Assessing Response to PSMA Radiopharmaceutical Therapies with Single SPECT Imaging at 24 Hours After Injection.

Understanding the relationship between lesion-absorbed dose and tumor response in 177Lu-PSMA-617 radiopharmaceutical therapies (RPTs) remains complex. We aimed to investigate whether baseline lesion-absorbed dose can predict lesion-based responses and to explore the connection between lesion-absorbed dose and prostate-specific antigen (PSA) response. Methods: In this retrospective study, we evaluated 50 patients with 335 index lesions undergoing 177Lu-PSMA-617 RPT, who had dosimetry analysis performed on SPECT/CT at 24 h after cycles 1 and 2. First, we identified the index lesions for each patient and measured the lesion-based absorbed doses. Lesion-based response was calculated after cycle 2. Additionally, PSA50 response (a decline of 50% from baseline PSA) after cycle 2 was also calculated. The respective responses for mean and maximum absorbed doses and prostate-specific membrane antigen (PSMA) volumetric intensity product (VIP-PSMA) at cycles 1 and 2 were termed SPECTmean, SPECTmaximum, and SPECTVIP-PSMA, respectively. Results: Of the 50 patients reviewed, 46% achieved a PSA50 response after cycle 2. Of the 335 index lesions, 58% were osseous, 32% were lymph nodes, and 10% were soft-tissue metastatic lesions. The SPECT lesion-based responses were higher in PSA responders than in nonresponders (SPECTmean response of 46.8% ± 26.1% vs. 26.2% ± 24.5%, P = 0.007; SPECTmaximum response of 45% ± 25.1% vs. 19% ± 27.0%, P = 0.001; SPECTVIP-PSMA response of 49.2% ± 30.3% vs. 14% ± 34.7%, P = 0.0005). An association was observed between PSA response and SPECTVIP-PSMA response (R 2 = 0.40 and P < 0.0001). A limited relationship was found between baseline absorbed dose measured with a 24-h single time point and SPECT lesion-based response (R 2 = 0.05, P = 0.001, and R 2 = 0.03, P = 0.007, for mean and maximum absorbed doses, respectively). Conclusion: In this retrospective study, quantitative lesion-based response correlated with patient-level PSA response. We observed a limited relationship between baseline absorbed dose and lesion-based responses. Most of the variance in response remains unexplained solely by baseline absorbed dose. Establishment of a dose-response relationship in RPT with a single time point at 24 h presented some limitations.

Actinium-225 targeted alpha particle therapy for prostate cancer.

Targeted alpha particle therapy (TAT) has emerged as a promising strategy for the treatment of prostate cancer (PCa). Actinium-225 (225Ac), a potent alpha-emitting radionuclide, may be incorporated into targeting vectors, causing robust and in some cases sustained antitumor responses. The development of radiolabeling techniques involving EDTA, DOTA, DOTPA, and Macropa chelators has laid the groundwork for advancements in this field. At the forefront of clinical trials with 225Ac in PCa are PSMA-targeted TAT agents, notably [225Ac]Ac-PSMA-617, [225Ac]Ac-PSMA-I&T and [225Ac]Ac-J591. Ongoing investigations spotlight [225Ac]Ac-hu11B6, [225Ac]Ac-YS5, and [225Ac]Ac-SibuDAB, targeting hK2, CD46, and PSMA, respectively. Despite these efforts, hurdles in 225Ac production, daughter redistribution, and a lack of suitable imaging techniques hinder the development of TAT. To address these challenges and additional advantages, researchers are exploring alpha-emitting isotopes including 227Th, 223Ra, 211At, 213Bi, 212Pb or 149Tb, providing viable alternatives for TAT.

68Ga-FAP-2286 PET of Solid Tumors: Biodistribution, Dosimetry, and Comparison with 18F-FDG.

Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of 68Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with 18F-FDG and FAPI compounds. Methods: Patients were administered 219 ± 43 MBq of 68Ga-FAP-2286 and scanned after 60 min. Uptake was measured in up to 5 lesions per patient and within the kidneys, spleen, liver, and mediastinum (blood pool). Absorbed doses were evaluated using MIM Encore and OLINDA/EXM version 1.1 using the International Commission on Radiological Protection publication 103 tissue weighting factor. Results: Forty-six patients were imaged with 68Ga-FAP-2286 PET. The highest average uptake was seen in sarcoma, cholangiocarcinoma, and colon cancer. The lowest uptake was found in lung cancer and testicular cancer. The average SUVmax was significantly higher on 68Ga-FAP-2286 PET than on 18F-FDG PET in cholangiocarcinoma (18.2 ± 6.4 vs. 9.1 ± 5.0, P = 0.007), breast cancer (11.1 ± 6.8 vs. 4.1 ± 2.2, P < 0.001), colon cancer (13.8 ± 2.2 vs. 7.6 ± 1.7, P = 0.001), hepatocellular carcinoma (9.3 ± 3.5 vs. 4.7 ± 1.3, P = 0.01), head and neck cancer (11.3 ± 3.5 vs. 7.6 ± 5.5, P = 0.04), and pancreatic adenocarcinoma (7.4 ± 1.8 vs. 3.7 ± 1.0, P = 0.01). The total-body effective dose was estimated at 1.16E-02 mSv/MBq, with the greatest absorbed organ dose in the urinary bladder wall (9.98E-02 mGy/MBq). Conclusion: 68Ga-FAP-2286 biodistribution, dosimetry, and tumor uptake were similar to those of previously reported FAPI compounds. Additionally,68Ga-FAP-2286 PET had consistently higher uptake than 18F-FDG PET. These results are especially promising in the setting of small-volume disease and differentiating tumor from inflammatory uptake.

The Impact of Posttreatment Imaging in Peptide Receptor Radionuclide Therapy.

Posttreatment imaging of γ-emissions after peptide receptor radionuclide therapy (PRRT) can be used to perform quantitative dosimetry as well as assessment response using qualitative measures. We aimed to assess the impact of qualitative posttreatment imaging on the management of patients undergoing PRRT. Methods: In this retrospective study, we evaluated 100 patients with advanced well-differentiated neuroendocrine tumors undergoing PRRT, who had posttreatment SPECT/CT imaging at 24 h. First, we evaluated the qualitative assessment of response at each cycle. Then using a chart review, we determined the impact on management from the posttreatment imaging. The changes in management were categorized as major or minor, and the cycles at which these changes occurred were noted. Additionally, tumor grade was also evaluated. Results: Of the 100 sequential patients reviewed, most (80% after cycle 2, 79% after cycle 3, and 73% after cycle 4) showed qualitatively stable disease during PRRT. Management changes were observed in 27% (n = 27) of patients; 78% of those (n = 21) were major, and 30% (n = 9) were minor. Most treatment changes occurred after cycle 2 (33% major, 67% minor) and cycle 3 (62% major, 33% minor). Higher tumor grade correlated with increased rate of changes in management (P = 0.006). Conclusion: In this retrospective study, qualitative analysis of posttreatment SPECT/CT imaging informed changes in management in 27% of patients. Patients with higher-grade tumors had a higher rate of change in management, and most of the management changes occurred after cycles 2 and 3. Incorporating posttreatment imaging into standard PRRT workflows could potentially enhance patient management.

Real-World Experience with 177Lu-PSMA-617 Radioligand Therapy After Food and Drug Administration Approval.

We report our initial real-world experience with 177Lu-PSMA-617 radioligand therapy. Methods: We performed a retrospective review of patients treated with 177Lu-PSMA-617. Pretreatment PSMA PET, laboratory findings, overall survival, a fall in prostate-specific antigen by 50% (PSA50), and toxicities were evaluated. Results: Ninety-nine patients were included. Sixty patients achieved a PSA50. Seven of 18 (39%) patients who did not meet the TheraP PSMA imaging criteria achieved a PSA50. Nineteen of 31 (61%) patients who did not meet the VISION laboratory criteria achieved a PSA50. Sixty-three patients had a delay or stoppage in therapy, which was due to a good response in 19 patients and progressive disease in 14 patients. Of 10 patients with a good response who restarted treatment, 9 subsequently achieved a PSA50 on retreatment. The most common toxicities were anemia (33%) and thrombocytopenia (21%). Conclusion: At our center, patients who did not meet the TheraP PSMA imaging criteria or the VISION laboratory criteria benefited from 177Lu-PSMA-617 radioligand therapy.

Utility of Fine Needle Aspiration in Diagnosis of Intraoral Minor Salivary Gland Tumors.

