Can EUS-FNA cytology reliably classify gastric submucosal spindle cell tumors?

BACKGROUND: Cytological diagnosis using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for gastric submucosal spindle cell tumors, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas, is challenging because of their similar morphological characteristics. OBJECTIVE AND MATERIALS: To clarify the cytological differential points, we reviewed the EUS-FNA cytology specimens of GISTs (37 cases), leiomyomas (11 cases), and schwannomas (4 cases). METHOD: Twelve cytomorphological features were evaluated: lymphocytes, crushed nuclei, naked spindle nuclei, mast cell, length of the streaming arrangement, cellularity, nuclei at the cluster margin (nuclei located at the periphery of the cell cluster), peripheral feathering (loosely aggregated cells at the margin of a cell cluster tended to taper like feathers), metachromasia, wavy nuclei, fishhook-type nuclei, and anisonucleosis. RESULTS: Among these features, lymphocytes, naked spindle nuclei, length of the streaming arrangement, cellularity, nuclei at the cluster margins, peripheral feathering, and anisonucleosis were statistically significant for differentiation. Based on these findings, we developed an algorithm for cytodiagnosis. The algorithm was taught to four cytologists, and the interobserver agreement and correct diagnosis rates were compared before and after education, which showed a significant improvement. DISCUSSION: The histological types of gastric submucosal spindle cell tumors can be estimated using this algorithm for EUS-FNA cytology. Furthermore, this algorithm can be applied for cytological diagnosis at bedside during rapid on-site evaluation.

Gastric-type duodenal neoplasms with rapid growth: A report of two cases.

While duodenal neoplasms of the gastric phenotype are uncommon and their natural history is unknown, gastric neoplasms of gastric phenotype reportedly grow rapidly and can invade the submucosa. Several studies suggest that duodenal neoplasms of gastric phenotype might have a high risk of deep invasion and lymph node metastasis. Duodenal neoplasms of gastric phenotype might also have a high biological malignancy and likely require early treatment if detected. Here, we report two cases of intramucosal duodenal carcinoma with a gastric phenotype that grew rapidly but was successfully resected endoscopically.

Impact of Neoadjuvant Chemotherapy on SATB2 Expression in Colorectal Carcinomas: SATB2 Positivity is Preserved in Most Cases, but Down-Expressed in Effective Cases of Chemotherapy.

Special AT-rich sequence-binding protein 2 (SATB2) is a novel, diagnostically useful, and highly sensitive immunohistochemical marker for both primary and metastatic colorectal or appendiceal tumors. In the present study, we aimed to assess the impact of neoadjuvant chemotherapy on SATB2 expression in primary colorectal carcinomas and their corresponding liver metastases. Forty-four patients with colorectal carcinomas who received neoadjuvant chemotherapy were included. SATB2 expression in specimens of biopsy, resected primary colorectal carcinomas, and resected metastatic foci were examined by immunohistochemistry and compared to caudal-type homeobox transcription factor 2 (CDX2). Using a modified H-score, expressions were scored semiquantitatively for both staining intensity and tumor cell proportion with nuclear staining. SATB2 was positive in 43/44 cases (98%) in biopsy specimens, 42/44 cases (96%) in resected colorectal carcinomas with neoadjuvant chemotherapy, and 9/9 cases (100%) with liver metastases. However, these expressions were variably decreased, and the H-score was lower in resected colorectal carcinomas (158 ± 69) than in biopsy specimens (174 ± 60) (p < 0.01). The proportion of SATB2-positive area of colorectal carcinoma was 93% in metastatic foci, while the CDX2-positive area was 78%. When categorized by histopathological tumor regression, the most effective tumors of chemotherapy showed the lowest H-score in resected colorectal carcinomas among the three groups (p < 0.01). SATB2 is a useful marker for both primary colorectal carcinoma and corresponding liver metastases, even with neoadjuvant chemotherapy. However, caution should be exercised when performing needle biopsy for metastatic foci with neoadjuvant therapy because expressions could be decreased, especially in chemotherapy-effective cases, and show immunohistochemically negative results.

[Transformation of follicular lymphoma to classical Hodgkin lymphoma during observation].

