was found in liver by ultrasound. Histopathological characteristics of the brain tumor were identical to those of stomach tumor. The growth pattern of both tumors showed solid cell nests. The tumor cells were polygonal, and had abundant eosinophilic cytoplasm and round nuclei with obvious nucleoli. Sinusoid-like blood spaces were located between nodular tumor cells. Immunohistochemistry-stained tumor cells were positive for AFP and negative for Hep-Par-1. According to these histopathological findings, both tumors were diagnosed as HAC and metastatic HAC. The patient remained alive 16 mo after tumorectomy of the cerebral metastasis. The differential diagnosis of brain metastasis from metastatic tumors should use a panel of antibodies to avoid confusing with the brain metastasis of hepatocellular carcinoma (HCC). This paper describes this rare case of metastasis from gastric hepatoid adenocarcinoma to cerebral parenchyma, and provides a review of the literature concerning its histopathological and immunohistochemical characteristics.

Carcinoma Showing Thymus-like Differentiation of the Thyroid (CASTLE): A Comparative Study

Carcinoma showing thymus-like differentiation (CASTLE) is a rare intrathyroidal neoplasm, a member of a tumor family probably arising from ectopic thymus or branchial pouch remnants. Thyroid solid cell nests (SCNs) may also be derived from branchial pouch remnants. SCNs express p63, carcinoembryonic antigen (CEA), and high molecular weight keratin (HMWK). To determine whether CASTLE and SCNs derive from similar embryologic origins/lines of differentiation, and to better differentiate CASTLE from other thyroid neoplasms, we compared p63, CD5, HMWK, and CEA staining of CASTLE and SCNs with other thyroid and thymic lesions. Seven CASTLE, 11 SCNs, 10 thymic carcinoma, 11 invasive thymoma, 12 thymoma, 28 papillary thyroid carcinoma, 4 thyroid squamous cell carcinoma, 2 childhood sclerosing carcinoma, 4 follicular adenoma, 6 follicular carcinoma, 4 poorly differentiated carcinoma, and 20 lymphocytic thyroiditis cases were analyzed. In normal thyroid, only SCNs stained for p63, HMWK, and CEA. The only CD5-positive cells in normal thyroid were T cells. Thymomas and normal thymus stained similarly to SCNs. All CASTLE and thymic carcinomas exhibited diffuse p63 and HMWK staining and all CASTLE cases and the majority of thymic carcinomas were positive for CEA and CD5. In contrast, none of the other thyroid neoplasms examined exhibited consistent staining for all 4 markers studied. These findings provide further evidence that CASTLE is distinct from other thyroid neoplasms, is probably of thymic origin, and may arise from branchial pouch remnants, the thyroid SCNs. Moreover CD5, HMWK, CEA and p63 can be used to help distinguish CASTLE from other thyroid neoplasms.

Solid and Cystic Cell Nests

Solid and Cystic Cell Nests

Surgical Resection of Locally Advanced Granular Cell Tumor of the Orbit

We report a case of locally advanced granular cell tumor of the orbit treated by a multidisciplinary surgical approach. A 49-year-old woman with a recently biopsied granular cell tumor of the orbit was referred to our tertiary care cancer center for evaluation of a right-sided globe ptosis and a palpable mass in the right orbit that had been present for approximately two years. Magnetic resonance imaging showed a large orbital mass that extended posteriorly to the orbital apex and anteriorly to the levator and superior rectus muscle complex. A workup including computed tomography of the chest, abdomen, and pelvis did not show any metastatic foci. Surgical resection of the mass was undertaken via a frontozygomatic craniotomy supplemented by an anterior orbitotomy to repair the levator aponeurosis and the superior oblique tendon, which were partially resected with the mass. Histologic evaluation of the mass revealed solid nests of polygonal cells that had centrally located, round nuclei with abundant eosinophilic granular cytoplasm. The cytoplasmic granules were positive on the periodic acid-Schiff reaction and were diastase-resistant. Immunohistochemical staining was positive for S-100 protein. During the most recent follow-up visit six months after surgery, the patient had no clinical evidence of tumor recurrence, had minimal residual ptosis and exposure keratopathy, and had stable visual function.

