bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Primary Tumor Site of Ampullary Carcinoma Distinct in the Setting of Morphology Subtype?
Authors: Smith C J , Scott K , Rao D
Published: November 2022

Introduction/Objective

Ampullary cancer (AC) are rare and represents only 6% of the malignant periampullary tumors. Two main histologic subtypes of AC are pancreatobiliary (Pb-AC), and intestinal (In-AC). The data on the influencing role of several characteristics associated with AC subtypes on long term outcome is still emerging. Our study aimed to analyze the two subtypes Pb-AC and In-AC regarding their primary tumor site, median overall survival, and associated precursor lesion.

Methods/Case Report

Using the cBioPortal platform and systematic bioinformatical analysis of the Cancer Genome Atlas Baylor College of Medicine Cell Reports, 2016, 133 AC patients were included and analyzed based on their morphology subtype. Of which 62 patients had the intestinal subtype, and 71 had the pancreaticobiliary morphological subtype.

Results (if a Case Study enter NA)

The role of primary tumor site was statistically significant (p-value = 0.01) among subtypes Pb-AC and In-AC (See Figure). Remarkably, the primary tumor site most associated with the pancreaticobiliary subtype was the distal bile duct, and the intestinal subtype was intra-ampullary. Additionally, the precursor lesion identification (absent vs present) was statistically significant among the subtypes (p-value = 0.01). Further, the median overall survival in ampullary carcinoma varied among the morphology of the two subtypes: In-AC (75.56 months, (95% CI: 57.04-NA)) and Pb-AC (27.04 months, (95% CI: 18.29-NA)).

Conclusion

The findings in this study highlight the complex multifactorial role of the two morphological subtypes in AC. Further studies are essential for understanding the underlying tumor site specific molecular signatures leading to subtyping and their impact on prognosis.
Temporal and Sequential Relationships Between Perianal and Severe Ileal Crohn’s, Both as Strong Representations of Crohn’s Fistulizing Phenotypes
Authors: Sivanandham S , Jakate S
Published: November 2022

Introduction/Objective

Most cases of inflammatory bowel disease can be categorized as ulcerative colitis(UC) or Crohn’s disease(CD) on the basis of clinical profile, disease distribution, imaging and endoscopic findings, and pathological abnormalities. Ileal CD with deep fissuring ulcers and imminent or overt fistulae represents a specific phenotype. A similar fistulizing phenotype is indicated by complex perianal CD which shows fistulous tracts between rectum and perineum. We followed CD patients with either disease to discover if both fistulizing phenotypes occurred concurrently or with any predictable sequence.

Methods/Case Report

From our databases, we collected 21 patients with complex perianal CD(M:F=7:14, ages 23-80) and 19 patients with fistulizing ileal CD(M:F=11:8, ages 10-67) and followed them for a period of up to 16 years(2005-2021). Our purpose was to discover if both fistulizing phenotypes occurred in the same patients, and if so, was it concurrent or in any sequence, and to find the strength of the clinical diagnosis of CD when one or both phenotypes presented in a patient.

Results (if a Case Study enter NA)

Concurrent occurrence of perianal and ileal CD was the most common(6/21 perianal & 8/19 ileal cases: total 35%). When patients first presented with perianal CD, they had an equal chance of not manifesting ileal phenotype(5/21) or manifesting it earlier(5/21: average of 5 years earlier) or later(5/21: average of 2.5 years later). However, when patients first presented with ileal CD, they had a strong possibility of having manifested perianal disease in the past(10/21 or 48%: average of 5 years), when it was overlooked as a strong indicator of Crohn’s. Perianal CD was considered a strong clinical diagnosis of Crohn’s but only when it occurred concurrently or was preceded by ileal CD. Fistulizing Ileal CD was considered a strong clinical diagnosis of Crohn’s and most cases had prior perianal CD.

Conclusion

Both perianal and severe ileal CDs are fistulizing phenotypes that are strong indicators of Crohn’s and occur concurrently in 35% of cases. When followed for a long period, both phenotypes manifest in most patients when they have severe fistulizing disease. Perianal CD appears to precede ileal CD by an average of 5 years. While fistulizing ileal CD is clinically unequivocally diagnosed as Crohn’s, perianal CD may be overlooked as Crohn’s, unless there is concurrent or prior ileal CD.
A Case of Acute Disseminated Histoplasmosis of the Liver in a Patient Receiving Amphotericin-B Therapy
Authors: Irfan A , Hamdan H
Published: November 2022

Introduction/Objective

Acute disseminated histoplasmosis (DH), caused by Histoplasma Capsulatum (HC), occurs primarily in immunocompromised hosts. It is characterized by an abrupt onset of symptoms (fever, malaise, hepatosplenomegaly, lymphadenopathy, anemia, leucopenia and thrombocytopenia) and a lack of granulomatous inflammatory response. If left untreated, death occurs within three months of the disease. The treatment of choice is a two-week course of Amphotericin-B (AmpB-Tx). Studies show a drop in fungal load in 85% of blood cultures and a drop of 1.6 U and 2.1 U in serum and urine antigen levels of histoplasmosis respectively, within 14 days of treatment thereby making it unlikely to see liver failure secondary to acute DH in a patient receiving AmpB-Tx.