A 44-year-old female was diagnosed with follicular lymphoma (FL), grade 3A stage III, by right cervical lymph node biopsy at the age of 43 years. The patient chose to not receive the treatment despite the high tumor burden. The patient came back after 18 months with respiratory distress and had systemic infiltration and pleural effusion. Positron emission tomography (PET)/computed tomography (CT) showed fluorine-18 deoxyglucose accumulation with maximum standardized uptake value ranging from 10 to 18 in bone marrow, liver, spleen, lung, and systemic lymph nodes (cervical, supraclavicular, infraclavicular, axillary, mediastinal, hilar, para-aortic, iliac, and inguinal). Left inguinal lymph node biopsy revealed mixed cellularity classical Hodgkin lymphoma (CHL), which was thought to be an FL transformation or a composite condition. The patient was treated with A + AVD and achieved lymph node shrinkage as well as improvement of tumor fever and pleural effusion. Interim PET/CT showed improvement in most parts after two courses; however, it revealed some new or progressive lesions in the bone marrow and left cervical lymph nodes. Left cervical lymph node biopsy revealed nodular sclerosis CHL. The patient was treated with ESHAP, which resulted in stable disease; following this, the patient was treated with nivolumab, which was highly effective. FL transformation to CHL is rare, and this is the first report of such transformation without treatment.

Insulin-like growth factor II-producing colonic carcinoma presenting with non-islet cell tumor hypoglycemia: An autopsy report revealing neuroendocrine differentiation in the metastatic foci and literature review.

Non-islet cell tumor hypoglycemia (NICTH) is a very rare symptom of severe hypoglycemia associated with extrapancreatic tumors. It is considered to be caused by insulin-like growth factor (IGF)-II. There have been no autopsy cases of colorectal carcinoma with NICTH confirmed with both serum high molecular weight and tumoral IGF-II. We report the case of a 46-year-old woman with advanced sigmoid colon cancer and liver metastases. She underwent open sigmoidectomy, and histologically, the lesion was a differentiated-type tubular adenocarcinoma. Postoperative chemotherapy was initiated. However, she experienced repeated hypoglycemia attacks 10 months after the operation, while the liver metastases increased. We examined the cause of hypoglycemia, and finally diagnosed her with NICTH associated with high molecular weight IGF-II production, which was proven by Western immunoblot of the serum. She died 12 months after surgery and was examined by autopsy. Liver metastases showed a transition from adenocarcinoma to carcinoma with neuroendocrine differentiation. Immunohistochemistry showed that both metastatic carcinoma of the liver and primary colonic adenocarcinoma were positive for IGF-II. Neuroendocrine differentiation in liver metastases proven by an autopsy may have contributed to tumor growth, which may have exacerbated the symptoms.

Acute tubulointerstitial nephritis in a patient with early bronchial tuberculosis.

Patients with chronic kidney disease (CKD) are commonly at high risk of tuberculosis (TB). Conversely, TB rarely causes tubulointerstitial nephritis. A 75-year-old Japanese man who was undergoing periodic follow-ups for CKD stage G3aA3 with membranous nephropathy was diagnosed with acute kidney injury (AKI) (estimated glomerular filtration rate [eGFR]: 15 mL/min/1.73 m2) without prerenal AKI. He reported developing recent-onset cough 3 weeks prior to presenting to us. Renal biopsy revealed acute tubulointerstitial nephritis along with known membranous nephropathy. CD4+ helper T cells comprised most lymphocytes in the tubulointerstitium. Results of the interferon-gamma release assay, sputum smear test, polymerase chain reaction (PCR), and culture test were positive for TB. Chest computed tomography revealed thickening of the left bronchial wall; therefore, a diagnosis of early bronchial TB was made; his urine culture and PCR were negative for TB. At four months after TB treatment with no immunosuppressive therapy, his eGFR improved to 50 mL/min/1.73 m2, and based on this progress, the AKI was diagnosed as tuberculosis-associated tubulointerstitial nephritis (TATIN). Although TATIN typically occurs with chronic or miliary tuberculosis, it is very rare in early bronchial TB. Identification of TATIN is important in kidney diseases of unknown etiology, and treatment with anti-TB drugs is necessary.

