[A Case of Aldosterone-Producing Adrenocortical Carcinoma].

A 59-year-old man presented with high blood pressure, hypokalemia and muscle weakness. His aldosterone/renin ratio was high and plasma renin activity was low. Computed tomography (CT) showed a heterogeneous left adrenal mass. Primary aldosteronism was diagnosed and laparoscopic left adrenalectomy was performed. The pathological diagnosis was adrenocortical carcinoma with positive surgical margins. He underwent radiotherapy and mitotane as adjuvant therapies. Subsequently, CT revealed multiple metastases, in the liver and retroperitoneum. After six courses of EDP (a combination of etoposide, doxorubicin and cisplatin), CT showed widespread metastases in the retroperitoneum and he chose to receive the best supportive care. Aldosterone-producing adrenocortical carcinoma is exceedingly rare. To the best of our knowledge, only67 cases have been reported. Complete resection is needed to improve prognosis and this was not achieved in our case. We therefore recommend careful selection of the operative procedure.

[A Case of Multiple Penile Schwannoma].

A 48-year-old man presented with a painless nodule on the right ventral aspect of the penile shaft root. The patient visited the hospital and complained that the mass was growing. On physical examinations, a 5 cm mass without tenderness was palpated. An isoechoic mass about 4 cm in size was observed on ultrasonography. Inhomogeneous high signal intensity was observed on T2-weighted magnetic resonance imaging. A needle biopsy revealed schwannoma. During surgery for excision of the tumor, another small tumor was detected both tumors were resected. Both tumors were diagnosed as schwannoma by pathological examination. Out of 40 cases of penile schwannoma reported, eight were of multiple tumors. In our case, it was difficult to detect the other small tumor by preoperative diagnosis. Therefore, we recommend careful observation during surgery.

Utility of a new notation to visualize flow cytometry analysis results: first preliminary comparison with immunohistochemistry to detect CD30 expression on T-cell lymphoma cells.

BACKGROUND: It is important to confirm CD30 expression in T-cell lymphoma cases, but immunohistochemical staining for CD30 is not commonly performed and no comparison has been done between the results of flow cytometry (FCM) and immunohistochemical staining for CD30. Therefore, we devised a notation that we termed proportion of immunoreactivity/expression for FCM (PRIME-F notation), based on the cellular proportion showing different antigen-antibody reactivity. METHODS: We retrospectively compiled 211 cases of T-cell lymphoma, assessed via FCM, from major hospitals in Miyagi Prefecture from January 2012 to January 2019, and compared 52 of these cases with the immunohistochemical immunoreactive (IR) pattern of CD30 (PRIME-I notation). The PRIME-F notation was divided into five levels: notations starting with "-" followed by 3, 2, and 1 ">" correspond to level-I, level-II, or level-III; notations starting with "(dim)+" correspond to level-IV; and those starting with "+" or "(bright)+" correspond to level-V. RESULTS: The 52 cases of PRIME-F notation with "+" included 16 cases of peripheral T-cell lymphoma (PTCL/NOS), 3 of follicular T-cell lymphoma (FTL), 3 of angioimmunoblastic T-cell lymphoma (AITL), 6 of extranodal NK/T-cell lymphoma/nasal type (ENKL), 18 of adult T-cell lymphoma (ATL), and 6 cases of anaplastic large cell lymphoma (ALCL). Eight of the 52 cases were immunohistochemically CD30-negative. In the PRIME-F level-I to III group (excluding false-positive cases), 21.7% (5 out of 23 cases) were < 10% positive for CD30 upon immunohistochemistry (IHC). Contrarily, in the level-IV & -V group, no CD30 positivity rate of < 10% upon IHC was found (0%) (p = 0.0497). In level-IV, 42.9% of cases presented a CD30 negative rate > 1/3 upon IHC, while in level-V, only 7.1% (one out of 14 cases) did. The CD30 negative rate tended to be low (p = 0.0877) in level-V. CONCLUSIONS: To our knowledge, this is the first report describing the correspondence between FCM and immunohistochemistry findings for CD30 through newly proposed notations. The PRIME-F and PRIME-I notations for CD30 showed a minor positive correlation. The PRIME notation is considered universally applicable to antibodies, and notations of both FCM and IHC show great potential for big data.

[A Case of Ureteral Metastasis from Prostate Cancer].

