Prominent Eosinophilic Nucleoli Research Articles

ALK rearranged Spitz melanocytoma: a clinicopathological and molecular genetic analysis of two cases

Objective: To investigate the clinicopathological, immunohistochemical and molecular characteristics of cutaneous ALK-rearranged Spitz melanocytoma. Methods: Two cases of cutaneous ALK-rearranged Spitz melanocytoma from outside hospital consultations in Department of Pathology, Affiliated Cancer Hospital of Fudan University in August 2020 and in Shanghai Ackermann Medical Laboratory in June 2022 were collected. The clinicopathological features, immunophenotypes and molecular profiles of two patients with cutaneous Spitzoid melanocytic tumor harboring ALK-rearrangement were analyzed. The literatures were reviewed. Results: The study included an 8-year-old boy and an 11-year-old girl, who presented with a polypoid lesion in the skin of right thigh and left auricle measuring 1.0 cm and 1.2 cm, respectively. Histologically, they were composed of medium to large-sized epithelioid to plump spindle cells, arranged in nested, plexiform or fascicular patterns in the superficial dermis. The neoplastic cells had abundant eosinophilic cytoplasm with round to ovoid vesicular nuclei containing prominent eosinophilic nucleoli. One case showed mild to moderate nuclear pleomorphism and mitotic activity (average, 2/mm2). Immunohistochemically, the epithelioid and plump spindle cells showed diffuse and strong staining of S-100 protein, SOX10, and ALK (D5F3 and 1A4), but did not express HMB45, PNL2 and MiTF. ALK-rearrangement was detected by fuorescence in situ hybridization in both cases. Subsequent next generation sequence (NGS) analysis identified KANK1::ALK and TPM3:ALK fusions. At 34 and 14 months after surgical resection, both patients remained well with no signs of recurrence or metastasis. Conclusions: ALK-rearranged Spitz melanocytoma represents a morphologically and genetically distinct subset of Spitz melanocytoma, characterized clinically by predilection in children and adolescents, with Spitzoid morphology in plexiform pattern, positive immunohistochemical stains, and rearrangement of ALK. As some cases show atypical features and high mitotic activity, a distinction from Spitz melanoma is warranted.

Revised Diagnosis From Histiocytic Neoplasm to Optic Chiasm Glioblastoma After Genetic Analysis.

A 46-year-old man presented with left eye blurring. Automated visual field testing showed an incongruous right hemianopia, with sparing of the lower temporal quadrant in the right eye. MRI revealed foci of gadolinium enhancement in the optic chiasm and optic tracts. Serologic testing (including myelin oligodendrocyte glycoprotein and neuromyelitis optica antibodies) and cerebrospinal fluid analysis were negative. Whole-body PET/CT scan found no malignancy. Biopsy of the optic chiasm revealed a moderately cellular neoplasm composed of atypical, discohesive cells with enlarged nuclei, prominent eosinophilic nucleoli, and abundant vacuolated cytoplasm. Immunohistochemical stains for CD68 and S100 were positive, whereas those for GFAP, OLIG2, SOX10, and multiple others were negative, supporting a diagnosis of histiocytic neoplasm. Five weeks later, results became available from next-generation sequencing targeting the coding regions of hundreds of malignancy-associated genes and select introns. Alterations associated with histiocytic neoplasms (i.e. BRAF and MAP2K1 mutations) were absent. However, there was a nonsense mutation in the PTEN gene, a hotspot mutation in the TERT gene promotor, and focal amplifications of the CDK4 and MDM2 genes. Additionally, there was chromosome 6q loss, 7 gain, and 10q loss. Based on these findings, the diagnosis was revised to glioblastoma, IDH-wildtype, CNS WHO grade 4. The patient began treatment with temozolomide while continuing radiation therapy. This case illustrates how next-generation sequencing can at times provide more accurate diagnostic information than standard tissue histopathology.

