Solid Cell Nests Research Articles

Pseudoinvasion and squamous metaplasia/morules in colorectal adenomatous polyp: a case report and literature review

BackgroundSubmucosal pseudoinvasion and squamous metaplasia (SM) are incidental and special morphological findings in colorectal adenomas, and both can mimic invasive carcinoma. The coexistence of these two findings further increases the risk of misdiagnosis, posing a great diagnostic challenge to pathologists. From 1979 to 2022, only 8 cases have been reported, which was extremely rare. In this report, we presented a case of sigmoid colon adenoma accompanied by pseudoinvasion and SM. Additionally, relevant literature was analyzed to summarize the clinical and pathological characteristics.Case presentationA 51-year-old Chinese male patient presented with fresh blood after defecation. Electronic colonoscopy revealed multiple polyps, which were removed using a snare and subjected to high-frequency electrocoagulation resection. The largest polyp, located in the sigmoid colon, was a thick pedunculated and lobulated polyp with a maximum diameter of 2.8 cm. The surface of the polyp showed slight ruggedness and redness, and it was sent for pathological examination. Grossly, the polyp had a lobulated and slightly rough surface. Microscopically, it showed a tubulovillous adenoma with focal high-grade dysplasia and mucosal muscle hyperplasia. Glandular elements were observed in the submucosal layer, forming a well-defined lobular structure. Some of the glands displayed cystic change, and focal SM could be seen within the adenoma. SM could manifest as discrete solid cell nests of varying sizes or cribriform-morular-like structures. Immunohistochemical staining showed that SM cells were diffusely positive for cytokeratin 5/6 (CK5/6); p40, p63, and cytokeratin 20 (CK20) were negative; while caudal type homeobox 2 (CDX2) was weakly positive. β-catenin showed abnormal nuclear expression, and an extremely low Ki67 proliferation index was observed.ConclusionsCoexistence of SM and pseudoinvasion in colorectal adenomas is highly rare. It is more commonly observed in males and tends to occur in the sigmoid colon. It primarily manifests in tubulovillous adenoma and tubular adenoma, with a majority of cases exhibiting a pedicle. Histologically, it is similar to invasive lesions. The cystic dilation of the submucosal glands, hemosiderin deposition, and the presence of a lamina propria around the submucosal glands without adjacent desmoplastic reaction, suggest pseudoinvasion rather than cancer. The bland cytological morphology and Immunohistochemical markers play a crucial role in distinguishing SM from true invasive lesions.

Clear Cell Carcinomas of Müllerian Type and Rete Testis Origin Presenting as Scrotal Masses: A Study of Seven Cases.

Ovarian-type epithelial tumors involving the testis and paratestis are rare, with clear cell carcinomas (CCC) one of the least frequent. We report our experience with 4 müllerian-type (MT) CCCs presenting as testicular/scrotal masses and arising in the paratestis (n=2) and seminal vesicle (n=2; well supported in 1 case and likely in the other). In addition, we document 3 cases of papillary CCC exclusively within the rete testis (RTCCC) and seminiferous tubules and differing from the MT tumors. The patients with MTCCC were 24 to 85 years old (median, 42y), and 2 had metastases at presentation. The 2 originating in the paratestis were associated with other MT tumors, an endometrioid borderline tumor and a papillary serous borderline tumor. The other 2 MTCCCs likely involved the testis via extension from seminal vesicle primaries through the vasa deferentia. All MTCCCs showed typical features, including tubules, simple papillae with hyalinized cores, and solid nests of polygonal clear cells with occasional hobnail features. Both paratesticular primaries showed sarcomatoid foci with tumor-associated neutrophilic infiltrates. The 3 RTCCCs presented in 54-, 57-, and 60-year-old men as testicular masses; they showed intrarete arborizing papillary growth with nonhyalinized fibrous cores and piled-up, solid foci, lacked hobnail cells, and expressed carbonic anhydrase IX (2/2) and CD10 (2/2) but not CA125, unlike the MTCCCs. On follow-up, 2 patients with MTCCC died of metastatic tumor (4 and 13.5mo), a third developed ileal and retroperitoneal metastases at 13 months; and the fourth died at 13.5 months of unspecified cause. Follow-up of 2 patients with RTCCCs showed 1 disease free at 8 months and another alive with unknown disease status at 13 years. We conclude that CCCs involving the testis may either be of MT with often aggressive courses or show some features of renal tumors, with confinement to the rete testis and indolent behavior.

