Small Cell Pattern Research Articles

Small cell pattern of ALK-negative anaplastic large cell lymphoma with double-hit rearrangements of DUSP22 and TP63.

In ALK-negative anaplastic large cell lymphoma (ALCL), gene rearrangements of DUSP22 and TP63 are considered mutually exclusive. The former predicts a favorable prognosis, while the latter is generally unfavorable. We report the first case of ALK-negative ALCL in a leukemic phase with small cell pattern transformation, harboring double-hit rearrangements of the DUSP22 gene by inv(6)(p25q21) and TP63 gene by TBL1XR1-TP63 inversion. Despite the resistance to chemotherapies, the patient remained in remission with allogeneic stem cell transplantation over 20months. Recognizing this pathologically and genetically rare condition is needed for prompt diagnosis and therapeutic decision-making in ALK-negative ALCL.

Small cell neuroendocrine carcinoma and poorly differentiated rhabdomyosarcomas of the urinary bladder in adults—A comparative analysis in favor of a common histogenesis

Rhabdomyosarcoma (RMS) of the urinary bladder in adults and elderly is an exceptionally rare neoplasm that displays poorly differentiated solid (alveolar-like) small cell pattern, frequently indistinguishable from small cell neuroendocrine carcinoma (SCNEC). However, the histogenesis of RMS and SCNEC and their inter-relationship have not been well studied and remained controversial. We herein analyzed 23 SCNEC and 3 small round cell RMS of the bladder for neuroendocrine (synaptophysin + chromogranin A) and myogenic (desmin + myogenin) marker expression and for TERT promoter mutations. In addition, the RMS cohort and one SCNEC that was revised to RMS were tested for gene fusions using targeted RNA sequencing (TruSight Illumina Panel which includes FOXO1 and most of RMS-related other genes). Overall, significant expression of myogenin and desmin was observed in one of 23 original SCNEC justifying a revised diagnosis to RMS. On the other hand, diffuse expression of synaptophysin was noted in 2 of the 4 RMS, but chromogranin A was not expressed in 3 RMS tested. TERT promoter mutations were detected in 15 of 22 (68%) SCNEC and in two of three (67%) assessable RMS cases, respectively. None of the four RMS cases had gene fusions. Our data highlights phenotypic and genetic overlap between SCNEC and RMS of the urinary bladder. High frequency of TERT promoter mutations in SCNEC is in line with their presumable urothelial origin. In addition, the presence of TERT promoter mutation in 2 of 3 RMS and lack of FOXO1 and other gene fusions in all 4 RMSs suggest a mucosal (urothelial) origin, probably representing extensive monomorphic rhabdomyoblastic transdifferentiation in SCNEC.

Transformation of recurrent ALK-positive anaplastic large-cell lymphoma from common pattern to composite pattern (lymphohistiocytic and small-cell pattern) with a change in CD30 expression.

ALK-positive anaplastic large-cell lymphoma (ALK + ALCL) is characterized by expression of ALK and CD30. The current World Health Organization (WHO) classification recognizes five morphologic patterns: common, small-cell, lymphohistiocytic, Hodgkin-like, and composite. There are few reports about the morphologic transformation of ALK + ALCL. Today, we report an intriguing case of presumed transformation from common-pattern to composite-pattern (lymphohistiocytic and small-cell pattern) ALK + ALCL, with CD30 expression changing from positive to negative. This case expands understanding of morphologic transformation between different subtypes of ALK + ALCL and highlights common diagnostic pitfalls, including atypical morphology and negative CD30. Morphologic transformation of ALK + ALCL should be assigned importance, and comprehensive clinical history, histologic and immunophenotypic evaluation are vital to rendering the correct diagnosis of ALK + ALCL.

Malignant melanoma with features of the small cell variant: A case report

Malignant melanoma can exhibit various cytomorphological features. Small cell pattern of growth is one of the rarest morphological variants.1 Immunohistochemical analyses play a very important role in the diagnosis of small cell malignant melanoma especially in amelanotic lesions.