Fumarate hydratase deficient uterine leiomyoma: a clinicopathological and molecular analysis of 80 cases

Objective: To investigate the clinicopathologic and molecular characteristics of fumarate hydratase (FH) deficient uterine leiomyoma. Methods: Eighty cases of FH deficient uterine leiomyoma were diagnosed from April 2018 to September 2022 in Department of Pathology, Peking University Third Hospital. Sanger sequencing of FH gene exons (exon 1-10) were performed on tumor tissues and matched non-tumor tissues/peripheral blood for all cases. FH immunohistochemistry were performed in 74 cases; S-(2-succino)-cysteine (2SC) were also detected by immunohistochemistry in five cases. Results: Patients' age ranged from 18 to 54 (36.0±7.5) years, with more than 60% exhibiting clinical symptoms of multiple and large leiomyomas (the median diameter was 70 mm). More than four histologic features, including staghorn vasculature, alveolar-pattern edema, bizarre nuclei, oval nuclei arranged in chains, prominent eosinophilic nucleoli with perinucleolar haloes and eosinophilic intracytoplasmic globules were observed in 98.5% (67/68) patients. The immunohistochemical sensitivity of FH and 2SC were 97.3% and 100%, respectively. Based on the Sanger sequencing results, the cases were divided into germline variant group (31 cases), somatic variant group (29 cases) and no variant group (20 cases). Sixty-nine percent (20/29) of the patients with FH germline variation had clear family history. Conclusions: Clinical features, histological morphology, FH and 2SC immunohistochemistry and Sanger sequencing have their own significance and limitations in differential diagnosis of FH deficient uterine leiomyoma. In clinical practice, the above information should be fully integrated and studied for accurate pathologic diagnosis and selection of patients with FH germline variation.

Metastatic malignant melanoma mimicking urinary bladder mass: A rare presentation

Introduction. Melanoma is a solid aggressive tumor characterized by the malignant transformation of melanocytes. To date, only about 35 primary and about 30 metastatic malignant melanomas of the bladder have been reported. Our objective is to report a rare case of secondary tumor of urinary bladder. Case outline. A 57-year-old man presented to the Urologic Clinic due to lower urinary tract symptoms. The urologist indicated transurethral resection (TUR). His medical history was significant for cutaneous malignant melanoma resected 3 years prior, which were localized at scapular region on the left side. Microscopic examination of the TUR specimen showed several fragments of ureter mucosa with presence of tumor and focally with normal urothel. Tumor cells were markedly atypical and polygonal in a solid pattern. The nuclei were large with variation in size and prominent eosinophilic nucleoli. Also, there were present areas with abundant brown pigment. Immunohistochemical analysis of tumor cells showed positivity for Melan A and HMB45 and negativity for GATA3. Molecular analysis showed that BRAF was mutated. Conclusion. The incidence of malignant melanoma is high and increasing, but the urinary bladder is a rare location of metastasis. However, both primary and metastatic melanomas can occur in the bladder, so the urologist and the pathologist have to consider it when it is the primary site of onset, or when it represents the first symptomatic metastasis.

Base of tongue metastasis of cutaneous malignant melanoma masquerading as a pedunculated reactive lesion. Report of a case with rhabdoid and neuroendocrine features

<h3>Objectives</h3> Metastatic melanoma (ΜΜ) represents a highly aggressive malignancy associated with poor prognosis. ΜΜ has a propensity to microscopically resemble other neoplasms by displaying diverse morphologic variations. Herein, we present a case of cutaneous melanoma metastatic to the base of tongue clinically mimicking a reactive pedunculated lesion and histopathologically exhibiting unusual rhabdoid and neuroendocrine features. <h3>Findings</h3> A 63-year old male presented for evaluation of a painless tongue mass of 5 months duration. The patient had been surgically treated for cutaneous melanoma of the right chest 5 years ago. Clinically, a pedunculated, soft, partially ulcerated, hemorrhagic mass involving the left base of tongue was noted. With a provisional diagnosis of pyogenic granuloma or other reactive lesion, an excisional biopsy was performed. Histopathologic examination revealed invasion of the connective tissue by clusters of epithelioid and/or plasmacytoid neoplastic cells with prominent eosinophilic nucleoli and various degrees of cytoplasmic melanin pigmentation. Interestingly, a small subset of cells showed rhabdoid morphology. Most tumor cells expressed Melan-A, HMB-45, SOX-10, and S-100, while cells with rhabdoid morphology were positive for Myo-D1. Chromogranin and synaptophysin were also positive in a few scattered cells. A final diagnosis of ΜΜ with rhabdoid and neuroendocrine features was rendered. Molecular investigation revealed mutations for the BRAF V600E gene, while multiple brain metastatic foci were detected on further diagnostic work-up. <h3>Conclusions</h3> Divergent differentiation of melanoma cells may cause diagnostic pitfalls necessitating thorough immunohistochemical analysis. The presence of rhabdoid cells, although infrequent in primary melanomas, is relatively common in metastatic tumors. Furthermore, neuroendocrine differentiation in melanomas is very uncommon and its co-existence with rhabdoid features is exceedingly rare. Better characterization of such histopathologic variations in melanomas with evaluation of their potential biologic significance is warranted.