Mucoepidermoid Carcinoma of the Thyroglossal Duct: Two Rare Entities in a Unique Case Report.

Mucoepidermoid Carcinoma (MEC) of the thyroid represents less than 0.5% of all thyroid neoplasms. Thyroglossal duct cyst carcinoma is a rare condition with only approximately 300 cases reported. A 34-year-old pregnant woman at 37 weeks gestation presented to an endocrinological center for primary autoimmune hypothyroidism. The thyroid ultrasound revealed a pseudonodular pattern. The patient was followed up after two years. She reported a full-term delivery without complications. A new thyroid ultrasound was performed, showing a cystic lesion in the median suprathyroid area, measuring 6 x 9 x 10 mm, not previously reported. After 4 months, the suprathyroid cystic lesion was confirmed by thyroid ultrasound, measuring 6 x 11 x 12 mm. The patient was referred for fine-needle aspiration cytology. Cytological examination showed lymphocytes, red blood cells, and some epithelial aggregates with large cytoplasm and nuclear polymetrism with oxyphilic aspects. The patient underwent the Sistrunk procedure for the suprathyroid lesion. The histological examination revealed lymphocytic thyroiditis in heterotopic thyroid tissue with solid cell nest, epidermoid epithelium, and mucus-secreting cells suggestive of low-grade mucoepidermoid carcinoma. The immunohistochemistry study was positive, exhibiting thyroid transcription factor 1 and cytokeratin-19. No positivity was observed for thyroglobulin, calcitonin, galectin-3, and Hector Battifora mesothelial antigen 1. The recent follow-up examination, 13 months after the surgery, has been found negative for disease recurrence. This is the first case of an MEC occurring within a thyroglossal duct. Considering the age of the patient, the histological diagnosis, and the absence of thyroid nodules and metastasis, we decided on the Sistrunk procedure without total thyroidectomy.

Pseudosquamous Adenocarcinoma of the Lung: Clinicopathologic and Immunohistochemical Study of 10 Cases.

Pseudosquamous adenocarcinoma of the lung is an unusual morphologic variant of poorly differentiated non-small cell lung carcinoma that superficially resembles a squamous cell carcinoma. We have examined 10 cases of these tumors in 4 women and 6 men, aged 47 to 93 years. The tumors were all peripheral and measured from 1.5 to 5.5cm. All cases were characterized by solid nests of large polygonal tumor cells containing atypical nuclei with abundant cytoplasm and sharp cell borders, adopting a pavement-like architecture that simulated squamous cell carcinoma. Some cases demonstrated intracytoplasmic hyaline inclusions suggestive of keratinization. The nests of tumor cells often showed central comedo-like areas of necrosis. Intercellular bridges were not seen in any of the cases. The tumors often displayed marked clearing of the cytoplasm enhancing their epidermoid appearance. In 4 cases, the solid pseudosquamous areas were seen to merge with a focal lepidic adenocarcinoma component, and in 1 case, abortive microscopic foci of acinar differentiation were also noted within the tumor. One case showed focal sarcomatoid spindle cell areas. The tumor cells were negative for p40 and CK5/6 and labeled with TTF1 or Napsin-A, confirming an adenocarcinoma phenotype. Clinical follow-up information was available in 8 patients; 6 patients died of their tumors between 6 months to 11 years after diagnosis (mean: 3.1y). One patient died of complications related to surgery and one patient with a low-stage tumor died at 27 years from other causes. Solid pattern adenocarcinomas can be confused for squamous cell carcinoma and may require immunohistochemistry to determine their true phenotype.

