Abdominal Lymphadenopathies: Lymphoma, Brucellosis or Tuberculosis? Multidisciplinary Approach-Case Report and Review of the Literature.

Abdominal pain represents a frequent symptom for referral to emergency departments and/or internal medicine outpatient setting. Similarly, fever, fatigue and weight loss are non-specific manifestations of disease. The present case describes the diagnostic process in a patient with abdominal pain and a palpable abdominal mass. Abdominal ultrasonography confirmed the presence of a mass in the mesogastrium. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans oriented toward calcific lymphadenopathies with increased metabolism in the positron emission tomography-computed tomography (PET-CT) scan. Laboratory examinations were inconclusive, although serology for Brucella and the Quantiferon test were positive. After multidisciplinary discussion, the patient underwent surgical excision of the abdominal mass. Histological examination excluded malignancies and oriented toward brucellosis in a patient with latent tuberculosis. The patient was treated with rifampin 600 mg qd and doxycycline 100 mg bid for 6 weeks with resolution of the symptoms. In addition, rifampin was continued for a total of 6 months in order to treat latent tuberculosis. This case underlines the need for a multidisciplinary approach in the diagnostic approach to abdominal lymphadenopathies.

Histological Features of Celiac-Disease-like Conditions Related to Immune Checkpoint Inhibitors Therapy: A Signal to Keep in Mind for Pathologists.

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1), and its ligand PDL-1, are finding increasing application in the treatment of malignant neoplasms. The widespread clinical use of these drugs, however, resulted in the discovery of side effects. The occurrence of celiac disease (CD) after ICIs therapy has been reported in the literature, but its incidence remains unknown and the role of ICIs in its onset is not yet clear. In this review, we examine the published data on this topic in order to better understand and define this entity from a histological point of view. We performed an electronic literature search to identify original reports in which CD or pathological CD-like conditions were documented histologically in patients treated with ICIs. We identified ten papers. A total of twenty-five patients were included in these publications, eleven of them receiving a serologic and histological diagnosis of CD, and four a histological diagnosis of CD-like conditions, in which pathogenesis appears to be multifactorial. ICIs can cause a CD-like enteropathy and biopsies with clinical integration are crucial to diagnose this condition. CD rarely has been observed during treatment with ICIs and its morphological aspects are similar to ICIs-CD enteropathy. Moreover, the onset of ICIs-CD may have a distinct immune mechanism compared to classical CD. Thus, the pathologists must make a histological diagnosis of CD with caution and only in adequate clinical and serological context.

Clinic, Endoscopic and Histological Features in Patients Treated with ICI Developing GI Toxicity: Some News and Reappraisal from a Mono-Institutional Experience.

Background: Immune checkpoint inhibitors (ICIs) have widened the therapeutic scenario of different solid tumors over the last ten years. Gastrointestinal (GI) adverse events (AEs), such as diarrhea and colitis, occur in up to 50% of patients treated with ICIs. Materials and methods: We conducted a single-center retrospective analysis in patients with solid tumors treated with ICIs in a 6-year period, from 2015 to 2021, developing GI AEs, for which an endoscopic analysis was performed, with available histological specimens or surgery. Results: Twenty-one patients developed GI AEs under ICIs. The median time from the start of ICIs to the onset of GI AEs was 5 months. Diarrhea was the most frequent symptom (57.2%), upper GI symptoms presented in four patients (19%), while three patients (14.3%) had no symptoms and were diagnosed occasionally. Two patients underwent surgical resection for acute abdomen. Histological findings observed in endoscopic sampling were eosinophilic-pattern gastro-enterocolitis, apoptotic damage, IBD-like features, and ischemic-like changes. Histological damage was also documented in patients with unremarkable endoscopy. Conclusions: Under ICI therapy, GI toxicity is an expected event. Since GIAEs can mimic a broad range of primary GI diseases, a multidisciplinary approach is advocated with upper and lower GI mucosal sampling to remodel therapy and avoid complications.

Intravascular NK/T-Cell Lymphoma: What We Know about This Diagnostically Challenging, Aggressive Disease.