Rare Case Report of Primary Gastric Melanoma

Gastric melanomas are usually metastatic, and primary is almost rare entity.&#x0D; Present case is a rare malignant melanoma of the gastric region with barely reported cases in the literature. A 65 year old male presented with pain abdomen and melena He was evaluated with relevant investigation. UGI endoscopy and PETCT shows large polypoidal irregular gastric mass in the proximal curvature extending upto gastroesophageal junction. Endoscopic biopsy a ulcero-infiltrating tumour, Individual cells are large, round, having moderately pleomorphic, hyperchromatic nuclei with prominent eosinophilic nucleoli and moderate eosinophilic cytoplasm. Immunohistochemistry of S100 and HMB45 was positive and negative for CK7 and CK20.&#x0D; Early diagnosis of primary gastric melanoma allows for better prognosis of the patient from the right intervention.

Binucleate Cells in Cytosmears: What do They Signify?

Background:Although the classic Reed-Sternberg (RS) cell is considered a diagnostic of Hodgkin's disease, RS-like cells have been noted in various benign and malignant conditions. The presence of these cells can be a diagnostic challenge.Aims:Our aim was to see if cells morphologically resembling or identical to RS cells occur in conditions other than Hodgkin lymphoma (HL) and what proportion of cases show binucleate cells in various benign and malignant conditions. We also want to discuss the diagnostic utility of cytomorphological features in predicting HL.Material and Methods:This study is a retrospective analysis of 2086 cytology cases. The cytosmears were screened for the presence of binucleate cells. A detailed cytomorphological analysis of cytosmears with binucleate cells was performed, and the diagnostic utility of cytomorphological criteria in delineating HL was examined.Results:Out of 2086 smears, 55 (2.6%) cytosmears showed binucleated RS/RS-like cells. Out of these 55 cases, 6 were HL, 3 cases were non-HL (NHL), 3 were sarcoma, 32 were carcinoma, and 11 were benign/inflammatory lesions. The presence of prominent eosinophilic nucleoli, granulomas, and eosinophils had good sensitivity and specificity in predicting the diagnosis of HL.Conclusion:A detailed cytomorphological analysis is of limited value in categorizing the RS and RS-like cells. However, few cytomorphological features such as prominent eosinophilic nucleoli, eosinophils, granulomas, and lack of clustering of atypical cells can help us in predicting HL.

Primary Extranodal Classical Hodgkin Lymphoma of the Sphenoid Sinus: A Case Report and Brief Review of the Literature

Abstract Primary sinonasal lymphoma is a relatively rare disease, particularly in Western societies, and the vast majority of these are non-Hodgkin lymphoma. Classical Hodgkin lymphoma (CHL) characteristically originates in lymph nodes; primary extranodal CHL of the sinonasal tract is extremely rare. We report a case of a 63-year-old woman with primary CHL of the sphenoid sinus. The patient presented to the emergency department with complaints of “flashing light” in both eyes. Magnetic resonance imaging studies revealed a 4.2-cm enhancing mass in the sphenoid sinus. Histologic examination of the sphenoid mass revealed a diffuse mixed inflammatory infiltrate, within which were scattered large atypical cells with enlarged nuclei with irregular nuclear contours and prominent eosinophilic nucleoli, consistent with Hodgkin/Reed-Sternberg cells. Immunohistochemical studies showed the large atypical cells to be positive for CD15 and CD30 and negative for CD20 and CD45. In situ hybridization staining for small Epstein-Barr virus–encoded RNA was also positive in the atypical cells. These findings supported the diagnosis of CHL.

