A rare involvement in skin cancer: Merkel cell carcinoma with bone marrow infiltration in a kidney transplant recipient.

A 60-year-old man presented with a painless, rapidly growing, haemorrhagic pink nodule on the posterior of his thigh that had developed 1 month previously. He had a diagnosis of IgA nephropathy and had received a renal allograft 7 years before. An excisional biopsy was performed and the diagnosis of Merkel cell carcinoma (MCC) was made. No distant metastases was detected. 10 months after first presentation, due to the development of acute pancytopenia and concomitant FDG PET/CT findings compatible with disease progression, bone marrow biopsy was performed which revealed metastasis of MCC. Dermatologists and oncologists should be aware that MCC could potentially involve the bone marrow in organ transplant recipients. In the follow-up period, a complete blood count should be carried out; FDG PET/CT can be obtained to follow up the metabolic status of the disease and bone marrow biopsy should be performed if necessary.

Differences and similarities of proliferative and non-proliferative forms of biopsy-proven lupus nephritis: Single centre, cross-disciplinary experience.

OBJECTIVE: We aimed to compare clinical features, outcomes, treatments, and to define the predictive factors of complete renal response (CRR) in patients with proliferative and non-proliferative lupus nephritis (LN). METHODS: Patients with systemic lupus erythematosus (SLE) followed between 2014 and 2020 at Hacettepe University Hospitals and who had a kidney biopsy were the subject of the study. One hundered and sixteen patients' kidney biopsies reported as LN were evaluated retrospectively. Clinical characteristics and laboratory values at the time of kidney biopsy, histopathological forms of LN, and renal response (complete or partial) were recorded. We analyzed the association between CRR rates during the 2-year follow-up after induction therapy and the predictive factors for CRR. RESULTS: Of 116 (93 females, 23 males) patients, 95 (81.9%) were in the proliferative group (class III and IV) and 21 (18.1%) were in the non-proliferative group (class II and V). In the proliferative group, the percentage of the patients with elevated basal creatinine levels, median daily proteinuria, anti-double-stranded DNA (dsDNA) positivity, low C3 and C4 levels, the presence of active urinary sediment, and median renal SLE Disease Activity Index (SLEDAI) scores at the time of kidney biopsy were significantly higher than the non-proliferative group. Renal response status during the 2-year follow-up after induction therapy was available for 99 patients. During this time, 70 (70.7%) patients had achieved CRR and time-to-CRR was similar between the proliferative and non-proliferative groups (p = 0.64, log-rank test). The Cox proportional hazards model showed that achievement of CRR was associated with female gender [HR: 2.15 (1.19-3.89 95% CI), p = 0.011], newly diagnosed SLE with renal biopsy [HR: 2.15 (1.26-3.67 95% CI), p = 0.005], hypertension [HR: 0.40 (0.27-0.94 95% CI), p = 0.032], eGFR increase [HR: 1.01 (1.00-1.01 95% CI), p = 0.046], and the presence of active urinary sediment [HR: 0.46 (0.22-0.96 95% CI), p = 0.039]. CONCLUSIONS: Achieving CRR was similar in proliferative and non-proliferative LN patients, although certain laboratory parameters differed at the onset. Our results indicated the importance of kidney biopsy in the decision-making of treatment of SLE patients with renal involvement and that the defined factors associated with CRR achievement help to predict good renal response.

Case Report: Castleman Disease With an Associated Stromal Spindle Cell Proliferation, PDGFRB Mutation and p53 Expression: Clonal Origins of a Rare Disease.