Association between pathological infiltrative tumor growth pattern and prognosis in patients with resected lung squamous cell carcinoma

IntroductionLung squamous cell carcinoma (LUSC) usually shows expansive growth with large tumor nests; few reports on invasive growth patterns (INF) in LUSC have been associated with poor prognosis in gastrointestinal and urothelial cancers. In this study, we examine the association between INF and the prognosis of LUSC. Materials and methodsWe analyzed INF as a potential prognostic factor in 254 consecutive patients with LUSC who underwent complete surgical resection at our hospital between 2008 and 2017. INF was classified into 3 categories based on the structure of the tumor other than the large round solid nest of tumor cells. ResultsINF was categorized as INFa in 59 patients (23 %) with only well-demarcated large solid tumor cell nests, INFb in 89 patients (35 %) with medium to small, alongside large solid nests, and INFc in 98 patients (39 %) with cord-like/small nests or isolated cells plus large or medium solid nests. No significant lymph node metastasis differences were observed between INFc and INFa/b tumors. However, in patients with p-stage I, INFc had a poorer prognosis with regard to recurrence-free survival (RFS), with a 5-year RFS rate of 53.3 %, compared to 74.9 % for INFa/b (p = 0.010). ConclusionOur study highlights a novel pathological concept of INF in LUSC, and contributed to the proposal that it is a factor indicating an unfavorable prognosis in patients with early-stage LUSC. A prospective multicenter study is warranted for INFc patients, as careful follow-up and adjuvant chemotherapy might lead to the early detection and prevention of recurrence.

Ought to The Changes Within the Immunophenotype of Solid Cell Nests (SCNs) and Follicular Cells in Hashimoto's Thyroiditis be Considered as Premalignant Lesions?

Papillary thyroid carcinoma (PTC) is more frequently reported in patients with Hashimoto's thyroiditis (HT), which may be associated with the presence of solid cell nests (SCNs) and focal PTC-like nuclear alterations in the thyroid gland. The point of this consideration was to assess the morphological and immunohistochemical features of SCNs and follicular epithelial changes in Vietnamese patients with HT. Hematoxylin-eosin and immunohistochemistry were performed on 20 samples of HT patients who underwent thyroidectomy and were diagnosed with Hashimoto's thyroiditis at Military Medical Hospital 103 from 6/2018 to 6/2019. The expression of five markers (P63, Calcitonin, TTF1, CK19 and HBME-1) in SCNs and follicular epithelial changes were evaluated. Ninety per cent of samples had SCNs with an average of 10 SCNs per section. Only type 1 and type 4 SCNs were presented (85% and 55%, respectively) and all SCNs were composed of main cells (p63-positive). Fifteen of the 18 cases having SCNs possessed nuclear features of PTC. C-cell hyperplasia was found in one case with 20 clusters. All SCNs showed strong staining with CK19 and weak staining with HBME-1. Follicular epithelial changes were Hürthle cell metaplasia, PTC-like nuclear alterations, atypical solid nodules, papillary and glomerular-like forms (40%, 100%, 25% and 50%, respectively). Follicular cells of glomerular-like forms (new alteration) especially were positive with CK19 (2+ ~ 3+), HBME-1 (1+) and TTF1, while the components in these follicles were negative with CK19, HBME-1 and TTF1. Among PTC-like nuclear alterations, all the atypical solid nodules related to HT showed markers related to PTC and without SCNs. Increasing the number of SCNs, as well as PTC-like nuclear alterations of main cells in SCNs and follicular epithelial changes were co-expressed CK19 and HBME-1. Therefore, the need for HT management should be considered.