Methods/Case Report

We present a case of a 41-year-old male, newly diagnosed with HIV (CD4=44; viral load=5,350,000) and DH on AmpB-Tx. At presentation, his liver function tests (LFT’s) were mildly elevated (Bilirubin =2.7mg/dL; ALP=259U/L; AST=271U/L; ALT=71U/L). On Day-9 of AmpB-Tx, he became somnolent and jaundiced with hepatosplenomegaly and ascites. His LFTs were markedly raised, showing an obstructive pattern (Bilirubin=16mg/dL; ALP=1578U/L; AST=261U/L; ALT=213U/L). On Day-11 of treatment, we received a liver biopsy for HIV cholangiopathy versus drug induced hepatotoxicity. The clinicians considered DH to be a less likely cause since the patient was already on AmpB-Tx. The liver biopsy showed hepatocytes with cholestasis, minimal acute portal inflammation and numerous portal tract and parenchymal macrophages laden with fungal organisms. Gomori-Methenamine-Silver stain confirmed the fungal organisms as being HC. This diagnosis prompted the continuation of AmpB-Tx past 14 days. The patient’s LFT’s reached maximum values of Bilirubin=18mg/dL; ALP=1680U/L; AST=355U/L; ALT=324U/L. After 25 days of AmpB-Tx, his LFT’s trended downwards with a resolution of his hepatic encephalopathy and jaundice. While a 14 day course was initially intended, AmpB-Tx was continued for a total of 28 days until a resolution of symptoms was achieved.

Results (if a Case Study enter NA)

NA.

Conclusion

Our case identifies a patient with progressive hepatic histoplasmosis in spite of AmpB-Tx. Keeping in mind and identifying such cases on pathology can alter the course of treatment for patients.
A rare case of Composite Gangliocytoma/Neuroma and Neuroendocrine Tumor (CoGNET) of the Duodenum - A case report
Authors: Omo-Ogboi A C , Thomas-Ogunniyi J O
Published: November 2022

Introduction/Objective

The unique morphologic and clinical features of neuroendocrine tumors have attracted the attention of physicians, most especially pathologists for more than a century. Neuroendocrine tumor of the duodenum is a rare entity and only accounts for ~ 2% of gastrointestinal neuroendocrine tumors. Though it was initially classified as duodenal gangliocytic paraganglioma due to the presence of sustentacular cells and its association with ganglion cells, it has now been reclassified in 2022 WHO classification as “composite gangliocytoma/neuroma and neuroendocrine tumor (CoGNET) due to its clinical features and immunophenotypic characteristics. Hence, we report a rare case of CoGNET in the duodenum.

Methods/Case Report

We present a 72-year-old female with a past medical history of hypothyroidism, hyperlipidemia, hypertension, deep vein thrombosis, and pulmonary embolism presenting with a 1-day history of abdominal pain and vomiting. Esophagogastroduodenoscopy (EGD) was performed, and it was concerning for a duodenal mass and the specimen was biopsied.

Results (if a Case Study enter NA)

The biopsy consisted of multiple tan-red hemorrhagic soft tissue, which on microscopic examination showed a triphasic histological pattern which includes neuroendocrine cells, spindle-shaped Schwannian/ sustentacular cells, and neuronal ganglion cells. Immunohistochemical stains performed showed the tumor cells are strongly positive for synaptophysin, and chromogranin; moderately positive with AE1/AE3, and patchy positive with S100. Desmin, CD117, DOG-1, CD34, and GATA were all negative in the tumor cells; the Ki-67 proliferative index was 1%. These morphological and immunophenotypic features are consistent with CoGNET.

Conclusion

CoGNET is a rare entity in the gastrointestinal tract especially in the duodenum and given its recent reclassification in 2022 WHO classification; pathologists, surgeons, and physicians need to be aware of such rare entities to improve patient care.
Subtype, Frequency, and Associated Background Histology in Males Diagnosed with Hepatocellular Adenomas: A Single Institution Study
Authors: Irri A , Fiel M I
Published: November 2022

Introduction/Objective

Hepatocellular adenomas (HCAs) are rare, benign hepatic neoplasms arising from noncirrhotic livers, most commonly diagnosed in reproductive-age women using oral contraception with female:male ratio of 10:1. These tumors are also associated with anabolic steroid use, obesity, and diabetes. HCA subtypes and their incidence in the general population are as follows: inflammatory (HCA-I) accounting for approximately 50% of cases, HNF1A- inactivated (HCA-H) in 35-40%, β-catenin-activated (HCA-B) in 10-15%, and unclassified HCA in <5-10%. We aimed to determine HCA subtype frequency in male-only cases and their associated background liver histologies.

Methods/Case Report

We performed a retrospective review of all HCAs diagnosed in males from 2000–June 2022 at Mount Sinai Hospital using keywords “hepatocellular adenomas” and “hepatic adenomas;” a total of 54 cases fulfilled the criteria. Liver biopsies and resection specimens were included; duplicate cases were eliminated, and only those cases with a definitive diagnosis of HCA were included.

Results (if a Case Study enter NA)

There were 31 patients (age range 17-73 years) included with a total number of 41 HCAs (17 from resections and 14 from biopsies). HCA-I comprised 23/31 cases (74%), HCA-H and HCA-B each encompassed 2/31 cases (6%, respectively), one HCA-I had coexistent β-catenin mutation (3%, 1/31), and one unclassified HCA had mixed HCA-I and HCA-H features (3%, 1/31). Twelve cases were diagnosed as HCA without further subtype specification (NOS) (38%). Background liver histology was available in 24 cases. Fatty liver disease (steatosis and steatohepatitis) was found in five cases, of which four were classified as HCA-I. Of seven hepatocellular carcinomas diagnosed, four arose from NOS HCAs with either unremarkable or steatohepatitis backgrounds. Three of five HCA-I showed background nonspecific chronic hepatitis while two had glycogen storage disease. The remaining ten cases had unremarkable liver backgrounds and were found involving all HCA subtypes.