Primary amelanotic melanoma of the cervix: A case report with review of literature

Primary malignant melanoma arising from the uterine cervix is extremely rare. It may be misdiagnosed, especially when amelanotic, in which case immunohistochemistry is useful in reaching the diagnosis. We present a case of 67-year-old postmenopausal patient presenting with bleeding per vaginum. Per speculum examination revealed an ulceroproliferative growth involving the cervix. Microscopic examination showed sheets of pleomorphic cells with prominent eosinophilic nucleoli and intranuclear inclusion. On histopathological examination, possibilities of poorly differentiated carcinoma and amelanotic melanoma were kept. On immunohistochemical analysis, tumor cells were strongly positive for HMB-45, S-100, and vimentin. Keeping in view the histopathological and immunohistochemical findings, diagnosis of amelanotic melanoma of cervix was given. Pertinent literature is also reviewed.

Poorly Differentiated Nonkeratinizing Squamous Cell Carcinoma of the Thymus

Thymic carcinoma represents a rare and poorly understood type of thymic epithelial neoplasm that has been the subject of much controversy. Poorly differentiated nonkeratinizing squamous cell carcinoma, also known as lymphoepithelioma-like thymic carcinoma, is a rare variant of thymic carcinoma that has not been adequately characterized in the literature. The clinicopathologic, immunohistochemical, ultrastructural, and molecular features of 25 cases are reported. The patients were 19 men and 6 women, ranging in age from 20 to 85 years (mean: 60 y). The tumors presented clinically as anterior mediastinal masses with chest pain and shortness of breath or were found incidentally on imaging studies. Tumor size ranged from 2.0 to 13.5 cm in greatest diameter. Most of the tumors were small, well-circumscribed and confined to the mediastinum. Five cases presented with large, bulky, and infiltrative masses. Histologically, the hallmark of these tumors was a neoplastic proliferation of large, round to oval cells with vesicular nuclei, prominent eosinophilic nucleoli, and scant cytoplasm. Two histologic growth patterns were identified: tumors with a heavy lymphoplasmacytic stroma (lymphoepithelioma-like pattern), and tumors showing abundant desmoplastic stroma (desmoplastic pattern). Immunohistochemical stains showed strong positivity of the tumor cells for cytokeratin AE1/AE3, CK5/6, CK18, MOC31, p16, p40, and p63. MIB-1 showed on average 35% nuclear positivity. CD117 was positive in 21/25 cases and CD5 in 20/25 cases. Epstein-Barr encoded RNA in situ hybridization was positive in only 1 case. Electron microscopy in 4 cases showed primitive round to oval cells with prominent nucleoli, scant cytoplasm and immature cell junctions. Molecular features were studied by next-generation sequencing using high quality sequence data obtained from 18 patients. Variants with allele frequency between 5% and 45% and quality scores >50 were classified as somatic. A total of 16/18 cases had one or more somatic variants of unknown significance. One case showed an IDH1 p. R132C mutation, also of unknown significance. No "actionable" genes amenable to currently available targeted therapies were identified in this cohort. Clinical follow-up was obtained in 20 patients; 14 patients were alive and well with no evidence of disease between 1.5 and 16 years after diagnosis (median survival: 4 y; mean: 5.5 y). Most survivors had relatively small tumors (<5 cm. diameter), were in stage I and II at diagnosis and showed clear surgical margins. Five patients died of their tumors with metastases to bone, brain, chest wall, lungs and lymph nodes; all were in advanced stages and showed positive margins. Prognosis for these tumors appears to be correlated with the staging and status of the margins at the time of initial surgery.

Leiomyoma With Bizarre Nuclei: Clinical and Pathologic Features of 30 Patients.