Inmixed and Bellicose-Adenosquamous Carcinoma-Uterine Cervix

Adenosquamous carcinoma of uterine cervix is a preponderantly high grade neoplasm configured of admixed glandular articulations and squamous epithelium wherein glassy cell carcinoma emerges as an exceptional, aggressive variant. Adenosquamous carcinoma is posited to arise from sub-columnar reserve cells confined to endocervical basal epithelium. Cytological smears depict papillary articulations admixed with bland columnar epithelial cells and high grade squamous intraepithelial lesion. The biphasic tumour is composed of well defined, malignant components of glandular articulations and poorly differentiated squamous epithelium. Glassy cell carcinoma demonstrates solid cell nests comprised of pleomorphic, polygonal tumour cells pervaded with glassy, eosinophilic cytoplasm, enlarged, eosinophilic nuclei, prominent nucleoli and distinct cytoplasmic membrane. Neoplastic cells appear enmeshed within an intense inflammatory cell infiltrate with significant eosinophils. Glassy cell carcinoma appears immune reactive to MUC1, MUC2, epithelial membrane antigen (EMA), CAM5.2 or p63 with focal immune reactivity to carcinoembryonic antigen (CEA). Adenosquamous carcinoma requires segregation from neoplasms such as adenocarcinoma with coexisting squamous intraepithelial lesion (SIL), adenoid basal carcinoma, cervical extension of endometrial adenocarcinoma, and squamous cell carcinoma with focal mucin droplets, large cell non keratinizing squamous cell carcinoma or lymphoepithelioma-like carcinoma. Tumefaction may be appropriately treated by radical abdominal hysterectomy followed by adjuvant chemotherapy and radiation therapy.

Tubuloductal/syringoid variant of central odontogenic fibroma with amyloid?

<h3>Introduction</h3> Glandular tumors of jaw bones present, most often, histopathologic features of salivary gland and, rarely, of cutaneous glandular neoplasms and are thought to predominantly originate from odontogenic epithelium. <h3>Materials and Methods</h3> An unusual maxillary tumor in a 74-year-old male is presented exhibiting radiolucency and root resorption in the apical area of teeth #6-7. <h3>Results</h3> Preparations revealed occasionally branching tubular cords and ductal structures characterized, mostly, by a bilayer composed of luminal Ber-EP4, cytokeratin (CK) 7 and occasionally CK8/18 positive cells and varying from cuboidal to low columnar, and abluminal, CK5/6 positive, basal/basaloid cells revealing nuclear reactivity for p63/p40. Smooth muscle actin and calponin were negative, save for a single focus for calponin, confirming absence of myoepithelial support or epithelial mesenchymal transition. CK19 exhibited staining of both layers, the luminal being more intense. Eosinophilic secretory material and, occasionally, a luminal pellicle were decorated with CK8/18 and polyclonal carcinoembryonic antigen (CEA). CD1a identified only rare Langerhans' cells and Ki67 decorated 1-2% of abluminal cell nuclei. Small solid nests of epithelial cells were also present. Infrequently, an apparent transition of a nest into a tubular structure was appreciated. The partially inflamed stroma featured multiple hyalinized acellular deposits consistent with amyloid, as confirmed by bright orange Congo red reactivity with apple-green birefringence, which reacted with antibodies against odontogenic ameloblast-associated (ODAM) protein but not amelotin and secretory calcium-binding phosphoprotein proline-glutamine rich 1. <h3>Conclusions</h3> Based on the above the diagnosis of tubuloductal/syringoid variant of central odontogenic fibroma with ODAM amyloid is favored.

Solitary, subcutaneous, fixed, firm, and fast-growing nodule

Solitary, subcutaneous, fixed, firm, and fast-growing nodule

Morphological, histological and ultra-structural studies on the ultimobranchial body of goat (Capra hircus).

Ultimobranchial body (UBB) remnant was considered as an enigma till the last few years, then it was recognized as a necessary organ where it is the origin of the parafollicular cells. The samples were fixed and processed for the histological and electron microscopic examination. Macroscopically, the UBB remnant appeared as a white mass at the end of the cranial one-third of the thyroid lobe. It was composed of solid cell nest, cluster of cells and small thyroid follicles. Transmission electron microscope showed some round cells containing euchromatic nuclei, numerous parafollicular cells with darkly stained granules and paler ones. It also showed some mast cells with heterochromatic nuclei and large darkly stained granules. The parafollicular cells were distributed throughout the thyroid gland but concentrated within the UBB remnant. To our knowledge, our findings represent very unique histological manifestations specially the ultra-structural ones which revealed an original finding about the new clear type of cells suggested to be a UBB remnant and ensure those of the light microscope.