A new classification for the diagnosis of superficial non-ampullary duodenal epithelial tumors using endocytoscopy: A prospective study.

BACKGROUND AND AIM: Although the frequency of endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been increasing in recent years, no criteria for the endoscopic diagnosis of these tumors have been established yet. The aim of this study was to assess the usefulness of endocytoscopy for diagnosis SNADETs and to establish new criteria. METHODS: This prospective study was conducted at the NTT Medical Center Tokyo from May 2019 to July 2020, and a total of 100 consecutive SNADETs were enrolled. All the endocytoscopic images of the lesions and surrounding normal mucosa were classified into three groups according to the degree of structural atypia and the nuclear morphology and size. The endocytoscopic diagnoses using endocytoscopic classification was compared with the final histopathological diagnoses. RESULTS: Data of 93 patients with 98 lesions were included in the analysis. The preoperative diagnosis by endocytoscopy coincided with the final histopathological diagnosis in 85 (86.7%) of 98 SNADETs. In addition, the sensitivity and specificity for VCL 4/5 were 87.7% and 85.4%, respectively. In contrast, the accuracy, sensitivity, and specificity of preoperative diagnosis by biopsy were 64.3%, 50.9%, and 82.9%, respectively. Preoperative diagnosis by endocytoscopy showed significantly superior accuracy and sensitivity as compared with preoperative biopsy diagnosis (P < 0.001, respectively). CONCLUSIONS: This new classification (endocytoscopic classification) allows prediction of the tumor histopathology in real time, during endocytoscopy without biopsy, and is expected to be of help in determining the appropriate therapeutic strategies for individual cases of SNADETs. (Clinical trial registration number: UMIN000038643.).

Cystic Lesion of Dissected Pararectal Lymph Node in a Female Patient With Rectal Carcinoma: A Rare Pattern of Nodal Metastasis Mimicking a Serous Inclusion Cyst.

Nodal metastatic foci of colorectal carcinoma are usually solid nodules. Serous inclusions are occasionally found in lymph nodes, particularly in female patients, and they occasionally form cysts. An 86-year-old woman was treated with laparoscopic low anterior resection and D3 lymph node dissection for advanced rectal carcinoma. A cyst with serous fluid and no necrotic debris was found within one of the dissected pararectal lymph nodes. Histologically, the cyst was lined by low columnar-to-cuboid epithelium with mild nuclear atypia, mimicking a serous inclusion cyst. Immunohistochemically, the epithelial cells were positive for caudal type homeobox 2 and negative for Wilms' tumor suppressor gene1. Immunohistochemistry for p53 showed a diffuse strong positivity, indicating a mutant TP53 as seen in primary rectal carcinoma. Thus, the nodal cystic lesion was confirmed to be a metastatic lesion. It is important to carefully assess a nodal cystic lesion to confirm whether it is benign or malignant.

Large duodenal pyloric gland adenoma successfully resected by endoscopic submucosal dissection.

A 71-year-old woman was given a barium meal examination as part of a workup for recurring melena and iron deficiency anemia (IDA), and it revealed a large duodenal polyp measuring 60 mm in diameter. Subsequent upper gastrointestinal endoscopy showed a large pedunculated polyp in the duodenal bulb. Magnifying endoscopy with narrow-band imaging (NBI) showed that the lesion consisted of a regular enlarged intervening part between crypts of the epithelium that resembled gastric mucosa. Although the lesion was suspected of being benign, it was resected by endoscopic submucosal dissection (ESD) to prevent the progression of the IDA. The pathology examination revealed the proliferation of mildly irregular-shaped or dilated glands lined by cuboidal cells and low columnar cells in the submucosa. The gastric glands were immunohistochemically positive for MUC6, suggesting pyloric gland differentiation. The lesion was covered by a foveolar-type epithelium, and we made a diagnosis of pyloric gland adenoma (PGA). PGAs are most common in the stomach, and they are rare in the duodenum, where endoscopic treatment is technically challenging. Here we report a case of large duodenal PGA successfully resected by ESD. Since part of PGAs has been reported to be associated with adenocarcinoma, minimally invasive treatment strategies are desirable to reduce the risk of progression to carcinoma.