Atypical carcinoid: A rare finding of a man with mediastinal mass: A case report

The present case report describes a case of mediastinal atypical carcinoid and a favorable outcome linked with the treatment. Mediastinal atypical carcinoid is a rare and aggressive type of neuroendocrine tumor. A 56-year-old man was admitted at the Respiratory Department due to intermittent tightness of the chest for 1 month. An initial diagnosis of a mass in the left anterior mediastinum was conducted using CT scan and immunohistochemistry. Laboratory data revealed the following values: Neuron Specific Enolase of 62.13 ng/ml (reference range, 0-40 ng/ml); CYFRA21 of 3.01 ng/ml (reference range, 0-3.3 ng/ml); CEA of 4.22 (0-6.5) ng/ml; SCC of 0.5 (0-1.5) ng/ml; CA125 of 67.24 (0-35) U/ml; AFP of 23 (0-25) U/ml; CRP of 96.7 (0-10) mg/l; PCT <0.05 (0-0.05) ng/ml; and ESR of 48 (0-20) mm/h. Tissue pathology revealed tumor cells with small cell pattern, and cell proliferation activity was 10%. Combined chemotherapy with bevacizumab (0.4 g, qd, once every 21 days) and capecitabine (0.15 g, Bid, Po) and timozolamine (0.34 mg, qd, po) was administered for 6 cycles. After the patient was given chemotherapy, the symptoms and CT exhibited improvement. On March 11, 2018, the lesion progressed into the lymph and pleura. The patient was commenced on radiotherapy and new chemotherapeutic regimen etoposide (0.5 g)-carboplatin (0.4 g)-bevacate (0.4 g). Another CT scan was performed after a month which revealed a substantial decrease in tumor size. Hence, a CT scan was performed for this patient who further revealed a decrease in tumor size. Currently patients are treated with bevacizumab maintenance therapy. Further studies of conservative treatment of chemotherapy and radiotherapy may provide a treatment to improve atypical carcinoid.

Localized patterns in crushed conical shells

We use experiments and numerical simulations to study the rapid buckling of thin-walled cones as they impact a solid surface at high velocities. The buildup of air pressure inside the cone localizes the deformations to the impacting interface with the solid surface, leading to the hierarchical formation of an ordered pattern of small rhomboidal cells. In contrast, when the inner air pressure is not allowed to develop, the ordered pattern is destabilized and the cone collapses in a highly disordered state on long length scales. Numerical simulations confirm that the transition between ordered and disordered crumpling is governed by the competition between the elastic deformation energy of the shells and the work required to pressurize the air. Our results show how dynamic stabilization via tensioning suppresses long wavelength subcritical instabilities in shells and leads to the localization and propagation of short wavelength patterns.

Significance of H3K27M mutation with specific histomorphological features and associated molecular alterations in pediatric high-grade glial tumors.

Pediatric high-grade gliomas (pHGGs) constitute almost 15% of all childhood brain tumors. Recurrent mutations such as H3K27M mutation in H3F3A and HIST1H3B genes encoding histone H3 and its variants were identified in approximately 30% of pediatric glioblastomas. This study aimed to ascertain the morphological and molecular characteristics of pHGGs with H3K27M mutation. In total, 61 cases of pHGGs (anaplastic astrocytoma, 12; glioblastomas, 49) from four university hospitals were studied. The histomorphological features were examined and immunohistochemistry was performed to evaluate the mutation status of H3K27M, ATRX, IDH1, BRAF V600E, and p53 genes. The study comprised 25 females and 36 males (age range, 1-18years) with a clinical follow-up of up to 108months. From the total, 31 patients were positive for H3K27M mutation located in the midline, mostly in the pons and thalamus. H3K27M mutation was commonly associated with ATRX loss (32.3%) and p53 (74.2%) immunoreactivity with a co-expression rate of 25.8%. While IDH1 mutation was not detected in pHGGs with H3K27M mutation, BRAFV600E mutation was rarely observed. Among the various histomorphological features, increased number of mitosis, increased Ki-67 proliferation index, and palisading and geographical necrosis along with small cell patterns were significantly associated with the H3K27M wild-type tumors. Focal infarct-like necrosis and pilomyxoid morphology was significantly associated with these tumors. H3K27M mutation occurs exclusively in pHGGs arising from the midline and presents with varied histomorphological features ranging from low-grade pilomyxoid astrocytoma to highly pleomorphic glioblastoma along with ATRX loss and p53 mutations.