Leiomyoma with bizarre nuclei (LBN) have significant cytologic atypia, but high mitotic rate and tumor cell necrosis are absent. Although it is a benign leiomyoma variant, recurrent cases have been described. In this study, we investigated the clinical and pathologic features of LBN and compared them with related studies. A total of 30 patients diagnosed with LBN in our department were included in this study. In all cases, clinical data (age, complaint, surgery type), macroscopic features (size, location, number of leiomyomas, necrosis, and hemorrhage), microscopic features (bizarre cell distribution, bizarre cell density, cellularity, mitotic rate, tumor margin, necrosis, nuclear pseudoinclusions, karyorrhectic nuclei, prominent eosinophilic nucleoli with perinucleolar clearing, cytoplasmic eosinophilic inclusions, staghorn vessels, and alveolar-type edema), and follow-up data (recurrence and survival period) were evaluated. The mean age of the patients was 49.76 yr (range: 38-89 yr). Twenty-two patients (73%) had undergone hysterectomy and 8 patients (27%) had undergone myomectomy. The mean tumor diameter was 6.12 cm (range: 0.5-25 cm). The tumor was intramural in 11 patients (37%), subserosal in 7 patients (23%), and submucosal in 4 patients (13%). Microscopically, the bizarre cell distribution was focal in 8 patients (27%), multifocal in 12 patients (40%), and diffuse in 10 patients (33%). Bizarre cell density was low in 15 patients (50%), intermediate in 8 patients (27%), and high in 7 patients (23%). The mean mitotic count was 1.4 (0-4) in 10 high-power fields, and the tumor margin was regular in all cases. We observed pseudoinclusions in 24 of 30 (80%) tumors, karyorrhectic nuclei in 21 of 30 tumors (70%), prominent eosinophilic nucleoli with perinucleolar clearing in 12 tumors (40%), cytoplasmic eosinophilic inclusions in 11 tumors (37%), staghorn vessels in 9 tumors (30%), and alveolar-type edema in 9 tumors (30%). In addition, we examined the follow-up records of 26 patients (average duration: 58.1 mo). One patient had a smooth muscle tumor in the L3-L4 paravertebral region at 67 mo after hysterectomy. This tumor did not share similar microscopic and immunohistochemical findings to the patient's earlier uterine tumor. The definitive diagnosis of uterine smooth muscle tumors is important for the determination of the prognosis of the patient and the most appropriate therapeutic approach. As in several recent studies, our series has shown that LBN has a benign clinical course. However, other malignant morphologic criteria such as high mitotic rate and tumor cell necrosis should be excluded in the diagnosis of LBN.

Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration

AbstractHereditary leiomyomatosis and renal cell carcinoma syndrome is characterized by an increased risk of agressive renal cell carcinoma, often of type 2 papillary histology, and is caused by FH germline mutations. A prominent eosinophilic macronucleolus with a perinucleolar clear halo is distinctive of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma according to the 2012 ISUP and 2016 WHO kidney tumor classification. From an immunohistochemistry perspective, tumors are often FH-negative and S-(2-succino)-cysteine (2SC) positive. We performed a pathology review of 24 renal tumors in 23 FH mutation carriers, and compared them to 12 type 2 papillary renal cell carcinomas from FH wild-type patients. Prominent eosinophilic nucleoli with perinucleolar halos were present in almost all FH-deficient renal cell carcinomas (23/24). Unexpectedly, they were also present in 58% of type 2 papillary renal cell carcinomas from wild-type patients. Renal cell carcinoma in mutation carriers displayed a complex architecture with multiple patterns, typically papillary, tubulopapillary, and tubulocystic, but also sarcomatoid and rhabdoid. Such pattern diversity was not seen in non-carriers. FH/2SC immunohistochemistry was informative as all hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas were either FH− or 2SC+. For FH and 2SC immunohistochemistries taken separately, sensitivity of negative anti-FH immunohistochemistry was 87.5% and specificity was 100%. For positive anti-2SC immunohistochemistry, sensitivity, and specificity were 91.7% and 91.7%, respectively. All FH wild-type renal cell carcinoma were FH-positive, and all but one were 2SC-negative. In conclusion, multiplicity of architectural patterns, rhabdoid/sarcomatoid components and combined FH/2SC staining, but not prominent eosinophilic nucleoli with perinucleolar halos, differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma from type 2 papillary renal cell carcinoma with efficient FH gene. Our findings are crucial in identifying who should be referred to Cancer Genetics clinics for genetic counseling and testing.

Hodgkins Lymphoma in a Child with Sickle Cell Anaemia: A Case Report

To study the co existence of Hodgkins lymphoma in sickle cell disease in a 10-year-old boy who is also a known case of sickle cell anaemia presented to out centre with symptoms of fever, weight loss. History of previous blood transfusions was given. On clinical examination, he was found to have pallor, generalised lymphadenopathy, splenomegaly. Complete blood picture revealed haemoglobin of 9 g/dl, white blood cell count of 12,000/cu mm, platelet count of 2 lakhs. Biopsy from the cervical lymph node revealed effacement of lymph nodal architecture with replacement by scattered atypical mononuclear and binucleate Reed–Sternberg cells with moderate cytoplasm, large vesicular nucleus and prominent eosinophilic nucleoli against a background of, mixed population of small lymphocytes, plasma cells and few eosinophils. Immuno histochemistry revealed positive expression of CD15, CD30, Pax-5 in the atypical cells and thus proved to be Hodgkins lymphoma.