Intravascular lymphoma is a form of lymphoid malignancy characterized by neoplastic cells growing almost exclusively within the lumina of small- to medium-sized blood vessels. Most cases are of B-cell origin with rare cases of natural killer or T-cell lineage. Extranodal sites are affected, mainly the skin and central nervous system, although any organ may be involved. Intravascular NK/T-cell lymphoma deserves special attention because of its clinicopathologic features and the need for adequate immunophenotyping combined with clonality test for a proper diagnosis. Moreover, intravascular NK/T-cell lymphoma is strongly linked to Epstein-Barr virus (EBV), which is considered to play a role in tumorigenesis and to be responsible for the aggressive behavior of the disease. In this paper, we review the current knowledge on this rare lymphoma and, in particular, the most recent advances about its molecular landscape. The main distinguishing features with other EBV-related entities, such as extranodal NK/T-cell lymphoma, EBV-positive primary nodal T/NK-cell lymphoma, and aggressive NK-cell leukemia, are discussed to help pathologists obtain the correct diagnosis and consequently develop an adequate and prompt therapy response.

Spontaneous cutaneous cholesterol crystal embolism with focal clinical symptomatology: report of a case in an unusual location with secondary histological changes reminiscent of atypical decubital fibroplasia.

Cholesterol crystal embolization (CCE) is one of the many complications of atherosclerosis. CCE is usually an iatrogenic event occurring either after vascular surgery, usually aortic surgery, or invasive angiographic investigations or in the course of anticoagulant or thrombolytic therapy. More rarely, it occurs after trauma or even in the absence of any inciting cause. CCE may manifest with single or multiorgan involvement. Skin involvement is usually seen in the context of a systemic disease, especially affecting the lower extremities and lower trunk. We report on a rare case of isolated spontaneous focal cutaneous involvement of the upper limb, with peculiar mesenchymal and reactive histological changes. A 65-year-old man with a clinical history of atherosclerosis was admitted complaining of a nonhealing painful skin ulceration on his left elbow for 5-month duration. A skin biopsy was taken, and histopathological examination documented an intrarteriolar cholesterol embolus in the dermis along with a peculiar adjacent bizarre fibroblastic reaction, of the type usually seen in atypical decubital fibroplasia of debilitated patients. The ulceration was surgically excised, and the wound was sutured and repaired. At 18-month follow-up, the patient has no evidence of local disease.

Paratesticular mesothelioma. Report of a case with comprehensive review of literature.

Paratesticular mesotheliomas are rare tumors with 223 cases described so far. The sole plausible causative factor so far ascertained in the pathogenesis of these tumors is asbestos, which however is found in only around 30% to 40% of such cases. The age range of affected individuals is wide, mostly adults and the elderly, but also includes young people and children. The most common presenting symptom is either hydrocele of unknown origin or intrascrotal mass. When hydrocele is the presenting symptom, these tumors are often clinically overlooked and the diagnosis is delayed. Most paratesticular mesotheliomas arise in the tunica vaginalis, but primary tumors of the spermatic cord and epididymis are also on record. Tumors arising from the peritoneal mesothelium of a hernia sac are excluded from this group. The correct diagnosis is almost always made after histologic examination of the operative specimen. Immunohistochemistry and electron microscopy are always helpful and sometimes necessary tools for diagnosis. So far very few cases have been identified or suspected preoperatively on cytologic examination. Three clinicopathologic types of malignant mesotheliomas of the male genital tract are recognized: diffuse tubulo-papillary mesothelioma, well-differentiated papillary mesothelioma, and multicystic mesothelioma. The histologic subtypes are almost always pure epithelial or biphasic. The differential diagnosis is mainly with serous papillary tumors arising from Mullerian vestiges, but several diverse primary or secondary tumors also need to be considered. A clinicopathologic evaluation of a case of tunical diffuse mesothelioma in a 74-year-old male from the AMR Series is the starting point for this general review.

Primary effusion lymphoma metachronous to multicentric Castleman disease in an immunocompetent patient.

Human Herpesvirus 8 (HHV8) has been associated with a wide spectrum of B-cell lymphoproliferative disorders, including Primary Effusion Lymphoma, Multicentric Castleman Disease, HHV8-positive Diffuse Large B-cell Lymphoma, not otherwise specified and germinotropic lymphoproliferative disorder. The association of different HHV8-related lymphoproliferative disorders is described in immunodeficient patients. We report a case of Primary Effusion Lymphoma metachronous to Multicentric Castleman Disease in an immunocompetent patient.

Diagnosis of Hodgkin Lymphoma from Cell Block: A Reliable and Helpful Tool in "Selected" Diagnostic Practice.