Analysis of Cell Size in the Gastrula of Ten Frog Species Reveals a Correlation of Egg with Cell Sizes, and a Conserved Pattern of Small Cells in the Marginal Zone.

We investigated the relationship between egg and cell sizes in the early gastrula of ten species of frogs with eggs of 1,100-3,500 μm diameters. We asked whether differences in cell size of the vegetal region, blastocoel roof, and marginal zone of the early gastrula were associated with egg size. Alternatively, we proposed that cell size differences may associate with gastrulation characteristics. The analyzed species were as follows: Xenopus laevis, Engystomops randi, Engystomops coloradorum, Espadarana callistomma, Epipedobates machalilla, Epipedobates anthonyi, Epipedobates tricolor, Dendrobates auratus, Gastrotheca riobambae, and Eleutherodactylus coqui. A positive correlation between egg and cell size was detected in the three regions of the gastrula. The correlation was strong in the vegetal region and blastocoel roof, and weak in the marginal zone. Large eggs allowed the evolution of frog terrestrial reproductive modes by storing nourishment for the developing embryos. Large cells, laden with yolk, occur in the vegetal region. However, small cell size characterized the marginal zone and blastocoel roof. We proposed that small cells of the marginal zone are required for involution and blastopore formation. The evolution pressure toward small cells in the marginal zone contributed to maintain the blastopore as a universal feature of frog gastrulation in eggs of different sizes and gastrulation modes. Our comparative analysis revealed two fundamental and conserved properties of the frog early gastrula, the correlation of egg with cell sizes, and the general small size of cells in the marginal zone.

Liver pro-oncogenic potential of SERPINB3.

Hepatocellular Carcinoma (HCC) is a growing sanitary problem worldwide. This tumor is indeed the third most deadly and the fifth most common cancer all over the word, with an incidence that, at least in the United States, has doubled in the past two decades [1]. Current studies suggest that HCC can derive from liver progenitor cells or cancer stem cells (CSCs) in which signaling pathway similar to those identified in liver cancer (e.g., Wnt, TGF-β, Notch, Hedgehog, and PI3K/AKT/mTOR), are activated. These findings support the hypothesis that CSCs contribute to the molecular heterogeneity and chemoresistance of this tumor [2]. In addition, the progenitor-like subtype of hepatocellular carcinoma is associated with a poor prognosis [2]. Cancer stem cells are neoplastic cells that possess distinct survival mechanisms and stem cell properties responsible for tumor formation and progression. Although the origin of CSCs in liver cancer is not fully elucidated, has been recently demonstrated that any hepatic lineage cell (tumor progenitor cells, stem cells, or dedifferentiated cells) can be reprogrammed into CSC by activating diverse cell type-specific pathways [3]. The role of preneoplastic lesions in HCC remains still controversial. A recent study [4] has demonstrated that in foci of altered hepatocytes (FAH), consisting in highly proliferative cells, compared to the parenchyma of cirrhotic liver, resides aggregates of normal hepatocytes, oval cells and progenitor cells with high expression of specific markers, including CD90, CD44, EpCAM and alpha-fetoprotein (AFP). It was further demonstrated that this subset of cells with stem/progenitor are tumorigenic in damaged livers (i.e., in chronic injury and compensatory proliferation) and in this context the microenvironment, IL-6 and TGF-β signaling are required to promote in vivo growth and malignant progression of hepatic cancer progenitor cells and tumor metastasis [4]. In the liver, the ov-serpin SERPINB3 (or SCCA1) and its isoforms SERPINB4 (or SCCA2) are undetectable in normal hepatocytes, but their expression progressively increases in chronic liver diseases, dysplastic nodules and HCC, suggesting that they may be involved in relatively early events of hepatocarcinogenesis, although their specific role has not been defined yet [5]. In the article “SERPINB3 is associated with TGF-β1 and cytoplasmic β-catenin expression in hepatocellular carcinomas with poor prognosis” [5] Turato et al, for the first time, provided evidence that in liver tumors the expression of the protease inhibitor SERPINB3 was correlated with the molecular markers of poor prognosis, (TGF-β signalling associated with Wnt target gene expression). High expression of SERPINB3 was indeed significantly associated with early tumor recurrence, which is commonly regarded as a true metastasis, due to dissemination of primary tumor cells then representing a subset of most aggressive HCCs. These results are in agreement with previous studies in vitro, demonstrating that SERPINB3 can enhance TGF-β expression and induce epithelial-mesenchymal transition, with increased invasiveness and cell proliferation [5]. Figure 1 Proposed involvement of SERPINB3 in liver carcinogenesis The presence of SERPINB3 in human progenitor cells compartment has been recently demonstrated by our group. This serpin was indeed detected in EpCAM + cell fractions sorted from human foetal and adult livers and in the same ductular structures that express stem/progenitor cell markers. Moreover, the mouse homologous, Serpinb3b, was induced in a mouse model of liver stem/progenitor cell activation [6]. Expression of SERPINB3 protein was also observed in hepatoblastoma, considered an embryonal tumour of the liver, especially in tumors with more advanced stage. The intensity of the protein signal was higher in less differentiated components of the tumor and in the clusters of undifferentiated variant, named small undifferentiated cell (SCUD) pattern, considered as primitive uncommitted progenitor cells [7]. Recent findings revealed that SERPINB3/4 isoforms are RAS-responsive factors that can lead to inflammatory protein production and tumorigenesis. They are transcriptionally upregulated via MAPK and the ETS family transcription factors PEA3. The increased expression of these serpin family members determines NF-kB activation, essential for RAS-mediated cytokine production and tumor growth. The positive correlation between Ras mutation, enhanced SERPINB3 expression and IL-6 expression was documented in human colorectal and pancreatic tumour samples, reflecting the inflammatory and protumorigenic role of this serpin [8]. These last results, taken together with the finding that high SERPINB3 expression was detected in liver progenitor cells and in the most aggressive liver tumors [5,7] suggest that this serpin, may determine a pro-tumorogenic microenvironment milieu and cellular features with a high pro-oncogenic potential.

Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2: A paediatric case report and review of the literature

Mesenchymal chondrosarcoma is an extremely rare malignant tumour that most commonly originates in the bone, but is also present in extraskeletal sites. The tumour is morphologically characterized by a biphasic pattern of small round cells and islands of cartilage. Spinal mesenchymal chondrosarcomas are even rarer and, therefore, few investigations exist regarding the biological behaviour of the tumours. In the present study, we report a case of a 10-year-old female presenting with 9 months of back pain and radiographic findings of an intradural lesion measuring 1.5 cm at the level of Th4. The tumour was completely excised and subjected to pathological analyses. Following detection of the HEY1-NCOA2 fusion gene, the tumour was morphologically and immunohistochemically defined as an intradural mesenchymal chondrosarcoma attached to the dura mater. In this study, we validate the recent identification of the fusion gene HEY1-NCOA2 in paediatric extraskeletal mesenchymal chondrosarcomas. The relevant literature is reviewed and further discussed in relation to our findings.

Lymphohistiocytic and small cell pattern of anaplastic large cell lymphoma, ALK positive, arising in an 86‐year‐old woman

Lymphohistiocytic and small cell pattern of anaplastic large cell lymphoma, <scp>ALK</scp> positive, arising in an 86‐year‐old woman

Low-grade fibromyxoid sarcoma: an unusual cardiac location

We report the unusual cardiac localization of a primary low-grade fibromyxoid sarcoma of the right ventricle in a 57-year-old woman. Histological examination revealed a prevalent myxoid appearance with whorling growth pattern of small or spindle cells with bland features alternating with rare more collagenous hypocellular areas with rare atypical cells. Genomic polymerase chain reaction of genomic DNA revealed the typical FUS/Creb3L2 fusion gene products typical of low-grade fibromyxoid sarcoma. The tumor was surgically removed and recurred after 7 years as high-grade pleomorphic sarcoma. The patient died 6 months after the clinical manifestation of recurrence. Low-grade fibromyxoid sarcoma of soft tissues is a rare, distinctive variant of fibrosarcoma-typically arising in deep soft tissue of lower extremities and trunk-that rarely metastasizes. Clinically, low-grade fibromyxoid sarcoma is characterized by a longer survival rate compared to other sarcomas, suggesting its consideration in the differential diagnosis of cardiac tumors with a myxoid appearance.