Leiomyoma with bizarre nuclei: a morphological, immunohistochemical and molecular analysis of 31 cases

Leiomyomas associated with hereditary leiomyomatosis and renal cell carcinoma syndrome and leiomyomas with bizarre nuclei often show overlapping morphological features, in particular cells with prominent eosinophilic nucleoli, perinucleolar halos, and eosinophilic cytoplasmic inclusions. Although hereditary leiomyomatosis and renal cell carcinoma syndrome is defined by fumarate hydratase (FH) germline mutations, resulting in S-(2-succino)-cysteine (2SC) formation, it is unknown whether leiomyomas with bizarre nuclei show similar alterations. In this study, we evaluated the morphology and FH/2SC immunoprofile of 31 leiomyomas with bizarre nuclei. DNA from tumor and normal tissues from 24 cases was subjected to massively parallel sequencing targeting 410 key cancer genes. Somatic genetic alterations were detected using state-of-the-art bioinformatics algorithms. No patient reported a personal history of renal neoplasia or cutaneous leiomyomas, but one had a family history of renal cell carcinoma while another had a family history of uterine leiomyomas. Aberrant FH/2SC expression was noted in 17 tumors (16 FH-negative/2SC-positive, 1 FH-positive/2SC-positive). On univariate analysis, staghorn vessels, eosinophilic cytoplasmic inclusions, diffuse distribution of prominent eosinophilic nucleoli with perinucleolar halos, and an ‘alveolar pattern of edema’ were associated with an abnormal immunoprofile, but only staghorn vessels remained significant on multivariate analysis. Massively parallel sequencing analysis (n=24) revealed that 13/14 tumors with aberrant FH/2SC immunoprofile harbored somatic FH somatic genetic alterations, including homozygous deletions (n=9), missense mutations coupled with loss of heterozygosity (n=3), and a splice site mutation (n=1), whereas no somatic FH mutations/deletions were found in tumors with normal immunoprofile (n=10; P<0.0001). Leiomyomas with bizarre nuclei with normal FH/2SC staining pattern more frequently harbored TP53 and/or RB1 alterations than those with aberrant FH/2SC immunoprofile (60 vs 14%; P=0.032). These data demonstrate that leiomyomas with bizarre nuclei are morphologically and genetically heterogeneous and that hereditary leiomyomatosis and renal cell carcinoma syndrome-related morphological features, abnormal FH/2SC staining, and somatic FH mutations/deletions can be seen in a subset of sporadic tumors.

An Aggressive Primary Cutaneous Follicle Center Lymphoma With c-MYC Translocation and CDKN2A (9p21) Deletion: A Case Report and Review of the Literature

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 1 female patient 85 years of age with an aggressive form of primary cutaneous B-cell lymphoma manifesting in multiple firm erythematous indurated solid nodules 1-2 cm each symmetrically on the face periorbitally and on the upper extremities bilaterally. The tumor was a de novo presentation of this aggressive form of lymphoma. The disease demonstrated an aggressive course with only transient improvement of skin lesions after chemotherapy. Punch biopsy taken from a left arm skin lesion showed a diffuse and nodular large cell lymphocytic infiltrate in the 15-20 μm range exhibiting round to oval nuclei and prominent eosinophilic nucleoli. Phenotypically, the tumor cells were CD10, Bcl-2, Bcl-6, and CD43 positive with a residuum of a follicular dendritic cell network revealed by CD21 staining. There was c-MYC rearrangement and CDKN2A deletion in this sample. The importance in reporting this case is to emphasize that in the context of primary cutaneous B-cell lymphoma, the 9p21 deletion while characteristic of the leg-type lymphoma is not a unique signature of the leg-type lymphoma and is not exclusionary to lymphomas falling under the designation of follicle center lymphoma. As with the leg-type lymphoma, however, this cytogenetic abnormality is a critical determinant to a more aggressive clinical course.

Fumarase-deficient Uterine Leiomyomas: An Immunohistochemical, Molecular Genetic, and Clinicopathologic Study of 86 Cases.