Conclusion

In this cohort of male-only patients, HCA-I was the most common subtype, the frequency of which is significantly higher than is reported in the general population. Only 6% of cases were HNF1A-inactivated and β- catenin-activated, far less than the reported incidence of 35-40% and 10-15%, respectively. Additionally, our findings show that the majority of HCAs had an unremarkable liver background. Further studies are necessary to determine the neoplastic drivers among male patients that develop hepatocellular adenomas.
Jejunal Intussusception Secondary to Large Inflammatory Fibroid Polyp
Authors: Abu-Salah A , Brocken E , Mesa H , Collins K
Published: November 2022

Introduction/Objective

Inflammatory fibroid polyp (IFP) is a benign mesenchymal lesion that can arise throughout the gastrointestinal tract but are most common in the stomach, followed by the ileum and more rarely in the duodenum and jejunum. Clinical manifestations include intestinal obstruction, abdominal pain, intussusception, and bleeding. Histologically these are characterized by submucosal location, bland spindle stromal cells, abundant eosinophils and lack of lineage specific markers.

Methods/Case Report

We report the case of a 68-year-old woman with history of recurrent small bowel obstruction due to Crohn’s disease who presented with jejunal intussusception that required ileocolic resection. Gross examination revealed a 4.2 cm well-circumscribed, lobulated mass with a gray-white and fleshy cut surface. Histologic sections showed a submucosal, nodular proliferation of bland spindle cells embedded within a loose, edematous stroma associated with abundant eosinophils. No hypercellularity, necrosis, hemorrhage, or mitotic figures were identified. Immunohistochemical studies revealed that the lesional cells were positive for vimentin and negative for desmin, SMA, S100, CD1a, CD117, DOG1, ALK, Melan-A, HMB-45, CD34, and STAT6. Ki-67 proliferative index was <1%. The mass was classified as an IFP.

Results (if a Case Study enter NA)

NA

Conclusion

IFPs usually express CD34 and negative cases have been described as atypical IFPs. Activating mutations of PDGFRA appear to define this lesion molecularly and are responsible for the recruitment of eosinophils. PDGFRA mutations have been detected in both CD34 positive and negative cases suggesting they represent variants of the same entity. The putative origin of this lesion is hypothesized to be a distinct type of stromal cell: the telocyte. Surgical excision is curative for symptomatic IFP.
Two Cases of Duodenal Neuroendocrine (Carcinoid) Tumor Concurrent with Invasive Gastric Adenocarcinoma and Pancreatic Intraductal Papillary Mucinous Neoplasm
Authors: Chiu R , Yap C G
Published: November 2022

Introduction/Objective

Neuroendocrine (carcinoid) tumors of the duodenum are extremely rare and account for only 2-4% of gastrointestinal tract neuroendocrine tumors. We report two cases of incidentally discovered duodenal neuroendocrine tumor which respectively occurred in a patient with invasive gastric adenocarcinoma and in a patient with pancreatic intraductal papillary mucinous neoplasm (IPMN).

Methods/Case Report

The first case involved a 60-year old male who presented with melena and symptomatic anemia and was found on EGD to have a large circumferential mass at the gastric antrum/pylorus, which was revealed to be an invasive gastric adenocarcinoma on biopsy. At the time of distal gastrectomy for this malignancy, a concurrent, 0.6 cm-sized, low grade neuroendocrine tumor was incidentally discovered at the duodenal margin. The duodenal tumor consisted of nests and trabeculae of monotonous cells with ovoid/round nuclei, finely speckled “salt and pepper” chromatin, and low mitotic rate (< 2 mitoses/2 mm2), and invaded only into submucosa. The tumor cells were strongly and diffusely positive for neuroendocrine markers chromogranin, synaptophysin, and CD56, positive for CK7 and CDX2, negative for CK20, and with low Ki67 proliferation index (< 3%). The second case involved a 69-year old female who presented with epigastric pain and was found on abdominal CT to have a 4 cm-sized cystic mass in the pancreatic head. While biopsy of the pancreatic mass revealed an IPMN, a separate biopsy of an incidentally discovered, 1 cm-deep ulcer in the duodenum bulb revealed a low-grade neuroendocrine tumor with similar morphologic features, mitotic rate, and immunohistochemical staining pattern as the prior case while also negative for IMP3 stain. The patient had normal serum gastrin and urine HIAA levels, but elevated serum chromogranin-A levels.

Results (if a Case Study enter NA)

NA.

Conclusion

Duodenal carcinoids are rare (1-3% of primary duodenal tumors) and are mostly non-functional and unifocal. The duodenum is also the least common site (2-4%) for GI tract neuroendocrine tumors. The pathophysiology of these tumors is still poorly understood, with the majority occurring sporadically and a minority in the setting of hereditary cancer syndromes. This report documents two very rare instances of duodenal neuroendocrine tumor incidentally discovered with invasive gastric adenocarcinoma and pancreatic IPMN.
Gastrointestinal Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma with Synchronous Precancerous/Malignant Epithelial Mucosal Lesions: A Clinico-Pathologic Review
Authors: Sivanandham S , Gattuso P , Al-Sabti R
Published: November 2022

Introduction/Objective

Mucosa-associated lymphoid tissue (MALT) lymphoma of the gastrointestinal(GI) tract and synchronous precancerous/malignant epithelial lesions have been sporadically reported in literature. We sought to assess the incidence of GI MALT lymphoma and synchronous epithelial lesions.

Methods/Case Report

We performed a retrospective study by searching the pathology files at our institution from 1992 to December 2021, for GI lymphomas including extranodal marginal zone lymphoma(E-MZL).