Clinicopathologic Characteristics of Esophageal Ectopic Sebaceous Glands: Chronological Changes and Immunohistochemical Analysis.

Esophageal ectopic sebaceous glands are very rare lesions. A series of 5 cases in a single report has been the maximum number described in the English literature to date. We conducted a clinicopathologic study of 8 cases of esophageal ectopic sebaceous glands. The median patient age at the time of diagnosis was 60 years (range, 50-71 years), and 7 of the 8 patients were male. A focal lesion was observed in 7 cases, whereas 1 case exhibited multiple lesions throughout the esophagus. Four patients had previously undergone upper gastrointestinal endoscopy; in 3 patients, the focal lesion had not been detected. After diagnosis, 3 cases showed spontaneous regression at least once. Immunohistochemically, sebocytes of all 8 cases were negative for the estrogen receptor (ER) and the progesterone receptor (PgR), whereas sebocytes of 5 cases were positive for the androgen receptor (AR). Basal/parabasal cells were positive for AR, ER, and PgR in 5, 7, and 4 cases, respectively. GATA3 was expressed in the sebocytes and basal/parabasal cells of 6 out of 7 available cases, whereas all of 7 available cases were negative for mammaglobin and GCDFP15. Our report provides the basic clinicopathologic characteristics of esophageal ectopic sebaceous glands by the largest case series reported in English literature to date. Furthermore, the chronological changes, particularly spontaneous regression, and immunohistochemical expression of hormone receptors and GATA3 are compatible with lesions resulting from congenital misplacement under hormonal regulation. Therefore, they seem to be congenital misplacements detectable as a result of hormonal stimulated growth.

Simple scoring system for the diagnosis of superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND AIMS: Differentiating superficial non-ampullary duodenal epithelial tumors (SNADETs) that harbor malignant potential is important. We developed a simple scoring system and investigated whether it enables the differentiation of low-grade adenoma and high-grade adenoma/adenocarcinoma. PATIENTS AND METHODS: We retrospectively enrolled 197 consecutive patients with 207 SNADETs who underwent endoscopic resection at NTT Medical Center Tokyo between March 2016 and May 2019. Endoscopic findings were compared between Vienna Classification (VCL) C3 and C4/5 lesions. A multivariate logistic regression analysis was performed to develop a scoring system to identify VCL C4/5 lesions. The efficacy of our scoring system was elucidated among five novice and five expert endoscopists. RESULTS: Of 207 SNADETs, 66 and 141 lesions were pathologically diagnosed as VCL C3 and C4/5. A multivariate logistic regression analysis identified a tumor diameter of 10-19 mm (OR, 3.81; 95% CI, 1.02-14.2; P = 0.04), a tumor diameter ≥20 mm (OR, 95.2; 95% CI, 10.4-871.0; P < 0.001), a red color (OR, 14.5; 95% CI, 3.55-59.6; P < 0.001), the presence of irregular surface pattern (OR, 12.4; 95% CI, 3.00-51.4; P < 0.001), and the presence of irregular vessel pattern (OR, 13.7; 95% CI, 4.03-46.6; P < 0.001) as independent significant predictors of VCL C4/5. Considering these results, we developed a scoring system. Using an appropriate cutoff value, the diagnostic accuracy, sensitivity and specificity were calculated as 92%, 95% and 93%. The average diagnostic accuracy did not differ between novice and expert endoscopists (86% vs 87%, P = 0.76). CONCLUSIONS: Our scoring system was useful for differentiating VCL C3 and C4/5 lesions. UMIN Clinical Trials (No. 000039063).

CD10-Negative Primary Breast Follicular Lymphoma: A Rare Case of Primary Breast Lymphoma With an Atypical Immunophenotype Mimicking Marginal Zone Lymphoma.