Ureteral metastasis from prostate cancer is rare. The present case report describes an 83-year-old patient with distant metastasis of prostate cancer to the right ureter that caused hydronephrosis. Upon initial examination at our hospital, he presented with a high prostate-specific antigen (PSA) level of 10.0 ng/ml. He was diagnosed with prostate adenocarcinoma, with Gleason score of 10 (5＋5) and clinical staging of cT2aN0M0. Intensity-modulated radiation therapy (IMRT) was performed after 1 year and 7 months of androgen depriation therapy. At 1 year and 4 months after IMRT, PSA increased to 3.068 ng/ml. Computed tomography scan revealed right hydronephrosis and thickening of the right ureter. We could not identify obvious malignant cells on ureteroscopic biopsy, and right nephroureterectomy was performed. Pathological examination revealed ureteral metastasis of prostate cancer. Six months after nephroureterectomy, PSA increased to 3.037 ng/ml. He was diagnosed with castration-resistant prostate cancer and has been treated with enzalutamide.

Extraordinarily long-inactive solitary fibrous tumor transformed to produce big insulin-like growth factor-2, leading to hypoglycemia and rapid liposarcoma growth: a case report.

BACKGROUND: A high-molecular-weight form of insulin-like growth factor-2 (IGF-2), known as "big" IGF-2, is occasionally produced by various tumor types, leading to hypoglycemia. Although solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm, it has been estimated that 4-6% of SFT patients develop hypoglycemia due to circulating big IGF-2. The mean time elapsed from tumor detection until the onset of hypoglycemia is reportedly less than one year (8.5 ± 1.9 months). CASE PRESENTATION: A 68-year-old man was hospitalized for exacerbation of recurring hypoglycemic episodes. He had been diagnosed with an SFT 17 years before the onset of hypoglycemia, and the SFT had already been very large at that time. The tumor, which was non-resectable and refractory to chemotherapies, had slowly increased in size since the initial diagnosis. Half a year before the hypoglycemic episodes manifested, another tumor, adjacent to the left kidney, was newly identified. Fluorodeoxyglucose positron emission tomography-computed tomography scanning, revealed the left peri-renal tumor to show much higher fluorodeoxyglucose uptake than the preexisting SFT, suggesting that it was unlikely to be a metastasis from the SFT. Abundant serum big IGF-2 was detected by western immunoblot analysis, indicating it to be the cause of the hypoglycemia. Since the 17 years between SFT detection and the onset of IGF-2-induced hypoglycemia was an extremely long period as compared with those in previous reports, we initially suspected that the new, peri-renal tumor had produced big IGF-2, but transcatheter arterial embolization of its feeding arteries did not suppress hypoglycemia. Notably, by measuring the tumor volume doubling time, the peri-renal tumor growth was shown to be markedly accelerated in parallel with exacerbation of the hypoglycemia. The patient died of heart failure 21 months after the onset of hypoglycemia. Unexpectedly, autopsy revealed that big IGF-2 had been produced only by the preexisting SFT, not the peri-renal tumor, and that the peri-renal tumor was a dedifferentiated liposarcoma. CONCLUSIONS: We should keep in mind that even a long-inactive SFT can undergo transformation to produce big IGF-2, which then acts on both insulin and IGF-1 receptors, possibly leading to both hypoglycemia and the development/growth of another tumor, respectively.

A ganglion-rich gastrointestinal stromal tumor: A case report.

We report a case of an extremely rare type of duodenal gastrointestinal stromal tumor (GIST) that included neuronal components. Although gastrointestinal autonomic nerve tumors (GANTs), a subtype of GISTs, exhibit ultrastructural features of the nerve plexus, neuronal cells have not been observed within GANTs or GISTs. GISTs originate from interstitial cells of Cajal (ICCs), which are markedly different from the progenitor cells of neural elements and neural-crest-derived stem cells. This may explain why GISTs typically lack neuronal elements. It remains unclear that the neuronal components of this tumor are neoplastic or hyperplastic, but proliferation and survival of ICCs have recently been reported to be closely related to neurons. Although we could not find the KIT, PDGFR, and BRAF mutation as far as we examined, it may have had a rare mutation in NF1, a fusion of EVT6-NTRK3, or an as-yet-unknown KIT mutation that affected neurogenesis. Further investigation of related genetic mutations and accumulation of data from other similar cases is needed.

Incidence Rate, Subtype Frequency, and Occurrence Site of Malignant Lymphoma in the Gastrointestinal Tract: Population-Based Analysis in Miyagi, Japan.