Low-Grade Oncocytic Tumor of Kidney: A Distinct Emerging Entity in Renal Oncocytic Neoplasms with Diagnostic Challenge in An Old Female: A Case Report

Low grade Oncocytic Tumor (LOT) is an emerging category in renal tumors having oncocytic morphology. It has overlapping features with Renal Oncocytoma and Eosinophilic variant of Chromophobe Renal Cell Carcinoma. LOT typically shows solid nests of cells with oncocytic cytoplasm and uniform round to oval nuclei with a CK7 positive/ CD117 negative immunophenotype. Pathogenesis is not well-understood, however, variations in mTOR pathway related genes have been described. The clinical course is indolent. Here, we present the case a 64-year-old female patient who presented with a solid enhancing mass in right kidney with the clinical impression of Renal cell carcinoma. Right radical nephrectomy was performed, and histologic features were consistent with LOT.

Solid Cell Nests Hyperplasia (Ultimobranchial Body Remnants) of the Thyroid: A Pitfall

Abstract Introduction/Objective Solid cell nests (SCN) are small epithelial cell nests interspersed within thyroid parenchyma, resembling squamous/transitional epithelium. SCNs, which are ultimobranchial remnants, are popularly considered pluripotent stem-cells responsible for developing follicular and C-cells. While SCNs are not an uncommon incidental findings in thyroid, solid cell nest hyperplasia is rare. SCNs are often mistaken for benign entities such as C-cell hyperplasia (CCH) or malignant lesions such as papillary thyroid carcinoma (PTC), metastatic squamous cell carcinoma, or medullary thyroid microcarcinoma (MTC). Methods/Case Report To reiterate this diagnostic dilemma, we present a case of a 57-year-old male with a six-year history of Hashimoto thyroiditis and multiple bilateral thyroid nodules. Ultrasonography revealed two nodules, one in each lobe, measuring 2.0x1.9x1.8cm(right) and 1.6x1.5x1.5cm(left). Both were solid, hypoechoic nodules with smooth margins and no echogenic foci. Fine-needle aspiration of right nodule was suspicious for follicular neoplasm, Hürthle- cell type, and the left nodule was atypia of unknown significance. Right-hemithyroidectomy specimen revealed follicular adenoma and oncocytic adenomatous nodules in a background of florid lymphocytic thyroiditis (Hashimoto). In two blocks, small solid nests of cells were identified, largest focus measuring 0.5 cm. The cells were polygonal to epithelioid with moderate amphophilic cytoplasm. Nuclei were centrally located, irregular to oval with occasional grooves. While nests had a squamoid appearance, they did not have intercellular bridges. Although nuclear grooves and evenly dispersed chromatin and chromocenters were noted, they lacked optical clearing or intra-nuclear inclusions characteristic for PTC. Thus, excluding these two possibilities, primary diagnostic considerations were SCN versus CCH. Immunohistochemical analysis showed cells positive for P63 and CK5/6 and negative for PAX-8, TTF-1, thyroglobulin, CEA, and calcitonin. Results (if a Case Study enter NA) NA Conclusion If wrongly diagnosed as CCH, patients may be placed in a high-risk category for possible development of MTC. It is, thus, necessary to be aware of SCN, which can occasionally become hyperplastic, to prevent misdiagnosis.

An Unusual Maxillary Tumor with Tubuloductal Epithelial Structures, Solid Epithelial Nests and Stromal Odontogenic Ameloblast-Associated Protein Deposits. Tubuloductal/Syringoid Variant of Central Odontogenic Fibroma with Amyloid?