Results (if a Case Study enter NA)

There were a total of 178 cases of lymphoma involving the GI tract. The basis of this report was formed by the 40/178(22.5%) cases, which were E-MZL. Twenty-four were males and 16 females(age range:37-80 years; mean:62 years). Sites of tumors were stomach(21), colon(6), ileum(4), duodenum(4), rectum(3), and cecum(2). Four cases were multifocal. Lymph nodes were assessed in 8/40, of which 4 were positive. One patient had malignant pleural effusion and another had retroperitoneal soft-tissue involvement. Overall, 11/40(27.5%) cases had a synchronous precancerous/malignant epithelial lesion. Gastric E-MZL were the most common (21), out of which 8(38%) were associated with synchronous epithelial lesion (3 gastric adenocarcinomas and 5 tubular adenomas(TA) at different colorectal locations). Out of 6 colonic E-MZL, 2 were associated with synchronous TAs at different colorectal sites and one rectal E-MZL was associated with cecal TA.

Conclusion

In our cohort, precancerous/malignant epithelial lesions were seen in 11/40(26.8%) of GI E-MZL cases. Gastric adenocarcinomas comprised 3/8 (37.5%) of gastric synchronous precancerous/malignant epithelial lesions; the association of E-MZL and gastric adenocarcinoma is well-known, arising in the background of chronic atrophic gastritis and intestinal metaplasia secondary to chronic inflammatory disorders. The remaining 8 cases of synchronous mucosal epithelial lesions were TAs at different colorectal sites. Based on our observations, unlike gastric adenocarcinoma, the association of colorectal pre-cancerous lesions with E-MZL is less likely, since, in all cases, the TAs were seen in sites other than E-ZML sites and also, sporadic colorectal TAs are a common pathology. However, possible association between E-MZL and precancerous mucosal epithelial lesions needs more work and further investigation.
An Interesting Case of Acute Colitis Possibly Associated with Deposition of Pharmaceutical Fillers
Authors: Rahmanov N , Varshney N , Chakraborty J
Published: November 2022

Introduction/Objective

Crospovidone and microcrystalline cellulose, known as pharmaceutical fillers, are nonabsorbable and insoluble white powders. They are widely used in the pharmaceutical and food industries to facilitate the delivery of consumed substances and can be identified in pathological specimens from the gastrointestinal tract. Here, we report a case of diarrhea and colonic inflammation associated with extensive deposition of crospovidone and microcrystalline cellulose within the colonic mucosa.

Methods/Case Report

A 49-year-old male with no significant past medical history presented with abdominal pain and diarrhea for 3 weeks. CT abdomen showed wall thickening and inflammatory stranding throughout the colon, and area with possible pneumatosis coli versus pseudo-pneumatosis. Colonoscopy revealed segmental involvement with congested, erythematous and friable mucosa confined to hepatic flexure, transverse colon and splenic flexure. The biopsies of these areas showed colonic mucosa with chronic and acute inflammation, architectural distortion of the glands, melanosis coli, and extensive deposition of foreign body material within the mucosa. Closer microscopic examination of the foreign body material revealed an aggregate of coral-shaped particles with a pink center and purple periphery, which were non-birefringent under polarized light, consistent with crospovidone. Also, there was an extensive deposition of aggregates of polygonal, transparent fragments which appeared brightly birefringent under polarized light, consistent with microcrystalline cellulose. The patient denied the usage of laxatives.

Results (if a Case Study enter NA)

NA.

Conclusion

Although the data does not suggest an association between the presence of pharmaceutical fillers within the gastrointestinal tract and mucosal injury, our case suggests the possibility of associated colitis. Here, extensive mucosal deposition of crospovidone and microcrystalline cellulose shows possible association with endoscopic findings of congested and inflamed colonic mucosa, supported by microscopic examination of the sampled tissue. Hence, more investigation of iatrogenic foreign body materials, such as pharmaceutical fillers is required for optimal patient care.
Synchronous Bilateral Testicular Tumors with Different Histology: Case Report and Review of Literature
Authors: Khalaf Z , Irfan A , Mateescu V
Published: November 2022

Introduction/Objective

Germ cell tumor (GCT) is the most common cancer among males in the 20–39 year-old age range, representing 21% of invasive cancer diagnoses. Majority of bilateral testicular tumors are metachronous. The synchronous tumors comprise approximately 0.5%-1% of all cases. Most of the synchronous tumors share the same histologic pattern, predominantly seminoma. The synchronous bilateral testicular GCTs (SBTGCTs) with discordant subtypes are extremely rare.

Methods/Case Report

A 26-year-old male presented with left testicular pain, the ultrasound revealed bilateral testicular masses with calcifications and microlithiasis in the right side. His serum markers showed elevated alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG). Lactate dehydrogenase (LDH) was normal. He underwent bilateral orchiectomy. The pathology report showed a non-seminomatous mixed germ cell tumor, 2.0 cm in greatest dimension, predominantly embryonal carcinoma (90%), with a minor yolk sac tumor component (10%), lymphovascular invasion, Germ-cell neoplasia in situ (GCNIS) and calcifications in the left testicle, and a seminoma, 0.3 cm in greatest dimension with GCNIS and calcifications in the right testicle. The pathologic staging was pT2pNX for the left testicle and pT1pNX for the right testicle. Computed tomography (CT) revealed two mildly enlarged left sided para-aortic retroperitoneal lymph nodes. Radical pelvic lymph node dissection was performed. The pathology report showed four para-aortic lymph nodes positive for metastatic carcinoma. Tumor was positive for CD30 in the embryonal component, positive for Glypican-3 in the yolk sac tumor component, and seminoma was positive for PLAP. The final staging was IIB for the left testicle and IA for the right testicle. He underwent 4 cycles of Etoposide and Cisplatin chemotherapy (EP). He is in complete remission after 10 months of his diagnosis.