Pitfalls in the Diagnosis of Anaplastic Large Cell Lymphoma with a Small Cell Pattern

Anaplastic large cell lymphoma with a small cell pattern is a rare T-cell lymphoma. This condition is more frequently seen in younger patients and should be considered when patients present with leucocytosis and constitutional symptoms. In this report, we describe our diagnostic work-up for one such case using blood, lymph node, and bone marrow aspirate samples, highlighting the variability of antigen expression seen in different sample types and methodologies. This case shows the importance of having a high index of suspicion and assessing CD30 and anaplastic lymphoma kinase expression in all suspected T-cell neoplasms even though this rare condition is not necessarily expected.

Small cell neuroendocrine carcinoma of the urinary bladder

Among neuroendocrine tumors of the urinary bladder, small cell carcinoma (SCCB) is the most common one. Less frequent is carcinoid tumour and very rare is a large-cell neuroendocrine carcinoma. Small cell neuroendocrine carcinoma is a very aggressive tumour, with major frequency in the seventh decade. In 95% of patients it presents with hematuria and muscle invasive disease. A case of a patient with the urinary bladder tumour, which had muscle invasion and extension in perivesical tissue, was presented. The patient was diagnosed with combined form of the tumour, consisting of small cell and squamous cell patterns. Some of the imunochistochemical markers used in diagnosis were chromogranin A, synaptophysin, cytokeratins, LCA and Ki-67. Consequently, neuroendocrine differentiation of small cell patterns of the tumour was proven. Neoadjuvant cisplatin- based chemotherapy followed by radical resection should be considered as the treatment of choice in surgically resectabile SCCB. Because of that it is essential to make histopathologic diagnosis of SCCB in transuretral tumour samples using, chromogranin A or synapthysin.

A small cell variant of ALK-positive, CD8-positive anaplastic large cell lymphoma with primary subcutaneous presentation mimicking subcutaneous panniculitis-like T-cell lymphoma

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is an uncommon non-Hodgkin's lymphoma of T-cell origin, the majority of which express CD4 and show frequent pan-T-cell antigen loss. While most cases of ALK+ ALCL have the common pattern characterized by anaplastic morphology with hallmark cells, a less common but well-recognized variant with a small cell pattern may pose a diagnostic challenge. We report a case of ALK+ ALCL with small cell morphology and CD8 subset restriction in a 53-year-old male patient who presented primarily with multiple recurrent subcutaneous nodules with histopathologic features simulating a subcutaneous panniculitis-like T-cell lymphoma (SPTCL). The case was initially diagnosed as SPTCL but was reconsidered as ALK+ ALCL when the incidental finding of CD30 positivity on a subsequent biopsy prompted an ALK immunostain, which turned out to be positive in the neoplastic T-cells. The diagnosis of ALK+ ALCL, small cell variant, was then confirmed by detection of an ALK gene rearrangement by FISH analysis. This report highlights a case of ALK+ ALCL with a deceiving clinical and histopathologic presentation, and emphasizes the value of immunohistochemical panel studies and genetic tests in such cases to avoid diagnostic errors.