Loss-of-function germline mutations in the fumarase (FH) gene of the Krebs cycle characterize hereditary leiomyomatosis and renal cell cancer syndrome. Fumarase (FH) deficiency can be diagnosed by the loss of immunohistochemical expression. In this study, we investigated the occurrence and clinicopathologic features of FH-deficient uterine smooth muscle tumors (SMTs). A total of 1583 uterine and 157 nonuterine SMTs were examined using a polyclonal FH antibody and automated immunohistochemistry, and 86 uterine leiomyomas with an FH loss were identified. The frequencies of FH deficiency for subcohorts of uterine SMTs were 1.6% for unselected nonatypical leiomyomas, 1.8% for cellular leiomyomas, 37.3% for atypical leiomyomas, and 0% for leiomyosarcomas. One extrauterine, retroperitoneal estrogen receptor-positive leiomyoma was also FH deficient. The patient age of FH-deficient uterine leiomyomas was 20 to 52 years (median, 38 y). Grossly, these tumors were often soft and amorphous resembling a fibrothecoma. Histologically, the FH-deficient nonatypical leiomyomas lacked cellular packeting and distinct collagenous zones and showed chain-like or palisading nuclear arrangements, prominent staghorn-shaped blood vessels, oval nuclei with no or at most mild atypia, small eosinophilic nucleoli, and a low mitotic rate (0 to 1/10 HPF). The FH-deficient atypical leiomyomas had nuclear atypia often manifesting as multinucleation, prominent eosinophilic nucleoli, and mitotic activity up to 7/10 HPF, with atypical mitoses seen in 32% of cases. However, similar histologic changes were seen in some non-FH-deficient atypical leiomyomas. Loss-of-function FH-gene mutations including 5 whole-gene deletions and 3 frameshift mutations were identified in 8 of 16 FH-deficient nonatypical leiomyomas using multiplex ligation-dependent probe amplification and Sanger sequencing, respectively. Follow-up data on patients with FH-deficient atypical uterine leiomyomas revealed 19 patients alive (median follow-up 27 y) and 5 patients dead. Deaths occurred 9 to 30 years after surgery at a median age of 72 years; causes of death could not be determined. These results indicate that FH-deficient uterine leiomyomas occur with a high frequency among atypical leiomyomas and infrequently in nonatypical leiomyomas and are often histologically distinctive. They seem to have a low biological potential and lack any significant association with leiomyosarcoma.

Gastric Metastasis from Clear Cell Renal Cell Carcinoma Presenting with Gastrointestinal Bleeding: A Case Report

Introduction: Renal cell carcinoma (RCC) is the most common cancer originating from the kidney, it is responsible for 80 to 85 % of all primary renal neoplasms. The most common sites of metastasis include lungs, bones, liver, and brain. However, Gastric metastases from RCC are exceedingly. Hematogenous metastases to the stomach in general are rare with incidence in autopsy 0.2-9%. Breast cancer, malignant melanoma and lung cancer as the most common cancers metastasizing to the stomach. There are only few cases in literature of RCC gastric metastasis, most of them are of clear cell type. It can be diagnosed even many years after removal of the primary cancer which indicates slow growing potential. Case report: 67-year-old male patient with past medical history of polycystic kidney disease, live donor renal transplant in 2002, and metastatic left sided renal cell carcinoma treated with radical nephrectomy and resection of pulmonary metastasis in 2014. He presented with multiple episodes of black tarry stool for the last 2 days. He was on aspirin and ticagrelor. Initial laboratory workup showed Hemoglobin 8.8 g/dl; platelet count 344*1000/cmm; and INR 1.2. The patient was admitted for stabilization and further evaluation of gastrointestinal bleeding. The patient was started on pantoprazole infusion and ordered 2 units of PRBCs. His aspirin and ticagrelor were held. Esophagogastroduodenoscopy (EGD) showed a 2.5 to 3.0 cm polypoid mass in the gastric fundus. The polyp was 90% removed with a polypectomy snare and cautery. Bleeding occurred after the procedure and hemostasis was achieved by local epinephrine injection, and application two Cook hemostasis clips. Histologic examination demonstrates tumor composed of nests and fascicles of cells with abundant clear cytoplasm and moderately pleomorphic nuclei with prominent eosinophilic nucleoli. Immunohistochemical staining was most consistent with metastatic clear cell renal cell carcinoma, and it was comparable with right lung biopsy resected in 2014.Figure 1Conclusion: Gastric involvement in renal cell carcinoma is rare even-though it's reported. The possibility of gastrointestinal involvement should always be considered in any patient with history of cancer who presents with gastrointestinal symptoms. Immunohistochemistry is also very useful in the diagnostic workup and in many cases it is possible to make a diagnosis in the absence of access to the primary tumor.Figure 2