In this article, we report the case of a 78-year-old woman who consulted our hospital for a right breast mass detected on mammography during her cancer screening. Biopsy specimens showed atypical lymphocytic infiltration with a follicle-like growth pattern, suggesting a follicular lymphoma (FL). Immunohistochemically, the atypical lymphoid cells were diffusely and strongly positive for CD20, BCL2, and BCL6, but negative for CD10. IGH-BCL2 translocation was confirmed by fluorescence in situ hybridization analysis, leading to the diagnosis of primary breast FL. The most important differential diagnosis of this case was marginal zone lymphoma (MZL), which usually shows a CD10-/BCL2+ immunophenotype and is one of the common histological types in primary breast lymphomas. FLs with an atypical immunophenotype exist in a certain percentage of patients. Therefore, FL is considered to be a heterogeneous entity. It is important to distinguish FL from MZL in primary breast lymphomas because FLs may have a worse prognosis than MZLs.

Uterine cervical squamous cell carcinoma with reactive multinucleated giant cells expressing cluster of differentiation 204: A case report and literature review.

Uterine cervical squamous cell carcinoma (SCC) with reactive multinucleated giant cells (MGC) is extremely rare. Here we present the case of a 49-year-old woman treated with radical hysterectomy, bilateral adnexectomy and lymph node dissection. Histologically, the cervical tumor was diagnosed as nonkeratinizing SCC of pT1b1N0M0, with negative surgical margin. Many MGC including osteoclast-like giant cells with immunohistochemical expression of cluster of differentiation 204, a marker for the M2 macrophage, were present around the tumor nests. The patient received postoperative radiation therapy and achieved 22 months of disease-free survival after the surgery. M2 macrophages promote aggressiveness of the carcinoma and it is suggested that SCC of the cervix with reactive MGC might have poor prognosis; however, our case paradoxically showed a favorable course. From literature review of six cases, including our case, the effect of MGC-reaction may vary with respect to other factors, such as age, cancer stage or histological type.

Progressively increasing density of the solid center of a ground-glass nodule in a solitary pulmonary capillary hemangioma: A case report.

Solitary pulmonary capillary hemangiomas (SPCHs) are recently recognized, rare benign lesions that form solitary nodules owing to capillary proliferation. These lesions are usually detected incidentally as small ground-glass nodules (GGNs) on computed tomography (CT), and progressively enlarge over time. The radiological distinction from peripheral lung cancers is particularly challenging. However, to date, there have been no reports on progressive changes in the central density of SPCH on CT. An asymptomatic 49-year-old man was referred to our hospital for an abnormal shadow that was detected on chest CT during medical check-up. He was subsequently followed-up with chest CT. The nodule increased in size, and the central area became progressively denser. He underwent surgery 5 years and 10 months after the first visit owing to suspicion of lung cancer. Despite the collapse of the surgical specimen by artifacts, histopathological examination revealed a diagnosis of SPCH; collagenous fibers were found in the walls of the intralesional capillaries. The patient is presently alive without any recurrence, 6 months after the operation. In this case, the SPCH demonstrated a GGN with progressively increasing density of the central solid area on the CT. This remarkable feature made the preoperative distinction from lung cancer particularly difficult.

Colonic Neurogenic Lesion: An Admixture of Mucosal Neurofibromatous Lesion and Submucosal Ganglioneuromatous Lesion With Transition.

Benign neural tumors or tumor-like lesions are rarely detected in the gastrointestinal tract. In this article, we present the case of a neural lesion of the sigmoid colon, which was incidentally detected in a 68-year-old man treated with laparoscopic low anterior resection for an advanced carcinoma of the rectosigmoid junction. Within the resected specimen, a submucosal tumor-like protruding lesion was found in the sigmoid colon. Histologically, the growth was composed of mucosal neurofibromatous and submucosal ganglioneuromatous lesions, between which there was transition. Immunohistochemical analysis revealed a rupture of the perineurium in the area of transition, along with a proliferation of Schwann cells and supporting cells extending into the deep mucosa. This transition indicated that the mucosal and submucosal lesions comprised a single lesion, and that a diagnosis of neurofibroma or ganglioneuroma would be inadequate in this case. Because we could not classify it as an established single entity, we diagnosed the mass as an unclassifiable colonic neurogenic lesion. In summary, we report the case of an extremely rare occurrence of an unclassifiable colonic neurogenic lesion comprising an admixture of transitioning mucosal neurofibromatous and submucosal ganglioneuromatous lesions.