OBJECTIVE: To evaluate the utility of intraoral fine-needle aspiration cytology (FNAC) in diagnosis of minor salivary gland neoplasms (MSGN) with application of Milan system of reporting salivary gland cytopathology; keeping histopathology as gold standard and to detail the cytological findings of MSGNs. METHOD: Retrospective study between Jan 2008 and June 2017 (appro × 10 years) on the cytology of the minor salivary gland tumor along with the histopathological correlation. The relevant clinical data was collected from the medical record. RESULT: Sixty-four cases of MSGNs were included in the study. The histodiagnosis of the 41 were available. Twenty-one cases were diagnosed as malignant, while rest 20 cases were reported as benign. The most common tumor diagnosed was pleomorphic adenoma (PA) (50% cases), followed by mucoepidermoid carcinoma (14%) and adenoid cystic carcinoma (12.5%). The most common site of MSGT was found to be hard palate (44%), followed by soft palate (23%), floor of the mouth (12%), lip (11%), buccal mucosa (5%), and tongue (5%) with no gender predilection. Sensitivity of FNAC for detection of malignancy was 81% while specificity 95%. For malignancies, positive predictive value for malignancies was 17/18 (94.4%) and negative predictive value was 19/23 (82.3%). According to Milan system out of 21 cases in category IV B, 4 cases were found malignant (Category VI), while 1/18 case in category VI turned out to be nonneoplastic lesion (Category II). CONCLUSION: FNAC is imperative in early diagnosis and subsequent management of MSGNs.

Cytological evaluation of pericardial fluids: A 5 years experience in tertiary care center.

BACKGROUND: Cytological examination of pericardial effusion fluids is important in diagnosing the etiology of underlying disease, staging, and prognosis of cancer. AIMS AND OBJECTIVES: (1) To study cytological evaluation of pericardial effusions in various pathological conditions in a tertiary care center. (2) To analyze their frequency and clincopathological correlation of the diagnosis. MATERIALS AND METHODS: Our study was a retrospective study performed in the Department of Pathology from 1st January 2012 to 31st December 2016. The study sample included all the pericardial effusions submitted in the pathology department for cytological evaluation. Clinical details and relevant parameters correlated with clinical findings. Each fluid underwent cytospin and cytocentrifuge along with preparation of conventional smears. RESULTS: Of 120 cases, 80% were of benign effusion and 20% were of malignant effusion. Male-to-female ratio was 1.44:1 with patient age ranging from 3 to 90 years. CONCLUSION: Benign effusions can been seen in younger age group and malignant ones in the older age group. The preliminary pericardial fluid analysis in resource-limited settings is the most convenient and cost-effective method for accurate diagnosis. It reduces the demand of invasive investigations and its complications. At times, it is the first test to point toward underlying malignant process thereby affecting the prognosis, survival, and treatment outcome of the patient.

Xylene-free staining: Is it possible and practical?

Good paraffin sections are key to correct histopathological diagnosis. Xylene is hazardous to health, expensive, and difficult to dispose. Various substitutes have been tried without success. We aimed to examine if 1.7% dishwasher soap (DWS) aqueous solution and refined mineral oil (RMO) for deparaffinization can replace xylene. Fifty tissue blocks consisting of benign and malignant lesions were processed using xylene (A), 1.7% DWS (B), and RMO (C). Each section was evaluated, scored as 0 (inadequate) and 1 (adequate) by two independent pathologists who were blinded to agent used. Following criteria were considered: nuclear staining, cytoplasmic staining, clarity, crispness, and uniformity. Total score of <2 was graded as inadequate for diagnosis and 3-5 as adequate. Statistical analysis was done using the SPSS software by applying chi-square test. Among three methods, B had the best scores in adequacy for cytoplasmic staining (P = 0.001), clarity (P = 0.004), and crispness (P = 0.003). About 1.7% DWS and RMO were found to be effective methods for deparaffinization and can replace xylene.

A rare case of disseminated penicilliosis - first of its kind from North India.

Penicilliosis is a rare opportunistic fungal infection caused by Talaromyces marneffei, especially in the HIV-infected patients. The untreated disease is highly fatal. The infection is endemic in Southeast Asia and Northeast India. The present case is the first case of disseminated penicilliosis from North India and Delhi in a 31-year-old male, recently diagnosed with HIV. This case highlights the importance of considering an unusual organism as the cause of disseminated disease in the nonendemic area.

Extensive trophoblastic differentiation in case of an endometrial carcinoma.