Results (if a Case Study enter NA)

NA.

Conclusion

The SBTGCTs with discordant subtypes represent a rare entity with no standard therapy. Our patient was treated with 4 cycles of chemotherapy and achieved complete remission.
A Rare Case of Paratesticular Cystadenoma with Ovarian Stroma Found by Scrotal Ultrasound on a Cirrhotic Patient with Elevated Alpha-fetoprotein
Authors: Fujita Y , Ittmann M M , Rosen D G
Published: November 2022

Introduction/Objective

Paratesticular cystadenoma with ovarian stroma is a rare benign cyst-forming neoplasm with less than 10 cases reported in the literature. Typically, it presents in men aged 11 to 68 years (average 30) and is asymptomatic. The tumor is hypothesized to represent the efferent ductulus undergoing metaplastic change, the vestigial remnants of Mullerian duct, or mesothelium of the tunica vaginalis. Most tumors are considered benign, but a few cases of malignant transformation have been reported.

Methods/Case Report

We present a case of a 54-year-old male with a history of cirrhosis and elevated alpha-fetoprotein (17.85 ng/ML) who was found to have a paratesticular mass by scrotal ultrasound. Clinical history was obtained from review of electronic medical record. CD10 (Novocastra Clone 56C6) and progesterone receptor (PR) (Leica Clone 16) Immunoperoxidase stains were performed following the vendor recommendations. Surgical excision revealed a 0.6-cm polypoid nodule on tunica albuginea that was entirely submitted. Microscopically, the tumor was comprised of cystic spaces lined by cuboidal epithelium identical to that of the Fallopian tubes. There was a sparse spindle-shaped stroma underlying the epithelium similar to ovarian stroma. No nuclear atypia or mitosis was found. Immunoperoxidase stains showed the epithelium was positive for PR, and the stroma was positive for CD10. No evidence of germ cell tumor was identified.

Results (if a Case Study enter NA)

NA.

Conclusion

Characteristic histologic and immunophenotypic findings can aid in the diagnosis of paratesticular cystadenoma with ovarian stroma. Surgical resection for histological confirmation and long-term monitoring for the potential recurrence and metastatic spread are required.
Primary Carcinoid Tumor of the Prostatic Urethra: Case Report and Review of the Literature
Authors: Potterveld S K , Olson D
Published: November 2022

Introduction/Objective

We report a case of a 72-year-old male with a past medical history of previously treated urothelial cell carcinoma without recurrence in over ten years.

Methods/Case Report

Surveillance cystoscopy revealed a small lesion involving the prostatic urethra. Microscopic examination of the prostatic urethra lesion revealed a proliferation of pseudoglandular structures within the lamina propria adjacent to an area of urothelial cystitis cystica et glandularis. The pseudoglandular structures contained primarily small bland nuclei with fine chromatin and featured frequent intracytoplasmic neuroendocrine granules. Scattered foci of enlarged hyperchromatic nuclei were present, but no necrosis or increased mitotic activity was identified. Immunohistochemistry revealed the lesional cells were diffusely positive for chromogranin and synaptophysin; while negative for GATA3 and NKX3.1. The histologic features and immunoprofile are characteristic of primary carcinoid tumor of the prostatic urethra, which uniquely shows a predominantly pseudoglandular architecture compared to carcinoid tumors of other sites and are often associated with reactive urothelial proliferations.

Results (if a Case Study enter NA)

NA.

Conclusion

Acknowledgement of this rare entity as a diagnostic mimicker is critical to ensure proper treatment and management of the patient.
An Extremely Rare Case of Renal Collision Tumor Comprised of Hyperpigmented Microcystic Chromophobe Renal Cell Carcinoma and Papillary Renal Cell Carcinoma
Authors: Sun Y , Takeda K , Sutton A , Geradts J
Published: November 2022

Introduction/Objective

Renal collision tumors are rare lesions defined as the coexistence of two adjacent but histologically distinct tumors with sharp borders forming a single lesion. A combination of chromophobe renal cell carcinoma (ChRCC) and papillary renal cell carcinoma (RCC) is extremely rare. Here we report a collision tumor of hyperpigmented microcystic ChRCC, an uncommon variant of ChRCC, and papillary RCC. To our knowledge, it is the first reported case of this particular combination.

Methods/Case Report

A 70-year-old male with aortic stenosis presented with dyspnea and renal insufficiency. A renal mass was discovered incidentally. MRI characterized the left renal mass as 7.2 cm and bilobed. Radical nephrectomy was performed. Grossly, the tumor was located in the upper pole and consisted of two distinct components separated by fibrous tissue: a 5.4 cm black/orange mottled tumor and an adjacent 5.0 cm yellow lobulated tumor. Histologically, the larger tumor displayed a microcystic and solid pattern comprised of large cells with pale cytoplasm, hyperchromatic wrinkled nuclei, perinuclear halos, prominent cell membranes, and extensive intracellular and extracellular brown-black pigment, consistent with hyperpigmented microcystic ChRCC. The adjacent tumor showed diagnostic features of papillary RCC including papillae with fibrovascular cores lined by columnar cells with low nuclear grade, abundant macrophages, and foci of psammomatous calcifications. The hyperpigmented microcystic ChRCC was positive for CD117 and negative for Melan-A. Papillary RCC was strongly positive for Cytokeratin7 and Vimentin.