Glandular tumors of jaw bones present, most often, histopathologic features of salivary gland and, rarely, of cutaneous glandular neoplasms. They are thought to originate from odontogenic epithelium. An unusual maxillary tumorpresenting as a radiolucencyin the periapicalarea of the right permanent lateral incisor of a 74-year-old male is presented causingroot resorption. Preparations revealed occasionally branching tubular cords and ductal structures characterized, mostly, by a bilayer composed of luminal cuboidal to low columnarcytokeratin (CK) 7, Ber-EP4 and occasionally CK8/18 positive cells, and abluminal, CK5/6 positive, basal/basaloid cells revealing nuclear reactivity for p63/p40. Smooth muscle actin and calponin were negative, save for a single focus of calponinpositive cells, confirming absence of myoepithelial support or epithelial mesenchymal transition. CK19 exhibited staining of both layers, the luminal being more intense. Eosinophilic secretory material and, occasionally, a luminal pellicle were decorated with CK8/18 and polyclonal carcinoembryonic antigen (CEA). CD1a identified only rare Langerhans' cells and Ki67 decorated 1-2% of abluminal cell nuclei. Small solid nests of epithelial cells were also present. Infrequently, an apparent transition of a nest into a tubular structure was appreciated. The partially inflamed stroma featured multiple hyalinized acellular deposits consistent with amyloid, as confirmed by bright orange Congo red reactivity with apple-green birefringence, which reacted with odontogenic ameloblast-associated (ODAM) protein antibody but not with antibodies for amelotin and secretory calcium-binding phosphoprotein proline-glutamine rich 1. Based on the above, the diagnosis of tubuloductal/syringoid variant of central odontogenic fibroma with ODAM amyloid is favored.

Primary lymphoepithelioma-like carcinoma of the esophagus with metastatic lymph node and gastric cancer.

Upper gastrointestinal lymphoepithelioma-like carcinoma (LELC) is a rare disease-especially esophageal LELC (ELELC). Here, we report a surgically treated case of ELELC with gastric carcinoma. The patient was a 68-year-old asymptomatic Japanese man. Endoscopy revealed a submucosal-like protruding tumor located in the anterior wall of the esophagus 31-33cm from the upper incisors and a slightly ulcerative lesion at the antrum of stomach. Histopathological diagnosis from biopsy of the esophageal lesion revealed a poorly differentiated squamous cell carcinoma; the stomach lesion was found to be well-differentiated tubular adenocarcinoma. CT showed a swollen lymph node along the left recurrent nerve. On the basis of a diagnosis of esophageal and gastric cancer, we performed esophagectomy with three-field lymph node dissection and partial gastrectomy. Histopathology of the resected esophageal tumor revealed solid nests of cancer cells, with substantial infiltration of lymphoid cells into the stroma. There were poorly differentiated cancer cells with large nuclei in the lymph node. In situ hybridization for Epstein-Barr virus showed no nuclear signal in the tumor cells. Immunohistochemistry gave a diagnosis of ELELC.

High-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical Significance.

High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.

The Minimalistic Metamorphoses-Adamantinoma

Adamantinoma is an exceptional, primary, malignant, low-grade bone, biphasic, fibro-osseous bone neoplasm of uncertain origin typically constituted of epithelial articulations embedded within a mesenchymal or osteofibrous dysplasia-like stroma. Adamantinoma commonly arises within diaphysis and metaphysis of tibia in addition to ulna, femur, fibula, humerus, radius, ribs, tarsal and metatarsal bones. Adamantinoma depicts a repetitive mutation of KMT2D (MLL2) gene along with fusion of somatic gene EPHB4-MARCH10. Expression of DLK1 gene is enhanced. Adamantinoma is subdivided into diverse categories such as classic subtype, osteofibrous dysplasia-like or differentiated adamantinoma and dedifferentiated adamantinoma. The neoplasm is comprised of epithelial cells with minimal atypia disseminated within an osteofibrous dysplasia -like stroma. Solid nests of basaloid cells with peripheral palisading, tubular structures, clusters of keratinized squamous epithelium or fascicles of spindle-shaped cells are exemplified.

A case of cribriform carcinoma of the skin: a newly described rare condition.

Primary cribriform carcinoma of the skin is an indolent, rare, adnexal tumor. Although its malignant potential remains uncertain, no recurrence or metastasis has been reported. A 33-year-old man presented with a solitary, erythematous, subcutaneous nodule on the right knee. The clinical impression was epidermal cyst, and the resected tumor demonstrated a well-circumscribed mass in the dermis and subcutis. The tumor was composed of two regions: a solid component and a cribriform component. The solid component (90%) showed multiple solid nests of epithelial cells. Individual cells had large, oval-to-round, hyperchromatic, pleomorphic nuclei with a nuclear groove. The cribriform component (10%) showed similar neoplastic cells with many prominent lumina. Some lumina had an eosinophilic substance that exhibited a positive periodic acid-Schiff reaction. No recurrence or metastasis was observed within a follow-up period of eight months after excision. In conclusion, we report the first case of primary cribriform carcinoma of the skin in Korea.