Primary gastrointestinal lymphoma (PGIL) has been reported in many studies of lymphomas of the gastrointestinal tract worldwide. However, there have been few accurate population-based reports on lymphomas, and it is difficult to apply the strict definition of PGIL to all lymphomas occurring in the gastrointestinal tract. Accordingly, instead of using PGIL, this study included newly diagnosed lymphomas with biopsy or excision specimens obtained from the gastrointestinal tract (GI-related lymphomas) and aimed at presenting the incidence rate, subtype frequency, and occurrence site of GI-related lymphomas. Additionally, we examined GI-related lymphomas diagnosed using flow cytometry (FCM) analysis, cytogenetics analysis, and molecular analysis (multimetric and/or integrated analysis). We extracted data on GI-related lymphomas from 2,098 lymphoma cases registered from the entire Miyagi Prefecture in Japan. The number of GI-related lymphomas was 350, and the incidence rate was 2.97 per 100,000 persons. Diffuse large B-cell lymphoma was the most common subtype (47.4%), followed by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (32.6%) and follicular lymphoma (8.3%). The stomach was the most common site (62.6%), followed by the large intestine (15.4%), small intestine (14.3%), and duodenum (6.0%). Of the 350 included cases, 111 were diagnosed using multimetric and/or integrated analysis, in which the proportions of positive results for FCM analysis, cytogenetics analysis, and molecular analysis were 81%, 33%, and 51%, respectively. These results may provide a representation of lymphomas occurring in the gastrointestinal tract in Japan. Multimetric and/or integrated analysis of GI-related lymphomas could enable us to acquire useful information for the diagnosis.

Association between BACH2 expression and clinical prognosis in diffuse large B-cell lymphoma.

BACH2, a B cell-specific transcriptional repressor, plays a significant role in B cell maturation. Despite a number of previous studies, the clinicopathological significance of BACH2 expression in diffuse large B cell lymphoma (DLBCL) remains to be established. The present study was performed to validate the significance of BACH2 expression as a predictor of prognosis in DLBCL. A total of 94 DLBCL cases were included in the present study. All were diagnosed between 2008 and 2011, and thorough clinical and pathological investigations were possible, including immunohistochemical analysis of BACH2. Eighteen cases were selected by positive MYC gene alteration (MYC+ group) according to cytogenetic study. The remaining 76 cases were subclassified into germinal center B cell phenotype (GCB group, 38 cases) or non-GCB phenotype (non-GCB group, 38 cases). There were no significant differences between the two groups with regard to clinical characteristics and outcomes. In the GCB group, 21 cases were judged to have high BACH2 expression, with 19 cases in the non-GCB group. In cases with high BACH2 expression in GCB and non-GCB groups, the 3-year overall survival (OS) rate was significantly shorter than that with low expression (71.7% vs 91.3%, P = 0.0256). In the MYC+ group, 15 cases had high BACH2 expression levels. Although overall the MYC+ group showed short survival time (3-year OS 35.0%), 3 out of 4 cases with low BACH2 expression are alive without disease relapse at the time of publication of this paper. In conclusion, BACH2 expression level is a promising predictor of prognosis for DLBCL.

Myopericytoma in the corpus cavernosum of the penis: A case report of a rare disease.

Introduction: Myopericytomas usually occur in the extremities of older individuals; however, they also rarely occur in the penis. We report a case of myopericytoma in the corpus cavernosum of the penis and review the relevant literature. Case presentation: A 76-year-old man presented with a slow-growing painless nodule on the left side of the penis. On physical examination, a non-tender, 7-mm mass was palpable. This tumor showed inhomogeneous low signal intensity on T2-weighted magnetic resonance imaging. The mass was excised and a myopericytoma diagnosed by pathological examination of the operative specimen. Conclusion: We here report a rare case of myopericytoma in the corpus cavernosum of the penis. To the best of our knowledge, this is the second reported case of a myopericytoma in the penis and the first in the corpus cavernosum of the penis. Clinicians should keep this rare possibility in mind when investigating a mass in the penis.

Intraosseous metaplastic meningioma: A case report.

Metaplastic meningioma is a rare World Health Organization Grade I meningioma subtype, accounting for 0.2%-1.6% of all meningiomas. Primary extradural meningiomas represent less than 2% of all meningiomas, with intraosseous meningioma as a subtype of primary extradural meningiomas. Herein, we report the case of a 65-year-old male presenting with headache. His computed tomography scans showed an osteolytic left parietal bone mass, and magnetic resonance imaging revealed hyperintense dots in the mass on T1-weighted images. The mass was then resected and diagnosed on histopathological examination as an intraosseous metaplastic meningioma.