Results (if a Case Study enter NA)

N/A

Conclusion

Meticulous examination of the histologic features, aided by immunohistochemistry, can generate an accurate diagnosis of collision tumor and direct to the appropriate treatment choice.
P63-expressing Prostate Adenocarcinoma: A Case Study of a Rare Subtype
Authors: Harbert J , Chen J , Dewenter T , Bhalla R , Halat S K
Published: November 2022

Introduction/Objective

Prostate acinar adenocarcinoma (PCa) is a well-researched,and often diagnosed entity. A combination of architectural and cytologic characteristics are used in accurately identifying these carcinomas. However, the diagnosis can be challenging when the foci are minute or the cancer presents with unusual features. Ancillary studies aid in these scenarios. The loss of basal cells in adenocarcinoma makes markers targeting these cells desirable. PIN4 cocktail immunohistochemical stain, which combines alpha-methylacyl-coA racemase (AMACR), that is overexpressed in prostate carcinoma, with basal markers high molecular weight cytokeratin and p63, is a popular ancillary study to assist diagnosing demanding cases. Herein, we present a rare, challenging subtype of prostate carcinoma expressing p63.

Methods/Case Report

A 66-year-old male, with a past medical history of treated HIV and hyperlipidemia, underwent screening biopsies for a PSA of 7.5 ng/mL. Out of 22 parts, three cores showed modest amounts of atypical infiltrating cells. The architecture comprised of ill-defined glands, individual cells and single files of cells. They possessed high nucleocytoplasmic ratio giving a hint of atrophy, with occasional spindling and prominent nucleoli. To add to the challenge, PIN4 immunostaining showed strong nuclear expression of a basal marker with negative AMACR. Due to unusual morphology and basal marker expression, a consideration of basal cell lesion was entertained. However, subsequent staining revealed negative expression of HMWCK, and positive expressions of NKX3.1 and p40. Overall, with this morphology and immunoprofile we diagnosed our case as prostate carcinoma with aberrant expression of p63.

Results (if a Case Study enter NA)

N/A

Conclusion

Grading these lesions is controversial as they are considered to carry a better prognosis over conventional acinar adenocarcinoma of similar grade. A distinct etiopathology is suspected as molecular tests for ERG and PTEN are without alterations. Further discussion and characterization of these lesions is warranted as they are infrequently encountered and prone to being overlooked due to their similarities to benign basal cells.
Incidental Succinate Dehydrogenase (SDH) Deficient Renal Cell Carcinoma and Paraganglioma in a 24-Year-Old
Authors: Freeman J , MONIKA F , Didde R D , Siref L , Alouch N
Published: November 2022

Introduction/Objective

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is rare neoplasm (<0.2% of all RCCs) caused by SDH-subunit gene mutation, usually SDHB. Patients carrying such mutations are also predisposed to other SDH-deficient neoplasms such as paraganglioma, gastrointestinal stromal tumor, and pituitary adenoma. Here, we report a case of incidental SDH-deficient RCC and paraganglioma.

Methods/Case Report

A 24-year-old male without past medical or family history presented to ED for perianal abscess. Imaging showed 8-cm heterogeneous left renal mass (figure-A) and 3.3-cm mass below aortic bifurcation, highly concerning for RCC with metastasis. Biopsy of kidney mass showed nested and trabecular epithelial neoplasm with weakly eosinophilic and occasionally vacuolated cytoplasm (figure-B). Nuclei were round with smooth contour and inconspicuous nucleoli. Tumor was immunopositive for PAX8, e-cadherin, P504S, and CD10, while negative for CK7, CD117, and Melan-A. SDHB immunostain was negative in tumor with intact staining in intervening endothelium. Findings were consistent with SDH-deficient RCC. Biopsy of pelvic mass showed low-grade neoplasm that was immunopositive for synaptophysin, chromogranin, and GATA3, with S100-positive sustentacular cells, consistent with paraganglioma. Patient underwent radical nephrectomy which revealed 7.5-cm, well-circumscribed, tan-red, predominantly solid mass with few cysts. Histologically, tumor had thin fibrous capsule and morphologically similar to biopsy. Tumor was limited to kidney without necrosis, sarcomatoid/rhabdoid differentiation, or vascular invasion.

Results (if a Case Study enter NA)

NA.

Conclusion

SDH-deficient RCC is rare low-grade entity with risk of metastasis and development of other neoplasms, which requires continued follow-up and potential genetic testing for patient and family members. Therefore, including SDH-deficient RCC in differential diagnosis of eosinophilic renal neoplasms is essential.
Cadherin-16 (CDH16) Immunohistochemistry: A Novel Diagnostic Tool for Renal Cell Carcinoma and Papillary Carcinomas of the Thyroid
Authors: Lennartz M , Minner S , Gorbokon N , Menz A , Krech T , Höflmayer D , Simon R , Blessin N C , Sauter G , Clauditz T S , Hinsch A
Published: November 2022

Introduction/Objective

Introduction: Cadherin-16 (CDH16), also termed kidney specific cadherin (ksp-cadherin), is a membrane-associated glycoprotein with a role in the embryonal development of tubules in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid.

Methods/Case Report

Methods: A set of tissue microarrays containing 14,978 samples from 149 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry to determine the expression of CDH16 in cancer and to assess the diagnostic utility of immunohistochemical CDH16 analysis.

Results (if a Case Study enter NA)

Results: Among normal tissues, a membranous CDH16 immunostaining predominated in thyroid, kidney, cauda epididymis, and in mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 83% of follicular adenomas, 58% of follicular carcinomas, but in only 9% of papillary carcinomas (p<0.0001). Among non-thyroidal tumors, CDH16 positivity was particularly frequent in nephrogenic adenomas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), clear cell (56%), mucinous (36%), and endometroid (16%) carcinomas as well as carcinosarcomas (18%) of the ovary, adenocarcinomas of the cervix uteri (40%), serous (33%), clear cell (33%), and endometroid carcinomas (18%) of the endometrium and in various subtypes of neuroendocrine neoplasms (4-26%).