Castleman disease (CD) is a rare lymphoproliferative disorder with distinct clinical subtypes. However, our understanding of the underlying pathogenesis of particular subtypes of CD remains unclear. While the characteristic morphologic changes within UCD, including occasional cases of overgrowth of spindled stromal and follicular dendritic cells have been described, the nature and origin of these spindle cells remain elusive. Few reports have suggested that underlying stromal cells in UCD are clonally neoplastic and may be of fibroblastic reticular cell (FRC) or follicular dendritic cell (FDC) origins given their close clonal relationship. Although certain histomorphologic features may aid diagnosis, there are no specific biomarkers that can differentiate a reactive process mimicking UCD from true UCD. Hence, we describe an index case with morphology consistent with the hyaline vascular subtype of UCD with concomitant atypical smooth muscle actin (SMA)-positive stromal spindle cell proliferation containing a recurrent PDGFRB N666S mutation and upregulation of p53 expression. Further analysis of 21 additional cases of UCD identified increased p53 expression by digital image analysis and SMA positive stromal cells predominantly within the paracortical and intrafollicular areas further strengthening the hypothesis of the stromal cellular derivation and origins of UCD.

Dismal Prognosis of Acute Allergic Tubulointerstitial Nephritis in Patients with AA Amyloidosis.

INTRODUCTION: Patients with AA amyloidosis may present with acute kidney injury that progresses to end-stage kidney disease in a short period of time. Acute allergic tubulointerstitial nephritis (aTIN) is a frequent cause of acute kidney injury in patients with AA amyloidosis. Although aTIN has a favorable prognosis in the general population, the course of aTIN in patients with AA amyloidosis was not previously reported. In this retrospective study, we determined the prognosis of aTIN superimposed on AA amyloidosis. METHODS: Thirty-two patients with combined pathological diagnosis of AA amyloidosis + aTIN and 32 patients with isolated aTIN were compared in terms of 1-year renal functions after the biopsies were performed with an indication of acute kidney injury. Baseline renal functions and number of patients requiring hemodialysis at the time of biopsy was similar in both groups. RESULTS: At the end of the 12-month follow-up period, 29 of 32 patients in the amyloidosis + aTIN group and 1 of 32 patients in the isolated aTIN group required dialysis. Most of these patients with AA amyloidosis had completely normal renal function before the episode of acute kidney injury and had clear exposures to drugs associated with aTIN. CONCLUSION: In contrary to the patients without AA amyloidosis, patients with AA amyloidosis have extremely high risk of permanent renal failure in case of development of aTIN. Great caution should be exercised in prescribing drugs that are associated with aTIN, in patients with AA amyloidosis.

Ghosal hematodiaphyseal dysplasia with autoimmune anemia in two adult siblings.

Ghosal hematodiaphyseal dysplasia (GHDD) is an autosomal recessive inherited disorder associated with biallelic mutations in the TBXAS1 gene located on the chromosome 7q33-34, which encodes thromboxane-A-synthase. GHDD is characterized by defective hematopoiesis due to bone marrow fibrosis and metadiaphyseal dysplasia of long bones. The accurate diagnosis of this rare syndrome is critical since it reduces the need of blood transfusions by corticosteroid therapy, leading to a significant improvement in anemia and bone changes. The aim of this study is to report two adult siblings diagnosed as GHDD, who admitted with pancytopenia and treated with steroids treatment in adult hematology clinic.

A unique case of complex variant translocation of t(6;9;22)(p22;q34;q11.2), der(19) in a newly diagnosed patient with chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the dysregulated production and uncontrolled proliferation of myeloid neoplastic cells. CML is associated with the fusion of BCR (on chromosome 22) and ABL1 (on chromosome 9) resulting in the BCR-ABL1 fusion gene. The translocation of chromosomes (9;22)(q34;p15) is present in almost 90-95% of patients with CML and only 5-8% CML patients have established variant complex translocation due to the participation of one or more chromosomes other than 9 and 22 chromosome. In the present study, a unique case of a pH chromosome-positive CML is reported with a new variant pH translocation involving three chromosomal aberrations 6p22, 9q34, 22q11.2 and derivation 19 which has not been described previously. The complex variant translocation with pH chromosome was 46,XY,t(6;9;22)(p22:q34;q11.2), der(19)[48]/46,XY[2]  in this newly diagnosed CML patient. Additional cytogenetic anomalies may be seen in patients which are not controlled by the tyrosine kinase inhibitor in CML patients or in accelerated/blastic phase. In this case, the patient' treatment was switched to dasatinib because the IS-NCN could not be controlled with imatinib. In conclusion, complex translocations in unusual locations of the BCR / ABL gene appear to indicate a poor prognosis.