A Pancreatic Mass in a Patient With Nausea and Vomiting

Question: A 71-year-old woman was admitted with intractable nausea and vomiting. The patient denied any abdominal pain but did note a 6-month history of intermittent thoracolumbar back pain. She denied any weight loss, changes to her bowel pattern, or bouts of acute pancreatitis. Her family history was notable for a sister who died of pancreatic adenocarcinoma at age 50. Physical examination revealed a palpable mass and a minimally tender abdomen to deep palpation in the epigastric region. Laboratory studies demonstrated normal electrolytes, liver function tests, complete blood count, CA 19-9, amylase and lipase levels. Abdominal and pelvic computed tomography (CT) demonstrated a 6.8 × 5.5-cm mass of the proximal pancreatic body encasing the celiac artery (Figure A). A positron emission tomography (PET) scan demonstrated FDG activity only in the pancreatic body and in a celiac lymph node (Figure B). Endoscopic ultrasonography (EUS) revealed a large, 38 × 40-mm, heterogeneous mass with areas of hypoechoic spaces compatible with necrosis arising from the pancreas (Figure C). A rounded and sharply demarcated lymph node, abutting the celiac plexus, was measured at 15 mm in diameter. What is your differential diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Cytology from the EUS fine needle aspirate (FNA) of the pancreatic mass revealed poorly differentiated malignant cells with scant, eosinophilic cytoplasm, high nuclear–cytoplasmic ratios, granular chromatin, and inconspicuous nucleoli (Figure D). A cell block was made from the FNA material and immunohistochemistry noted positive stains for AE1/AE3, TTF-1, CK7, chromogranin and synaptophysin (Figure E, synaptophysin-positive staining) but negative for CK20, CD45, CD3, and CD20, consistent with a poorly differentiated small cell carcinoma. Extrapulmonary small cell carcinoma of the pancreas (ESCCP) was diagnosed in this patient in the context of no pulmonary involvement on CT or PET scans. The patient was treated with a chemotherapeutic regimen of cisplatin and etoposide. Although a subsequent CT scan indicated an initial marked decrease in tumor size, 6 months after initial diagnosis, the patient was found to have liver metastases and subsequently passed away. ESCCP is a very rare condition, which represents approximately 1% of all pancreatic malignancies, and is frequently under-recognized, leading to a delay in diagnosis.1Galanis E. Frytak S. Lloyd R.V. Extrapulmonary small cell carcinoma.Cancer. 1997; 79: 1729-1736Crossref PubMed Scopus (245) Google Scholar Since Duguid and Kennedy first described 2 cases of a mediastinal tumor with a small cell pattern without bronchial involvement in 1930, cases of primary extrapulmonary small cell carcinoma have been described in numerous other organs.1Galanis E. Frytak S. Lloyd R.V. Extrapulmonary small cell carcinoma.Cancer. 1997; 79: 1729-1736Crossref PubMed Scopus (245) Google Scholar The pancreas is a rare site of origin for small cell carcinoma: Reyes and Wang reported only 5 histologically confirmed cases of primary pancreatic small cell carcinoma out of 485 pancreatic malignancies over a 29-year period.2Reyes C.V. Wang T. Undifferentiated small cell carcinoma of the pancreas: a report of five cases.Cancer. 1981; 47: 2500-2502Crossref PubMed Scopus (86) Google Scholar The Mayo Clinic published a case series in which out of 81 cases of extrapulmonary small cell cancer, 29 cases (36%) involved the gastrointestinal tract with only 7 cases (8.6%) involving the pancreas.1Galanis E. Frytak S. Lloyd R.V. Extrapulmonary small cell carcinoma.Cancer. 1997; 79: 1729-1736Crossref PubMed Scopus (245) Google Scholar ESCCP carries a poor prognosis, and no consensus exists on the appropriate treatment of these patients. Patients who do not undergo chemotherapy survive a median of 1 month; the median survival increases to 6 months with cisplatin-based chemotherapy.3Vos B. Awada A. Hendlisz A. Primary small-cell carcinoma of the pancreas: An extensive review of the literature with emphasis on therapy and prognosis.Cancer Ther. 2008; 6: 857-864Google Scholar ESCCP is aggressive and often widely metastatic at presentation; therefore, operative resection with curative intent is frequently not possible. In prior reports, the histologic diagnosis of ESCCP was typically made by surgical pathology after resection or post mortem by autopsy; in our case, EUS-FNA allowed for a pathologic diagnosis.

Desmoplastic Small Round Cell Tumor of Major Salivary Glands

Desmoplastic small round cell tumor is a rare malignant neoplasm mostly occurring in the vicinity of or within the peritoneal cavity, and is uncommon in the head and neck region. Tumor location within a major salivary gland is exceptional. We report a case of a 41-year-old Chinese man with a history of diabetes mellitus and end-stage renal failure on peritoneal dialysis with a desmoplastic small round cell tumor occurring in the left submandibular gland. Fine-needle aspiration cytology showed variably cohesive clusters of small cells with hyperchromatic nuclei and fine granular chromatin. On histology the neoplasm displayed classic features of a desmoplastic small round cell tumor with angulated nests of small round blue cells in a fibromyxoid/desmoplastic stroma. Neoplastic cells were immunoreactive for cytokeratins (AE1/3), desmin (paranuclear dot-like), WT-1 (nuclear), epithelial membrane antigen, and CD56. EWS gene translocation and EWS-WT1 gene fusion were detected by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, respectively. The case presented is the sixth case of and the oldest reported patient with a desmoplastic small round cell tumor occurring in a major salivary gland to date. Desmoplastic small round cell tumor should be considered in the differential diagnosis of a salivary gland neoplasm with a basaloid or small cell pattern on fine-needle aspiration cytology.