Conclusion

Given the massive loss of CDH16 expression in >90% of papillary carcinomas of the thyroid, CDH16 is a highly useful diagnostic marker for these tumors. CDH16 immunohistochemistry is also useful for the identification of nephrogenic adenomas and the distinction of renal cell carcinomas from other neoplasms.
Multifocal Malignant Epithelioid Mesothelioma of the Testis
Authors: Karimi S S , Alagiozian-Angelova V
Published: November 2022

Introduction/Objective

Testicular mesothelioma is an extremely uncommon entity, and presents with non-specific clinical symptomatology, including painless scrotal enlargement and hydrocele formation. Testicular mesothelioma arising from the mesothelial cells of the tunica vaginalis accounts for 0.3%-5% of all mesothelioma cases and is often associated with poor prognosis. While the pathophysiology of this entity remains unclear, exposure to asbestos and long-standing hydrocele are associated risk factors.

Methods/Case Report

Herein, we present a case of a 65-year-old male with history of hypertension, 4-year history of left scrotal hydrocele, and a 7-month history of painless, progressively enlarging left scrotum. Scrotal ultrasound revealed a left, septated hydrocele with multiple heterogenous intratesticular masses. A left radical orchiectomy was performed and the specimen was sent to pathology for histopathological evaluation. Gross examination revealed a tan-brown fluid-filled cystic and solid mass measuring 7.5 x 4.0 x 3.5 cm involving the entire epididymis with multiple pink-tan, friable, papillary excrescences and nodules in the intratesticular parenchyma. Microscopic examination revealed a cystic and solid lesion with tubular and papillary architecture comprised of cuboidal cells with cellular pleomorphism, irregular nuclear contour, and dense chromatin involving the epididymis, rete testis, tunica albuginea, the testicular parenchyma including the hilar fat and the spermatic cord stroma. Immunohistochemical staining of the lesion demonstrated positive staining with AE1/AE3, CK7, WT1, PAX8, Calretinin, Vimentin, Podoplanin D2-40, and lack of staining with Chromogranin, Inhibin, MART-1, SMA, AFP, CD99, S100, c-kit, PLAP, HCG, MOC31, BerEP4. Based on the histomorphology and the immunophenotype of the lesion, a diagnosis of an epithelioid-type malignant mesothelioma was favored.

Results (if a Case Study enter NA)

N/A.

Conclusion

Malignant epithelioid mesothelioma of the testis is a rare and important clinical consideration for patients presenting with scrotal lesion, non-specific clinical presentation, and a history of asbestos exposure and/or long- standing hydrocele.
Automated Prostate Cancer Identification Facilitates Prognosis Marker Assessment in 11,845 Prostate Cancers Using Artificial Intelligence and BLEACH&STAIN Multiplex Fluorescence Immunohistochemistry
Authors: Blessin N C , Müller J , Mandelkow T , Bady E , Lurati M C , Lennartz M , Graefen M , Sauter G , Steurer S
Published: November 2022

Introduction/Objective

Although most prostate cancers behave in an indolent manner, a small proportion is highly aggressive. To evaluate the patient’s risk, several prognosis parameters, that can be accompanied by a high interobserver variability has been established. A reproducible prognostic evaluation is lacking.

Methods/Case Report

To enable automated prognosis marker quantification, we have developed and validated a framework for automated prostate cancer detection that comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of BLEACH&STAIN multiplex fluorescence immunohistochemistry (mfIHC). We have used the analysis framework to measure PSA, PSMA, INSM1, AR, Ki-67, CD56, Chromogranin A, Synaptophysin, CD8 in a cohort of 11,845 prostate cancers.

Results (if a Case Study enter NA)

The Ki-67 labeling index provided the strongest prognostic information among all analyzed prognosis marker in 11,845 successfully analyzed prostate cancers (p<0.001 each). The combined analysis of the Ki67-LI and Gleason grades obtained on identical tissue spots showed that the Ki67-LI added significant additional prognostic information in case of classical ISUP grades (AUC:0.82 [p=0.002]) and quantitative Gleason grades (AUC:0.83 [p=0.018]). Several combinations of these 8 prognosis markers were combined to prognosis scores and used for unsupervised clustering to identify a proportion of prostate cancers with a particularly poor prognosis (p<0.001 each).

Conclusion

Automated prostate cancer identification enables fully automated prognosis marker assessment in routine clinical practice using deep learning and BLEACH&STAIN mfIHC.
Personalized Liquid Biopsy May Predict Relapse in Aggressive Endometrial Cancer
Authors: Harris F , McCune A , Murphy S , Smadbeck J , Ali M , Penheiter A , Karagouga G , Sadeghian D , Cucinella G , Mariani A , Vasmatzis G
Published: November 2022

Introduction/Objective

High-grade endometrial cancer (EC) recurs in 50% of patients following surgery and first-line chemotherapy. There are no established blood-based biomarkers with sufficient specificity and sensitivity to monitor EC patients for residual disease and recurrence. The ability to detect and monitor EC currently relies on serial imaging based approaches. Liquid biopsies via blood-based tests for cell-free circulating tumor DNA (ctDNA) are becoming increasingly popular, but none have been FDA approved for EC and current approaches have not been validated in patients with uncommon tumor mutations. We hypothesized that personalized testing panels based on tumor-specific chromosomal rearrangements would allow ctDNA to be monitored and that ctDNA presence correlates with other clinical indicators of recurrence.