S2880 A Rare Cause of Melena

INTRODUCTION: Melanoma presenting in the gastrointestinal tract is commonly due to metastasis from a primary cutaneous or ocular lesion. There have been a few case reports of primary GI melanoma which is most commonly seen in the rectum and anus. We report a case of a 77 year old man who presented with GI bleeding and was found to have a primary small bowel melanoma. CASE DESCRIPTION/METHODS: A 77-year-old male presented with generalized weakness and a remote history of melena for the past week. Physical exam was unremarkable with no palpable masses or abdominal tenderness. Labs were significant for iron deficiency anemia with a hemoglobin of 8.9 from 13.1 and a ferritin of 14 ng/ml. Patient underwent bidirectional endoscopy which showed no clear source for iron deficiency anemia. A capsule endoscopy was performed, and a mass with overlying ulcerated mucosa was seen in the small bowel (Figure 1). Subsequent computed tomographic enterography demonstrated a 3.3 cm soft tissue mass in the jejunum (Figure 2). As the mass was unable to be reached endoscopically, the patient underwent laparoscopic removal of the mass, and pathology was most consistent with malignant melanoma. Histology showed solid nests of epithelioid cells with brisk mitotic activity, and immunohistochemistry staining was positive for SOX-10 (Figure 3), a marker of melanocyte differentiation. The patient underwent a skin exam showing no evidence of a cutaneous primary melanoma, and a fundoscopic exam showed no evidence of ocular melanoma. A PET scan did not identify an alternative site of primary malignancy or any other sites concerning for metastatic disease. As the patient had a solitary lesion in the small bowel without evidence of an alternative primary melanoma, the final diagnosis was primary malignant melanoma of the jejunum. At one year follow up, patient did not have any recurrence noted on imaging. DISCUSSION: While melanoma is the most common tumor to metastasize to the GI tract, small intestinal primary melanoma is extremely rare making up 2.3% of primary GI melanomas. In all cases where melanoma is found in the GI tract, a comprehensive evaluation for additional metastatic lesions and alternative primary site with a skin exam, fundoscopic exam and PET scan is indicated. Primary GI melanoma is a rare clinical entity with nonspecific symptoms that requires a high index of suspicion and a thorough workup for a primary source when diagnosed.Figure 1.: Mass with overlying ulcerated mucosa in the small bowel on capsule endoscopy.Figure 2.: 3.3 cm soft tissue mass in the jejunum on computed tomographic enterography.Figure 3.: Immunohistochemistry staining of jejunal mass was positive for SOX-10, a marker of melanocyte differentiation.

Clinicopathologic Study of Gleason Pattern 5 Prostatic Adenocarcinoma With "Single-cell" Growth Reveals 2 Distinct Types, One With "Plasmacytoid" Features.