BACKGROUND: The diagnosis of lymphoma requires surgical specimens to perform morphological evaluation, immunohistochemical and molecular analyses. Ultrasound-guided fine needle aspiration may represent an appropriate first approach to obtain cytological samples in impalpable lesions and/or in patients unsuitable for surgical procedures. Although cytology has intrinsic limitations, the cell block method may increase the possibility of achieving an accurate diagnosis. METHODS: We retrospectively selected a total of 47 ultrasound-guided fine needle aspiration and drainage samples taken from patients with effusion and deep-seated lesions which are clinically suspicious in terms of malignancy. RESULTS: In 27 cases, both cell block and conventional cytology were performed: 21/27 cell blocks were adequate for the diagnosis of lymphoma and suitable for immunocytochemistry and molecular analyses vs. 12/20 samples to which only conventional cytology was applied. Moreover, in five patients we were able to make a diagnosis of Hodgkin lymphoma with the cell block (CB) technique. CONCLUSIONS: Contrary to conventional cytology, the cell block method may allow immunocytochemistry and molecular studies providing useful information for the diagnosis and subtypization of lymphoma in patients unsuitable for surgical procedure or with deep-seated lesions or extra-nodal diseases; additionally, it is a daily, simple and helpful approach. Moreover, we describe the usefulness of cell blocks in the diagnosis of Hodgkin lymphoma.

Cystic lymphangioma-like adenomatoid tumor of the adrenal gland: Case presentation and review of the literature.

Adenomatoid tumors (AT) are usually found in the genital tract of both sexes. They are very rarely located in extragenital sites, and are exceedingly rare in the adrenal. AT of the adrenal gland (AT-AG) are nonfunctioning, usually discovered incidentally and confused on imaging with other more common adrenal neoplasms. The overwhelming majority occur in males. Thirty-four cases have been reported so far, more often presenting grossly as solid tumors, rarely as solid with cystic areas, and 5 cases were almost entirely cystic. At histology they can be either circumscribed or locally infiltrative, and may pose diagnostic difficulties when the pathologist relies on morphology alone or is challenged on frozen section. On light microscopy the diagnosis may be very difficult if the tumor is rich in vacuolated cells, mimicking metastatic signet ring-cell adenocarcinoma. Immunophenotyping and/or electron microscopy are paramount in helping to ascertain their mesothelial lineage. Lymphangioma is the main histologic mimic of solid-cystic and cystic AT-AG, but lymphangioma is immunopositive for endothelial markers and negative for cytokeratins and mesothelial markers. Ultrastructural analysis has been performed in 10 published cases of AT-AG, in all of which the classical microvilli of coelomic type were always observed. In brief we report herein the sixth case of cystic lymphangioma-like AT, which was incidentally discovered during clinical follow-up in a 39-year-old man undergoing cancer staging and surveillance after surgery. The adrenal tumor was 5.5 cm in size and was fully investigated immunohistochemically and ultrastructurally. A complete review of the literature is also presented.

Tuberous sclerosis complex with polycystic kidney disease of the adult type: the TSC2/ADPKD1 contiguous gene syndrome.

Although different diseases, tuberous sclerosis complex and autosomal dominant polycystic kidney disease have been seen in association, the molecular basis of this being the proximity of tuberous sclerosis complex 2 and polycystic kidney disease 1 genes on the same chromosome (16p13.3). Therefore, the classic autosomal dominant polycystic kidney disease renal phenotype may occur in the context of tuberous sclerosis complex disease as a result of large deletions involving both the polycystic kidney disease 1 and tuberous sclerosis complex 2 genes. This is known as the tuberous sclerosis complex 2/autosomal dominant polycystic kidney disease 1 contiguous gene syndrome. The criteria for this condition are fulfilled when renal lesions typical for classic autosomal dominant polycystic kidney disease phenotype are associated with tuberous sclerosis complex phenotype. We present a new case of the sporadic form of this genetic disorder. The diagnosis of tuberous sclerosis complex in this patient was established on the presence of major and minor features, and the diagnosis of ADPKD was based on the presence of numerous large roundish renal cysts lined by a nondescript tubular epithelium. Sporadic cases of autosomal dominant polycystic kidney disease and tuberous sclerosis complex do occur. Molecular analysis was not performed because the patient's parents refused permission.

[Encrusted Pyelitis during a case of Thrombotic Thrombocytopenic Purpura].

Encrusted pyelitis is a chronic urinary tract infection associated with mucosal encrustation induced by urea splitting bacteria. More than 40 bacteria have been implicated but the most frequent is Corynebacterium group D2. Predisposing factors are debilitating chronic diseases and preexisting urological procedures. Immunosoppression is an important cofactor. For these reasons the disease is almost always nosocomially acquired and renal transplant recipients are at particular risk. The symptoms are not specific and long lasting: dysuria, flank pain and gross haematuria are the most frequent; fever is present in two-thirds. The demonstration of urine splitting bacteria in constantly alkaline urines and radiological evidence of extensive calcification of pelvicalyceal system, ureter and bladder at US or CT scan in a clinical context of predisposing factors are the mainstay of diagnosis. Treatment is based on adapted antibiotic therapy, acidification of urine and excision of plaques of calcified encrustation. The prognosis relies on timing of diagnosis; delay can be detrimental and result in patient's death and graft loss. We describe a unique case of 69-year-old man with two contemporary diseases: autoimmune thrombotic thrombocytopenic purpura and encrusted pyelitis with a fatal evolution.