Detection of Anaplastic Lymphoma Kinase-Rearranged Mesothelioma Cells in Ascites by Companion Diagnostics.

BACKGROUND: A case of peritoneal mesothelioma with an anaplastic lymphoma kinase (ALK) translocation was identified, and we conducted further studies to obtain diagnostic and therapeutic insights. We believe that this is the first report describing the cytology of this new tumor type. CASE: A teenage woman was referred for severe pleural effusion. Enhanced computed tomography indicated an abdominal mass with ascites. Laparoscopy revealed tumor dissemination from the pelvis to the upper abdomen. Because a high-grade serous carcinoma was suspected, ascitic cytology and biopsy were performed. Cytologically, the tumor displayed characteristics of both adenocarcinoma and reactive or neoplastic mesothelial cells. After extensive pathological evaluation, the tumor was diagnosed as malignant peritoneal mesothelioma. To verify the diagnosis and aid in developing a therapeutic strategy, several companion diagnostics were tried. Surprisingly, the tumor was ALK-positive, and ALK recombination was confirmed by an ALK break-apart test. Retrospectively, cells and tissue specimens were stained with ALK intercalated antibody-enhanced polymer. Tumor cells were clearly distinguished from the nonneoplastic background. Recombination in ALK was reconfirmed by the National Cancer Center Japan, and the patient was enrolled in a clinical trial for alectinib. CONCLUSION: Companion diagnostics-based cytology may provide a useful means of monitoring and evaluating a molecular-targeted therapy.

Immunohistochemical pattern of c-MYC protein judged as "+/(weak)+/-" by a new notation correlates with MYC gene nontranslocation in large B-cell lymphoma.

Immunohistochemistry is not only the most important tool for pathologists to establish a final diagnosis, but it can also inform decisions regarding optimal treatment methods. However, there is no universal standard notation for expressing immunohistochemical findings. For a diagnosis of malignant lymphoma, it is important to confirm the presence or absence of MYC translocation and communicate these results to a clinical audience. However, the criteria for selecting cases for fluorescence in situ hybridization (FISH) analysis to confirm MYC translocation are ill defined. We therefore devised a notation that we termed proportion of immunoreactivity/expression for immunohistochemistry (PRIME notation) based on the cellular proportion showing different antigen-antibody reactivity in immunohistochemistry (CPAR) and used it to examine the relationship between MYC translocation and the proportion of c-MYC+ lymphoma cells. We reviewed 82 cases diagnosed as diffuse large B-cell lymphoma or diffuse large B-cell lymphoma coexisting with grade 3A to 3B follicular lymphoma. The most common notation was "+/(weak)+/-" (49/82 cases [59.8%]); cases that were CPAR positive, weakly positive, and negative for tumor cells each accounted for about one-third of the total. Unexpectedly, no MYC translocation was observed by FISH in this group. Thus, FISH is not needed even if more than half of cells are c-MYC positive by PRIME notation. This is the first report describing a correspondence between immunohistochemical findings and chromosomal abnormality, reflecting findings at the protein and gene levels, respectively.

A case study of t(14;22)(q32;q11) involving immunoglobulin heavy and light chain in follicular lymphoma.

Chromosome 14 is the most frequently rearranged chromosome in non-Hodgkin lymphoma (NHL), with aberrations particularly involving the heavy-chain immunoglobulin gene (IGH) in the chromosome band 14q32. Several translocation partners have been described: t(14;18)(q32;21)/IGH-BCL2 in follicular lymphoma (FL), t(11;14)(q13;q32)/CCND1-IGH in mantle cell lymphoma, and t(8;14)(q24;q32)/MYC-IGH in Burkitt lymphoma. The chromosomal locus 22q11 contains two important genes associated with leukemia and lymphoma; one is BCR, which fuses with ABL from 9q34 in chronic myeloid leukemia, and the other is the immunoglobulin lambda gene (IGL), which is rarely involved in the translocations observed in B-cell NHL. The t(14;22)(q32;q11) translocation has been previously reported in 8 cases of B-cell NHL; however, the translocation between IGH and IGL has been experimentally confirmed using fluorescence in situ hybridization (FISH) for only 4 cases. Here, we describe the first case of FL with a t(14;22)(q32;q11)/IGH-IGL translocation confirmed using FISH analysis. The patient in our case report was immunocompromised and was treated for aplastic anemia with cyclosporine A (CsA). The patient was diagnosed with follicular lymphoma, most likely caused by CsA.