Impact of bone marrow plasma cells percentage on survival at diagnosis and pre-transplant period in newly diagnosed multiple myeloma: Experience of a single center from Turkey.

BACKGROUND AND AIM: The current definition of complete remission (CR) in multiple myeloma (MM) includes negative serum and urine immunofixation (IFE) tests and <5% bone marrow plasma cells (BMPCs). The aim of this study was to examine the impact of BMPC percentage on survival, at diagnosis and pre-transplant period, in newly diagnosed multiple myeloma. MATERIALS AND METHODS: One hundred and fourty eight patients with newly diagnosed MM who had received autologous stem cell transplantation (ASCT) in our HSCT (hematopoietic stem cell transplant) center at Hacettepe University Hospital between the years of 2008 and 2018 were evaluated retrospectively. RESULTS: The median follow-up period was 27.4 months (range, 4.5-122) for the entire group. The 3-year OS was 87% in the pre-transplant BMPCs <5% group and 92% in the pre-transplant BMPCs ≥ 5% group, there was no statistically significant difference. The 5-year OS for the pre-transplant BMPCs <5% group and the pre-transplant BMPCs ≥ 5% group were 73% and 70%, respectively (p = 0.50). The 3-year PFS in the pre-transplant BMPCs <5% group and the pre-transplant BMPCs ≥ 5% group were 77% and 57%. The 5-year PFS in the pre-transplant BMPCs <5% group and the pre-transplant BMPCs ≥ 5% group were 43% and 13%, respectively. There was a statistically significant difference between the two groups with respect to PFS (p = 0.04). CONCLUSION: In conclusion, this study highlights the importance of reaching <5% BMPCs at pre-transplant period. OS and PFS were better in patients who had pre-transplant BMPCs <5% than pre-transplant BMPCs ≥ 5%.

Depth of invasion for appendiceal metastasis of ovarian cancers: does it have any clinical significance?

AIM: Depth of appendiceal metastasis in patients with epithelial ovarian carcinoma (EOC) has not been previously analyzed for a possible relationship with clinico-pathological variables. METHODS: Sixty-nine patients with EOC treated at Hacettepe University were retrospectively analyzed. All of the patients had appendiceal metastasis. Pathological slides were re-reviewed by the same pathologist. Appendiceal metastases were defined as serosal (if tumoral spread involved only serosa of the appendix) or sero-mucosal (if tumoral spread also involved either muscular or mucosal surfaces of the appendix). Univariate and multivariate analysis did not reveal a significant difference with respect to the prognostic variables between the groups. RESULTS: Thirty-nine patients had serosal appendiceal metastasis (56.5%), while the remaining 30 patients (43.5%) had appendiceal metastasis extending toward the muscular layer (seromucosal metastasis: 16 within muscularis mucosa, 14 within the mucosa of the appendix). The mean age at the time of diagnosis was 54.58 years (range, 26-88 years), with no significant difference between the groups (P = 0.9). Comparison of the survival rates between the two groups did not reveal a significant difference. Three-year survival rates were 23.3% in the serosal metastasis and 27.9% in the seromucosal metastasis group (P = 0.9). This figure was 25% for patients with only muscular metastasis and 41.6% for patients with appendiceal metastasis extending to the mucosal layer (P = 0.2). CONCLUSION: This is the first report to analyze the metastatic pattern of EOC on the appendix with respect to depth of invasion which could not reveal a significant difference.

Cutaneous metastases of signet cell carcinoma of the rectum without accompanying visceral involvement.

Cutaneous metastasis of rectal carcinoma is a rare event. It occurs in fewer than 4% of all patients with rectal cancer. Although skin metastasis of rectal cancer is usually detected around surgical scars or on the abdominal wall, especially in the periumbilical region, it rarely presents at other sites. The early diagnosis of skin metastases in these patients is very important because it can alter treatment. A case of signet cell carcinoma of the rectum with cutaneous metastases without accompanying visceral involvement is presented, occurring 14 months after completion of adjuvant therapy.