Cytomorphological characteristics of glassy cell carcinoma of the uterine cervix: histopathological correlation and human papillomavirus genotyping

A retrospective analysis was performed to describe the cytomorphological and histopathological findings and human papillomavirus (HPV) genotypes for glassy cell carcinoma (GCC) of the uterine cervix. Five cases of cervical GCC, in which the glassy cell features constituted at least 95% of the specimen, were included. Four patients had stage IIB GCCs and one had stage IIIB GCC. All patients underwent concurrent chemoradiation therapy. Based on pretreatment cytology, only 1 of the 5 cases was correctly diagnosed as GCC. The remaining cases were diagnosed as carcinoma of undetermined type, adenocarcinoma, poorly differentiated carcinoma, or unsatisfactory for evaluation. Cytological specimens had moderate cellularity and contained small clusters of tumor cells admixed with amphophilic, granular tumor diathesis. The tumor cells possessed large, round to oval nuclei and abundant, granular, ground-glass cytoplasm. The nuclei exhibited prominent eosinophilic nucleoli. The cytoplasm displayed sharp margins and molding, resulting in “intercellular windows” between neighboring attached cells. HPV genotyping revealed that high-risk HPV types 18, 16, and 31 were detected in 3, 1, and 1 cases, respectively. Consistent with this finding, all cases exhibited block p16 positivity, confirming the association of HPV infection with GCC. In conclusion, a distinct cytoplasmic margin, the characteristic histopathological feature of GCC, was observed in liquid-based cytological preparations. We suggest that sharp cytoplasmic outlines with molding and intercellular windows are characteristic cytomorphological features of GCC. Detection of high-risk HPV in all cases strongly supported the notion that high-risk HPV is involved in the pathogenesis of GCC.

Undifferentiated Pleomorphic Sarcoma of Larynx: A Rare Entity with Review of Literature

Sarcomas of the larynx are rare neoplasms that constitute less than 1% of laryngeal malignancies. We describe a rare case of undifferentiated pleomorphic sarcoma of larynx of a 62-year- old male who presented with hoarseness of voice. Laryngoscope showed growth over glottic region of larynx and biopsy revealed poorly differentiated carcinoma. Patient was treated with radical radiotherapy (RT). After 3 months of completion of RT, laryngoscopy and CECT revealed residual lesion. Cordectomy was done. Post- cordectomy histopathology report (HPR) and review of pre RT biopsy specimen showed tumour composed of highly pleomorphic spindle cells with moderate eosinophilic cytoplasm, vesicular nuclei with prominent eosinophilic nucleoli, frequent mitoses and occasional multinucleate cells. IHC showed tumour cells were positive for vimentin and focal positive for smooth muscle actin but were negative for Pan-CK, CK- 5/6, S-100, CD-34 and desmin. The overall features were consistent with undifferentiated pleomorphic sarcoma. Postcordectomy PET-CT showed metastatic disease. Patient was further managed with 6 cycles of Ifosfamide and Epirubicin based palliative chemotherapy (CT) and after 6 months of CT completion, patient is symptomatically better. The characteristic clinical, histopathological features and management of this rare case are described with a literature review.

A case of epithelioid blue nevus.

Although epithelioid blue nevus (EBN) is a rare variant of blue nevus that was first reported in patients with Carney complex, which encompasses cardiac and cutaneous myxomas, spotty skin pigmentation, endocrine overactivity, and psammomatous melanotic schwannomas [1], it has been also documented in the absence of such clinical features [2]. Histological characteristics of EBN are variably pigmented, large epithelioid melanocytes with vesicular nuclei and prominent eosinophilic nucleoli and a small number of melanophages that are sometimes associated with a few pigmented, spindle, and dendritic cells [3]. EBN is a diagnostically challenging entity because of its rarity and histological overlap with other pigmented melanocytic lesions, such as cellular blue nevus, malignant blue nevus, and the so-called animal-type malignant melanoma. Because it is very uncommon and no cases have been recorded in the Korean literature, this Korean case is reported.