Exogenous Lipoid Pneumonia due to Chronic Inhalation of Oily Product Used as a Lubricant of Tracheotomy Cannula.

Exogenous lipoid pneumonia (ELP) is caused by the inhalation of vaporized oily products. Long-term exposure can result in chronic disease, whereas acute form usually results from massive aspiration of fatty substances. It has an incidence of 1.0%-2.5%. In case of symptomatic patients, the clinical presentation mainly includes acute or chronic respiratory symptoms such as dyspnea, fever, cough and less frequently chest pain, hemoptysis, or weight loss. Radiological findings are often aspecific or misinterpreted, and ELP is sometimes misdiagnosed as a malignancy of the lungs. Patient history and radiological findings can lead to a suspicion of ELP, but histological microscopic findings of intra-alveolar lipid and lipid-laden macrophages are required to confirm the diagnosis The mainstay of treatment consists of avoiding ongoing exposure and providing supportive care as repeated whole-lung lavage, corticosteroids, and/or immunoglobulins. Surgery is reserved for cases of high suspicion of cancer or serious clinical impact (as recurrent infections). Prognosis is benign, even if it has been reported cases of progression to severe respiratory failure, cor pulmonale, superinfection, and association with lung cancer. Here, we describe a case of ELP due to chronic inhalation of oily product (Vaseline) used as a lubricant of tracheotomy cannula.

Primary embryonal rhabdomyosarcoma of the prostate in adults: report of a case and review of the literature.

This study reports on a case of an adult patient with embryonal rhabdomyosarcoma of the prostate and comprehensively reviews the world literature on this subject. The patient was a 49-year-old man with advanced stage disease, who initially underwent transurethral tumor resection and after diagnosis was given courses of chemotherapy prior to undergoing radical cystoprostatevesiculectomy. The tumor underwent histological examination supplemented by immunohistochemical analysis. After surgery, the patient experienced a huge pelvic recurrence and eventually died of disease 1 year after the original diagnosis. The world literature was reviewed based both on a PubMed/Medline search and the reference lists of all the available publications on this subject and only 24 cases of primary embryonal prostatic rhabdomyosarcoma have been found in the world literature in adult males (≥ 18 years). Embryonal rhabdomyosarcoma of the prostate in adults is a very rare and aggressive disease. The long-term disease-specific survival rate is poor. Stage influences the outcome. Early diagnosis and complete surgical resection offer patients the best chance of improved survival.

Lipofuscin-like granules of the juxtaglomerular apparatus of the kidney. The diagnostic significance of a quasi-normal subcellular structure incidentally encountered in the course of routine ultrastructural evaluation of renal biopsies.

Lipofuscin-like granules, first described by Biava and West in 1965, are a subcellular, quasi-physiologic finding mainly seen in the smooth muscle cells of renal arterioles, but also in juxtaglomerular cells and the lacis cells of human kidneys. They increase in number in subjects affected by arterial hypertension and diabetes. They do not correlate with a specific primary renal disease. Lipofuscin-like granules are not related to renin granules. The world literature on this subject is almost non-existent, and the awareness of this finding or its clinical significance among either pathologists or nephrologists is very poor. We incidentally observed these lipofuscin-like granules in 8 cases during the routine electron microscope examination of 440 renal biopsies, and report herein on their ultrastructural features. Six of these 8 patients were affected by arterial hypertension, one of whom was also concomitantly affected by diabetes mellitus. These lipofuscin-like granules appear as dense bodies with a lipid component, a coarsely granular matrix, and a crystalloid component which may appear in a band or dot pattern, according to the plane of sectioning. The pathologist has to be aware of these lipofuscin-like granules in order not to confuse them with the semicircularly organized (fingerprint) linear immune deposits associated with some specific glomerulopathies.

Changes in CpG islands promoter methylation patterns during ductal breast carcinoma progression.