Juxtaglomerular Cell Tumor of Kidney With CD34 and CD117 Immunoreactivity: Report of 5 Cases

Juxtaglomerular cell tumor is a rare renal neoplasm. Renin immunohistochemistry and electron microscopic documentation of rhomboid crystals are the primary methods of diagnosing this benign tumor. In this retrospective study, we evaluated the morphologic, immunohistochemical, and ultrastructural features of 5 cases of juxtaglomerular cell tumor to determine the effectiveness of CD34 and CD117 immunohistochemistry for the diagnosis of this tumor. We reviewed 5 cases with clinical, histologic, immunohistochemical, and ultrastructural aspects. Three women and 2 men with a mean age of 37.8 years (range, 16-60 years) were included in this study. All patients presented with severe hypertension. All tumors were well circumscribed and ranged from 1.5 cm to 8.5 cm (mean, 4.4 cm). On light microscopic examination, we found solid sheets and nests of tumor cells with oval-to-round nuclei and eosinophilic cytoplasm. Low-power microscopic examination disclosed a hemangiopericytic vascular pattern. Immunohistochemistry results were as follows: vimentin (positive), renin (weakly positive), smooth muscle actin (focal immunoreactivity), and cytokeratin (negative). All 5 tumors were immunoreactive for CD34 and CD117. Electron microscopy revealed rhomboid crystals in the cytoplasm. Postoperatively, 4 patients were normotensive and 1 patient experienced persistent mild hypertension. Our findings indicate that immunohistochemistry for CD34 and CD117 are effective at diagnosing juxtaglomerular cell tumor. Juxtaglomerular cell tumor should be considered in the diagnosis of any renal tumors with epithelioid cells and negative initial cytokeratin immunohistochemistry.

Branchial‐like cysts of the thyroid associated with solid cell nests

Presented herein is the case of a 65-year-old man with a 20 year history of thyroid hypofunction. On sonography a cystic lesion 4 x 4 x 5 cm in largest diameter was found, replacing most of the right lobe of the thyroid gland. Microscopically, the lesion was composed of labyrinth-like cystic structures (LCS) lined by a few layers of benign-appearing squamous cells and filled by mucinous material. Adjacent to the cyst walls were discontinuous patches of a lymphoid tissue, composed of haloed centrocyte-like cells or germinal centers mostly depleted of germinal cells. Additionally, there were numerous squamous cell nests equivalent to solid cell nests (SCN), all of which were surrounded by a similar-looking lymphoid tissue. Rare SCN were thus cystically changed and contained a small amount of mucus. The SCN communicated with the LCS: the former represented the most distal outpouchings of the latter. The epithelial structures were surrounded by a loose collagenous adipocytic stroma with plump fibroblasts, which resembled the stroma often seen in lateral neck cysts associated with structures such as cartilage, accessory salivary gland tissues, cysts and accessory thyroid and thymus. Immunohistochemically, all lesional elements were negative for calcitonin and thyroglobulin. The results of the paper suggest that branchial cleft-like cyst have an origin in the ultimobranchial body.

Association of Low-Grade Endometrioid Carcinoma of the Uterus and Ovary With Undifferentiated Carcinoma: A New Type of Dedifferentiated Carcinoma?

Low-grade endometrioid carcinomas, either of the endometrium or the ovaries, usually have an excellent prognosis. The association of this type of tumor with undifferentiated carcinoma is rare. In this study, we present the clinicopathologic features of 25 such cases. The age of the patients ranged from 30 to 82 years (median, 51 years). At presentation, the patients had either vaginal bleeding or pelvic pain. The endometrioid carcinoma involved the endometrium in 14 cases, the endometrium and 1 or both ovaries in 9 cases, and the ovaries in 2 cases. Undifferentiated carcinoma associated with low-grade endometrioid carcinoma was found at presentation in 19 grade 1 or 2 endometrioid carcinomas: 15 in the endometrium and 5 in the ovary. In one of these cases, undifferentiated carcinoma was found in the endometrium and the ovary. Undifferentiated carcinoma was found after resection of low-grade endometrioid carcinoma in six cases, involving the retroperitoneum, pelvis, vagina, or liver. The undifferentiated carcinoma was composed exclusively of diffuse sheets and solid nests of epithelial cells in l0 cases. Epithelial cells with isolated foci of keratinization were seen in nine cases and rhabdoid cells in a myxoid background in six cases. Twenty-four patients were treated with total abdominal hysterectomy and with bilateral salpingo-oophorectomy. Twenty-two patients received additional therapy as follows: chemotherapy (), radiotherapy (), and tamoxifen (). Follow-up showed that 15 patients died of disease in 1 to 60 months (median, 6 months), and 5 patients are alive with progressive disease with a follow-up between 6 and 8 months; 1 patient is alive with no evidence of disease at 104 months. In four cases, the diagnosis was made recently, with short follow-ups of 3 and 4 months. Foci of undifferentiated carcinoma may be confused with solid endometrioid adenocarcinoma erroneously leading to the diagnosis of a grade 3 or a significantly less aggressive grade 2 endometrioid carcinoma. The recognition of undifferentiated carcinoma in an otherwise low-grade endometrioid adenocarcinoma is extremely important because it indicates aggressive behavior. In asynchronous cases, being aware of this association can explain the absence of a second primary.