Successful Cord Blood Stem Cell Transplantation for Primary Cutaneous CD8-positive Aggressive Epidermotropic Cytotoxic T-cell Lymphoma Complicated with Cerebral Infiltration.

A 16-year-old boy, who had been initially examined for bilateral blepharedema and slight eruption, presented with rapidly deteriorating symptoms in associating with headache and consciousness disturbance. He was diagnosed to have primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (PCAE-CTL) by a biopsy of the skin and brain. After whole-brain radiation and some courses of chemotherapy, cord blood transplantation was performed with myeloablative conditioning. After transplantation, the cerebral dysfunction gradually improved. Disease remission was confirmed by the disappearance of any abnormal findings on electroencephalogram and magnetic resonance imaging. PCAE-CTL is reported to be an extremely aggressive disease with a poor prognosis, but the timely performance of cord blood transplantation is considered to be a promising treatment strategy.

Non-biased and complete case registration of lymphoid leukemia and lymphoma for five years: a first representative index of Japan from an epidemiologically stable Miyagi Prefecture.

Previous worldwide epidemiological studies on lymphoid leukemia and/or lymphoma (LL/L) had considerable bias because of difficulty in covering all clinical departments of hospitals in a restricted area (population base). These studies may not have reflected the actual number of newly diagnosed cases (incidence) strictly, or the true LL/L subtype frequencies. We searched all cases of newly diagnosed LL/L in Miyagi Prefecture over a 5-year period, including those that were discovered as LL/L sorely after autopsy. We registered the actual number of 2098 cases in the prefecture and calculated an accurate incidence rate (17.8 per 100,000 persons). Additionally, we identified more realistic and detailed frequencies of LL/L subtypes including the leukemic phase of some lymphomas. As Miyagi Prefecture is an area in which the population dynamics are relatively stable and representative of Japan, the result of our epidemiological study can be used as the first representative index of LL/L for Japan.

Advanced Lymphocyte-rich Classical Hodgkin Lymphoma Complicated with Fatal Hemophagocytic Syndrome.

Lymphocyte-rich classical Hodgkin lymphoma (LRCHL) is a rare subtype of Hodgkin lymphoma with a favorable prognosis, and an aggressive clinical course of LRCHL is uncommon. A 55-year-old man suffering from swelling in the left neck was diagnosed with LRCHL with extranodal lesions in the lung and bone marrow. Initially, he received standard ABVD chemotherapy; however, disease progression, accompanied by hemophagocytic syndrome (HPS), occurred during the second course of ABVD. He received two subsequent courses of intensive chemotherapy containing high-dose steroids, cyclophosphamide, and etoposide. Nevertheless, this therapy was only temporarily effective, and he died of due to an aggressive disease progression accompanied by uncontrollable HPS and severe coagulopathy.

Clinicopathological analysis of primary adrenal diffuse large B-cell lymphoma: effectiveness of rituximab-containing chemotherapy including central nervous system prophylaxis.

BACKGROUND: Primary adrenal lymphoma (PAL) is an extremely rare subtype of extranodal non-Hodgkin's lymphoma. Some researchers have reported some of the characteristics of PAL and its association with poor prognosis; however, the clinicopathological features of PAL remain to be elucidated. METHODS: From 2008 to 2011 we experienced seven cases of PAL in our institutions. We retrospectively analyzed the clinical and pathological features of these patients. RESULTS: The patients ranged in age from 50 to 85 years, with a median of 71 years. The overall male:female ratio was 6:1. All seven patients were diagnosed with diffuse large B-cell lymphoma (DLBCL) pathologically. Bilateral adrenal involvement was confirmed in five patients. The median largest tumor diameter at diagnosis was 58 mm. The Ki-67 index was generally high (>70%). All patients were treated with rituximab-containing chemotherapy, and central nervous system (CNS) prophylaxis was conducted for three patients. One patient with CNS involvement at the time of the diagnosis also received whole-brain radiation. The overall survival rate at two years was 57% (median follow-up; 24.8 months). It is noteworthy that the three patients who received a full course of the rituximab-containing regimen and CNS prophylaxis are currently alive without disease relapse, and that none of the seven patients died due to progression of lymphoma. CONCLUSIONS: Primary adrenal DLBCL can be a clinically aggressive disease entity. Rituximab-containing chemotherapy combined with CNS prophylaxis could be a reasonable option for the treatment of PAL; however, analyses of more PAL cases are needed for the establishment of this strategy.