Each Gleason score category of prostatic adenocarcinoma (or Grade Group) may encompass a diverse group of architectural patterns such as well-formed glands, poorly formed glands, cribriform structures, single cells, and/or solid sheets. We have noted heterogeneity within the single-cell subtype of Gleason pattern 5 prostatic adenocarcinoma that has not been fully addressed. Therefore, we retrospectively reviewed a series of radical prostatectomies with high-grade prostatic adenocarcinoma (Grade Group 4 or 5), identifying tumors with a component of single-cell infiltration. Additional cases identified prospectively were also included. TNM status, association with other histologic patterns, and clinical follow-up status were determined. Immunohistochemistry for NKX3.1, E-cadherin, p120 catenin, and prostate-specific antigen (PSA) were performed in each case. Eighteen cases with a component of well-developed Gleason pattern 5 characterized by single infiltrative cells that comprised ≥5% of the tumor were identified (15/202 retrospective radical prostatectomies with the high-grade disease [7.5%]). The single-cell pattern ranged from 5% to 50% of the tumor volume, with 5 cases containing ≥40%, and variable secondary architecture included diffuse infiltrating single cells with targetoid growth pattern around benign glands, solid expansive nests of noncohesive cells, and corded/single file growth pattern. Further morphologic analysis demonstrated 2 distinct histologic subtypes: (1) (subtype 1; n=9) monomorphic "plasmacytoid" tumor cells with eccentrically placed nuclei and variable intracytoplasmic vacuoles with bland cytology and discohesion and (2) (subtype 2; n=9) more cohesive tumor cells with greater cytologic atypia characterized by prominent nucleoli, greater variability in nuclear size/shape, occasional mitotic figures, and more irregular infiltration. By immunohistochemistry, NKX3.1 nuclear expression and PSA cytoplasmic expression was retained in all cases. Concomitant membranous E-cadherin loss and strong cytoplasmic p120 catenin expression were present in 5 of the 18 (28%) cases, all in subtype 1 (5/9, 56%). Overall, 56% (10/18) of patients had advanced-stage disease (≥pT3b), and 70% (7/10) of these patients had associated lymphovascular invasion. All patients had concomitant cribriform patterns of carcinoma. The outcome was available for 14 patients: 4 died of unknown cause; 6 had biochemical recurrence with distant bone metastasis in 5 of the 6; and 4 patients with <3 years of follow-up currently have undetectable serum PSA levels (2 patients received salvage radiotherapy with androgen deprivation and 2 remain on routine follow-up). In summary, the single-cell pattern of Gleason pattern 5 prostatic adenocarcinoma is uniformly associated with other high-risk histologic patterns (eg, cribriform growth), and high-stage disease with distant metastasis is not uncommon. Our data suggest that the "single-cell" Gleason pattern 5 prostatic adenocarcinoma contains 2 distinct subtypes. Somatic CDH1 alterations may play a role in the development of the "plasmacytoid" pattern characterized by monomorphic cytology with concomitant E-cadherin loss and aberrant p120 catenin expression.

Malignant teratoid tumor of the thyroid gland: an aggressive primitive multiphenotypic malignancy showing organotypical elements and frequent DICER1 alterations\u2014is the term \u201cthyroblastoma\u201d more appropriate?

Primary thyroid teratomas are exceedingly rare. Mature and immature variants recapitulate their gonadal counterparts (predilection for infants/children, triphasic germ layer differentiation, and favorable outcome). On the other hand, the so-called malignant teratomas affect predominantly adults and elderly, are highly aggressive, and, according to a few published cases, harbor DICER1 mutations. We describe three highly aggressive sporadic malignant teratoid thyroid tumors in 2 females (17 and 45 years) and one male (17 years). Histology showed triphasic neoplasms composed of solid nests of small primitive monomorphic cells embedded in a cellular stroma with primitive immature rhabdomyosarcoma-like (2) or pleomorphic sarcoma-like (1) phenotype. The third component was represented by TTF1+/PAX8+ primitive teratoid epithelial tubules reminiscent of primitive thyroid follicles and/or Wilms tumor, admixed with scattered respiratory- or enteric-type tubules, neuroepithelial rosettes, and fetal-type squamoid nests. Foci of cartilage were seen in two cases, but none contained mature organoid adult-type tissue or skin adnexa. SALL4 was expressed in the small cell (2) and stromal (1) component. Other germ cell markers were negative. Molecular testing revealed a known “hotspot” pathogenic DICER1 mutation in two cases. In addition, case 1 had a missense TP53 variant. This type of thyroid malignancy is distinct from genuine teratomas. The immunoprofile suggests primitive thyroid- or branchial cleft-like differentiation. Given that “blastoma” is a well-accepted terminology in the spectrum of DICER1-associated malignancies, the term “thyroblastoma” might be more convenient for these malignant teratoid tumors of the thyroid gland. Relationship of thyroblastoma to the DICER1 syndrome remains to be addressed.