Aberrant promoter methylation of several known or putative tumor suppressor genes occurs frequently during carcinogenesis, and this epigenetic change has been considered as a potential molecular marker for cancer. We examined the methylation status of nine genes (APC, CDH1, CTNNB1, TIMP3, ESR1, GSTP1, MGMT, THBS1, and TMS1), by quantitative methylation specific PCR. Synchronous preinvasive lesions (atypical ductal hyperplasia and/or ductal carcinoma in situ) and invasive ductal breast carcinoma from 52 patients, together with pure lesions from 24 patients and 12 normal tissues paired to tumor and 20 normal breast distant from tumor were analyzed. Aberrant promoter methylation was detected in both preinvasive and invasive lesions for genes APC, CDH1, CTNNB1, TIMP3, ESR1, and GSTP1. However, hierarchical mixed model and Generalized Estimating Equations model analyses showed that only APC, CDH1, and CTNNB1 promoter regions showed a higher frequency and methylation levels in pathologic samples when compared with normal breast. Whereas APC and CTNNB1 did not show differences in methylation levels or frequencies, CDH1 showed higher methylation levels in invasive tumors as compared with preinvasive lesions (P < 0.04, Mann-Whitney test with permutation correction). The analysis of APC, CDH1, and CTNNB1 methylation status was able to distinguish between normal and pathologic samples with a sensitivity of 67% (95% confidence interval, 60-71%) and a specificity of 75% (95% confidence interval, 69-81%). Our data point to the direct involvement of APC, CDH1, and CTNNB1 promoter methylation in the early stages of breast cancer progression and suggest that they may represent a useful tool for the detection of tumor cells in clinical specimens.

Lateral ventricle tumors: surgical strategies according to tumor origin and development--a series of 72 cases.

OBJECTIVE: Optimal surgical management in lateral ventricle tumors remains controversial. We conducted a retrospective study of patients with these lesions treated with a surgical strategy on the basis of tumor origin: primary or secondary ventricular and associated transependymal development. METHODS: A total of 72 patients underwent surgery for lateral ventricle tumors. The mean patient age was 39 years (range, 6 mo to 78 yr). Raised intracranial pressure occurred in 53% of patients, followed by mental disturbances or psychiatric symptoms (32%) and motor deficits (21%). The transcortical approach was used in 44 patients, and an interhemispheric approach was used in 28 patients; a transcallosal approach was used in 16 patients, and a parasplenial approach was used in 12 patients. Neuropsychological tests were performed in selected patients. RESULTS: Total resection was performed in 82% of patients. Sixty-five percent of tumors were benign and low-grade tumors. There was no surgical mortality, and the morbidity rate was 11%. Postoperative epilepsy (5.9%) was significantly increased in the transcortical group. The mean follow-up period was 55 months; 59% of patients achieved good recovery and moderate disability. In postoperative neuropsychological testing sessions, deficits in verbal memory were observed in six patients (8%). Final morbidity correlated well with preoperative clinical condition and pathological diagnosis. CONCLUSION: Lateral ventricle tumors can be treated best by careful selection of the approach according to tumor origin and development. Overall, the transcallosal approach is preferred, but in patients with transependymal growth or large primary or secondary ventricular tumors, the transcortical is a better option.

Lateral ventricle tumors: surgical strategies according to tumor origin and development--a series of 72 cases.

OBJECTIVE: Optimal surgical management in lateral ventricle tumors remains controversial. We conducted a retrospective study of patients with these lesions treated with a surgical strategy on the basis of tumor origin: primary or secondary ventricular and associated transependymal development. METHODS: A total of 72 patients underwent surgery for lateral ventricle tumors. The mean patient age was 39 years (range, 6 mo to 78 yr). Raised intracranial pressure occurred in 53% of patients, followed by mental disturbances or psychiatric symptoms (32%) and motor deficits (21%). The transcortical approach was used in 44 patients, and an interhemispheric approach was used in 28 patients; a transcallosal approach was used in 16 patients, and a parasplenial approach was used in 12 patients. Neuropsychological tests were performed in selected patients. RESULTS: Total resection was performed in 82% of patients. Sixty-five percent of tumors were benign and low-grade tumors. There was no surgical mortality, and the morbidity rate was 11%. Postoperative epilepsy (5.9%) was significantly increased in the transcortical group. The mean follow-up period was 55 months; 59% of patients achieved good recovery and moderate disability. In postoperative neuropsychological testing sessions, deficits in verbal memory were observed in six patients (8%). Final morbidity correlated well with preoperative clinical condition and pathological diagnosis. CONCLUSION: Lateral ventricle tumors can be treated best by careful selection of the approach according to tumor origin and development. Overall, the transcallosal approach is preferred, but in patients with transependymal growth or large primary or secondary ventricular tumors, the transcortical is a better option.