Methods/Case Report

Twelve patients with FIGO Stage I-IV and biopsy confirmed high-grade EC were prospectively enrolled and underwent primary tumor resection. DNA was isolated from tumor tissue and sequenced on Illumina NGS platforms [San Diego, CA]. BIMA algorithm and SVAtools identified junctions of somatic chromosomal rearrangements and 4-5 junctions were chosen per patient, based primarily on copy number/amplification level. Blood was collected before surgery, and longitudinally between 1 and 7 timepoints. Total cell-free DNA (cfDNA) was extracted from platelet poor plasma with the Qiagen CNA kit [Germany]. Personalized ctDNA qPCR Taqman [IDT, Coralville, Iowa] probe assays were developed with pooled pre-amplification to maximize sensitivity for the multiple junctions and normalized to input.

Results (if a Case Study enter NA)

ctDNA was detected in 9/12 and 5/12 cases pre- and post-surgery, respectively. The detection or absence of measurable ctDNA following surgery showed high correlation with cancer recurrence as detected by CT or MRI scans.

Conclusion

The detection of ctDNA in high-grade EC using personalized junction panels shows promise for a blood-based assay that may help physicians better monitor and treat patients.
Vulvar Perivascular Epithelioid Cell Tumor: A Case Report of a Rare Neoplasm in an Uncommon Site
Authors: Alassfar M , Rayes-Danan R , Hammad A , Abramovich C , Ganesan S
Published: November 2022

Introduction/Objective

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms that arise in a variety of soft tissue and visceral sites. In the female genital tract, PEComas arise in the uterine corpus and are rarely identified outside the uterus, with only a few cases reported in the vulva in the English literature.

Methods/Case Report

We report a case of a 75-year-old African American female, with a history of smoking and type II diabetes, who presented with a painless and mobile introital mass (2.5 cm). Incision and drainage were done, and a curettage sample was submitted for surgical pathology. Histologic features of the lesion revealed nests of epithelioid tumor cells with eosinophilic cytoplasm, round to oval nuclei and prominent nucleoli, in addition to thin-walled capillary vessels between nests of tumor cells. Immunohistochemical stains showed the tumor cells were positive for smooth muscle actin, MiTF, cathepsin-K, and focal MSA. Melan-A showed focal patchy staining. SMARCA4 and INI1 showed normal/retained nuclear staining. The tumor cells were negative for TFE3, vimentin, PAX8, p63, keratin, CK7, CK20, EMA, CK5, desmin, myoglobin, CD45, CD68, CD138, CD163, GATA3, chromogranin, synaptophysin, INSM1, S100 protein, HMB45, SOX10, inhibin, calretinin, CD31, and CD34. The tumor was morphologically and immunophenotypically consistent with PEComa. Complete excision of the lesion showed a 1.2 x 1.0 x 0.6 cm well circumscribed lesion, with no infiltrative borders and clear margins. The morphologic features of the tumor, including the relatively small size with absence of tumor necrosis, vascular invasion, and high mitotic activity favor a benign nature of this PEComa and suggest a low risk of recurrence. Therefore, no additional treatment was indicated.

Results (if a Case Study enter NA)

NA

Conclusion

PEComas are uncommon mesenchymal neoplasms that arise from distinctive perivascular epithelioid cells, typically arranged around blood vessels and usually express combined myomelanocytic immunophenotype. There are only a few reported cases of PEComas in the vulva. Malignant neoplasms tend to be ≥ 5cm and illustrate nuclear atypia, marked pleomorphism, conspicuous mitoses, vascular invasion and infiltrative margins. Based on the gross and microscopic features, the tumor in our case is likely to behave in a benign fashion; however, more studies are needed to further understand the behavior and the pathophysiology of vulvar PEComas.
Case report: carcinosarcoma of the fallopian tube
Authors: Sun Y , Takeda K , Stalls J , Sutton A , Chen S
Published: November 2022

Introduction/Objective

Carcinosarcoma is a malignant biphasic tumor composed of carcinomatous and sarcomatous elements. Carcinosarcoma of the fallopian tube is an extremely rare malignancy with fewer than 100 cases reported in the literature. We report a rare case of carcinosarcoma arising from the right fallopian tube.

Methods/Case Report

A 72-year-old female presented with worsening vaginal discharge and abdominal cramps.

Abdominal computed tomography detected a right adnexal mass. A torsed fallopian tube with a large mass was identified intraoperatively. Grossly, a 3.1 cm tan friable mass was seen protruding from the right fallopian tube lumen with numerous detached tumor fragments (9.4 cm in aggregate). Microscopically, the tumor was biphasic with a major mesenchymal component and minor epithelial component. A solid pattern of spindled and epithelioid cells with heterologous element of chondrosarcoma and a separate component with features of high-grade serous carcinoma in cribriform and solid sheets with slit-like spaces were seen. Both components showed marked nuclear atypia, pleomorphism, prominent nucleoli, and frequent mitoses. Both components were positive for p53, PAX-8, and beta- catenin immunohistochemistry, with a Ki-67 index of 80-90%. The sarcoma component was positive for p16, vimentin, and smooth muscle actin; the carcinoma component was positive for WT1, pan-cytokeratin, and cytokeratin 7. Pelvic washings were negative for malignancy. Metastases were not identified. Chemotherapy with paclitaxel and carboplatin was initiated with no recurrence identified 17 months after treatment.

Results (if a Case Study enter NA)

N/A

Conclusion

Proper identification and reporting of rare malignancies, such as this fallopian tube carcinosarcoma, with treatment and follow up, provide oncologists with the necessary information to advance treatment.