Cyclooxygenase-2 in normal, hyperplastic and neoplastic follicular cells of the human thyroid gland

This study was undertaken to investigate cyclooxygenase-2 (COX-2) expression in follicular cells of the human thyroid. COX-2 expression was studied immunohistochemically in a total of 174 samples. COX-2 immunoreactivity was confined to the cell cytoplasm with the nuclei remaining unlabelled. COX-2 expression was observed in five cases (17.2%) of normal follicular cells and in one case (16.6%) of solid cell nests. Follicular carcinoma expressed COX-2 more frequently than follicular adenoma (93.4% vs 21.1%) (p<or=0.001). A higher percentage of cases of papillary microcarcinomas up-regulated COX-2 in comparison with all papillary carcinomas (p<or=0.05). However, we could not establish any relationships among COX-2, patients' ages or lymph node metastases in papillary carcinomas. COX-2 expression was found in 12 (92.3%) poorly differentiated carcinomas and in 13 (92.8%) undifferentiated carcinomas. We found that COX-2 is not always useful as a marker of malignancy. Our results suggest that COX-2 plays a role in progression of all thyroid carcinomas, but in papillary carcinomas, seems more important only in the early stages. COX-2 expression in the undifferentiated carcinoma deserves special consideration due to its prognosis and to the fact that selective COX-2 inhibitors were found to enhance tumour response to radiation in some studies.

Epithelioid cellular chordoma of the sacrum: a potential diagnostic problem

We describe a sacral chordoma composed of solid nests of epithelioid cells. The tumor originated in the presacral area. Extensive clinical workup did not reveal any other lesion in the patient. In contrast to typical chordomas, this tumor contained only rare physaliferous cells, had no myxoid stroma, and was immunohistochemically unreactive with the antibody to S-100. The diagnosis of chordoma was supported by electron microscopy, which showed that the tumor cells contained numerous mitochondria surrounded by profiles of rough endoplasmic reticulum. The abundance of mitochondria, the narrow intercellular spaces, combined with a lack of glycogen, and a lack of extracellular myxoid material accounted for the epithelioid appearance of the tumor. We report this case to point out that the cellular chordomas can appear epithelioid in the sacrum and they may resemble metastatic squamous or transitional cell carcinomas.

Cystic Tumor of the Atrioventricular Node of the Heart Appears to Be the Heart Equivalent of the Solid Cell Nests (Ultimobranchial Rests) of the Thyroid

We studied a series of 10 solid cell nests (SCNs) of the thyroid and a case of cystic tumor of the atrioventricular node (CTAVN) of the heart and reviewed the literature. The CTAVN and SCNs appeared as cystic and/or solid (squamoid) structures mainly composed of polygonal or oval cells (main cells) admixed with occasional clear cells (neuroendocrine and C cells). Main cells were immunoreactive for simple and stratified epithelial-type cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, carbohydrate antigen 19.9, p63, bcl-2, and galectin-3. Neuroendocrine (and C) cells were positive for simple-type cytokeratins, carcinoembryonic antigen, calcitonin, chromogranin, synaptophysin, and thyroid transcription factor-1. Our data support the hypothesis that the CTAVN of the heart and the SCNs of the thyroid are identical structures that represent the same lesional process. The assumption that CTAVN is a ultimobranchial heterotopia fits with the known role of cardiac neural crest cells in cardiovascular development.