Myocardial calcification in a patient with B-lymphoblastic leukemia accompanied by tumor lysis syndrome.

Myocardial calcification, a rare disease that leads to chronic or acute heart failure and with a poor prognosis, occurs in patients with abnormal calcium-phosphorus metabolism. The association between myocardial calcification and tumor lysis syndrome has not been reported to date. A 50-year-old man with hyperthermia and general malaise presented to our hospital and was clinically diagnosed with B-lymphoblastic leukemia (B-ALL) and febrile neutropenia accompanied by septic shock. Prednisolone was administered for tumor reduction. Two to three hours later, electrocardiography demonstrated ST elevation in V4-6, and blood tests showed elevated levels of cardiac enzymes. Transthoracic echocardiogram revealed diffuse severe hypokinesis with decreased left ventricular ejection fraction. Additionally, blood tests showed that serum phosphorus level increased to 8.0 mg/dl, which was likely due to tumor lysis syndrome. Circulatory and respiratory failure due to left heart failure progressed, and he died 3 days after administration of prednisolone. Pathological autopsy revealed diffuse proliferation of atypical B-lymphoblasts in the bone marrow, which led to the pathological diagnosis of B-ALL, accompanied by necrosis. On the cut surface of the heart, the left ventricle was dilated, and patchy yellowish-brown areas were present in the epicardial-side of the myocardium and spread through the circumferential wall of the left ventricle and interventricular septum. Microscopically, myocardial fibers were granularly basophilic in that area and were revealed as calcium deposits by Von Kossa staining. He was diagnosed with myocardial calcification. The drastic increase in the serum phosphorus level caused by tumor lysis syndrome seemed to be associated with myocardial calcification.

Intrahepatic Carcinosarcoma With Cholangiocarcinoma Elements and Prominent Bile Duct Spread.

Carcinosarcomas with elements of cholangiocarcinoma and sarcoma are rare and have a poor prognosis. The spreading pattern and radiological findings of these lesions remain unclear. A 74-year-old man presented with a high γ-glutamyl transferase level. Magnetic resonance imaging revealed dilation of the right intrahepatic and common bile ducts, consistent with an intraductal papillary neoplasm of the bile duct (IPNB), and diffusion-weighted imaging (DWI) indicated an area of high signal intensity in the intrahepatic bile duct. Bile duct biopsy yielded a small amount of atypical spindle cells, and the patient underwent a right hepatectomy. Microscopically, the tumor contained cholangiocarcinoma and sarcomatous components, including osteosarcoma and leiomyosarcoma, leading to a diagnosis of intrahepatic carcinosarcoma. The tumor spread primarily through the intrahepatic bile duct. An accurate radiological diagnosis of carcinosarcoma was challenging, given the apparent similarities with IPNB. The findings from DWI and pathology of a bile duct biopsy may assist with preoperative diagnosis.

Cerebral amyloid-ß-related angiitis without cerebral microbleeds in a patient with subarachnoid hemorrhage.

Amyloid-ß-related angiitis (ABRA), a subtype of cerebral amyloid angiopathy (CAA), is vasculitis occurring in relation to amyloid-ß (Aß) deposition in the walls of intracranial blood vessels. ABRA is presumed to be caused by some immune response to the deposited Aß. An 81-year-old man on oral anticoagulant therapy complained of headache, nausea, and difficulty with standing after a head injury. Head computed tomography revealed subcortical bleeding in the right temporoparietal lobe, and 3 days after admission, magnetic resonance imaging (MRI) showed subarachnoid hemorrhage (SAH) around the hematoma. Cerebral microbleeds, a characteristic of CAA, were not detected on MRI. On worsening of his symptoms, intracranial brain biopsy and hematoma removal were performed. Intraoperative rapid diagnosis with a frozen section suspected vasculitis, which enabled the prompt initiation of steroid therapy. He was pathologically diagnosed with ABRA (granulomatous angiitis) using a formalin-fixed paraffin-embedded section. Vasculitis was prominent around blood vessels in the pia matter covering the cerebrum. In this case, the inflammatory cells seemed to appear via the subarachnoid space following cerebral hemorrhage and SAH. ABRA seemed to be developed by intracranial hemorrhage in this case.