Immunophenotypic Heterogeneity of Primary Sinonasal Melanoma With Aberrant Expression of Neuroendocrine Markers and Calponin

Primary sinonasal melanoma is an aggressive tumor that often presents a diagnostic challenge owing to its rarity and variable morphology. Unusual immunophenotypic expression of sinonasal melanoma compounds the problem particularly in a limited tissue sample. We studied immunohistochemical patterns of 5 primary sinonasal melanoma using antibodies against pan-cytokeratin, S-100, HMB-45, Melan-A, chromogranin, synaptophysin, neurofilament protein, and calponin and correlated these patterns with histologic appearance. Sinus/nasal mucosa from non-neoplastic cases were stained for Melan-A to evaluate prevalence of melanocytes in the benign mucosa in comparison to the staining pattern of the mucosa adjacent to the tumor. Similar to previous report, small cell pattern appeared to be over represented in the sinonasal melanoma. Small cell population in 4 cases was almost devoid of pigment, and also was either completely negative or only focally positive for S-100. Three cases stained positive for neuroendocrine markers and neurofilament protein bringing olfactory neuroblastoma and small cell neuroendocrine carcinoma in as differential diagnosis. Three cases were focally positive for calponin without spindle cell morphology or desmoplastic reaction. Immunophenotypic heterogeneity along with the unconventional histomorphology of sinonasal melanoma compounds diagnostic problem and warrants a precautionary approach to avoid misinterpretation. It is necessary to apply a broad panel of immunohistochemistry for the purpose of screening when sinonasal melanoma is considered as a differential diagnosis.

An Ovarian Tumor With Small Cell Pattern at Intraoperative Assessment

Abstract Gynecological oncologists frequently request intraoperative assessment of ovarian or adnexal masses because the provisional pathological diagnosis is used to guide surgical management. Frozen section has been used most widely in this context, but, as in other anatomic sites, this technique has well-recognized limitations. Cytologic preparations such as scrape smears or imprints can be made easily from tumor specimens and without the requirement of expert technical assistance. They offer the potential for wider tumor sampling and optimize cellular detail without artifacts related to tissue freezing. The case presented herein illustrates the complementary value of cytologic preparations as an adjunct to diagnosis in the interpretation of an ovarian tumor exhibiting a small cell morphologic pattern.

Immunohistochemical expression of Ki67, c-erbB-2, and c-kit antigens in benign and malignant pheochromocytoma

In this study, we evaluated the immunohistochemical expression and the possible advantages of Ki67 antigen, c-erbB-2, and c-kit proto-oncogenes in the differentiation between benign and malignant pheochromocytomas. Paraffin-embedded tissue blocks from 44 benign (35 adrenal and 9 extra-adrenal) and 11 malignant (9 adrenal and 2 extra-adrenal) cases of pheochromocytoma were selected for immunohistochemical staining using antibodies against Ki67, c-erbB-2, and c-kit antigens. We investigated the relationship between the expression of these antigens and age, gender, tumor size, histologic patterns and necrosis, as well as tumor behavior. The risk of malignancy was higher when tumor size was increased. We found out that more uncommon tissue patterns, such as small cell and spindle cell patterns, are mostly indicators of malignancy. There was a statistically significant relationship between Ki67- and c-erbB-2-positive staining of the tumor cells and the malignant behavior of the pheochromocytomas ( p-value=0.000), while cytoplasmic c-kit staining did not show any correlation with tumor malignancy ( p-value=0.087). We concluded that tumor size and the histomorphologic patterns (spindle cell and small round cell) are significantly associated with tumor behavior. In addition, Ki67 positivity and c-erbB-2 expression can be used as immunohistochemical markers for predicting the malignant behavior of pheochromocytoma.