Trophoblastic differentiation of endometrial carcinoma is extremely rare, till date 18 cases reports are there in the literature. A 68-year-old postmenopausal female presented with abnormal vaginal bleeding. Histopathologically, there were areas of serous carcinoma with trophoblastic differentiation (~90%). On immunohistochemistry, the trophoblastic component was positive for ß-human chorionic gonadotropin (hCG), HPL and EMA. IHC confirmed the diagnosis of serous carcinoma with trophoblastic differentiation. The clinicopathological features of 18 previously reported cases of trophoblastic differentiation in the uterine tumor were analyzed in addition to the present case.

Recurrent Dermatofibrosarcoma Protuberans with Pigmentation and Myoid Differentiation.

Dermatofibrosarcomas protuberans (DFSP) are rare low-grade tumours with various subtypes and usually occur among middle-aged adults. However, myoid differentiation is very rare. We report a 44-year-old woman who presented to the Lok Nayak Jai Prakash Hospital, New Delhi, India, in 2017 with a recurrent pigmented DFSP presenting as an arm swelling. Upon histological and immunohistochemical analysis, myoid differentiation was confirmed. A literature review of the clinical and histopathological features of this rare entity is presented.

Primary Plasma Cell Leukaemia: Case report and review of the literature.

Plasma cell leukaemia (PCL) is one of the most aggressive and rarest forms of plasma cell dyscrasia. However, the diagnostic criteria for this condition have not yet been revised and there is no specific treatment to significantly improve the course of the disease. We report a 69-year-old male who presented to the Lok Nayak Hospital, New Delhi, India, in 2017 with dyspnoea and chest pain. A peripheral blood smear showed an absolute plasma cell count of 2.16 × 109/L. A bone marrow examination showed 61% atypical plasma cells exhibiting kappa light chain restriction. Biochemical investigations were consistent with a diagnosis of primary PCL with renal involvement. Bortezomib-based chemotherapy was initiated, which resulted in an improvement in the patient's haematological and biochemical parameters. This case report includes a comprehensive review of the clinical and diagnostic features, pathobiology and treatment of PCL.

Sacrococcygeal Teratoma in a Seven-Day-Old Child with Pulmonary Differentiation.

Sacrococcygeal Teratoma (SCT) showing pulmonary differentiation has been rarely reported in the literature. Till date, only eight cases have been reported, out of which six belong to teratomas arising from female genital tract. Spinal teratomas showing pulmonary differentiation are rarer and only two cases have been reported so far in the literature both of which had associated congenital spinal anomaly. We present a rare case of seven day old infant with sacrococcygeal teratoma showing mature lung differentiation as one of its components. The infant was otherwise asymptomatic and had no associated spinal anomaly. This case has been presented for its rarity. Extensive review of the literature along with the possible pathogenesis is also included for better understanding.

Struma Ovarii with Pseudo-Meigs' Syndrome and Raised Cancer Antigen-125 Levels Masquerading as an Ovarian Carcinoma Case report and literature review.

The monodermal teratoma struma ovarii is a rare ovarian tumour; however, struma ovarii presenting with pseudo-Meigs' syndrome and raised cancer antigen (CA)-125 levels is even rarer. In elderly patients, this presentation can potentially lead to a misdiagnosis of a malignant ovarian carcinoma, resulting in unnecessary extensive surgery. We report a 55-year-old female who presented to the Lok Nayak Jai Prakash Narayan Hospital, New Delhi, India, in 2016 with progressive abdominal discomfort, fatigue and abdominal distention. Clinical and radiological features were indicative of a malignant ovarian tumour and ascites. Serum CA-125 levels were elevated at 258 U/mL. A left-sided salpingo-oophorectomy was performed, after which the serum CA-125 levels normalised. There was no evidence of recurrence at a six-month follow-up. A frozen section procedure confirmed the diagnosis of a struma ovarii. This rare condition should be considered as a differential diagnosis in patients presenting with ovarian masses, ascites and raised CA-125 levels.

Phaeohyphomycosis breast masquerading as fibroadenoma in a young teenage girl.

Phaeohyphomycosis is an unusual granulomatous fungal infection, observed in immunocompromised or diabetic patients; however, it is even rarer in immunocompetent patients. Cytological findings of the same have been infrequently reported. The histopathological diagnosis or fungal culture helps in definitive diagnosis to identify the exact fungal species. Hereby, we report a rare case of invasive fungal infection in a breast lump in a young female, presenting as fibroadenoma breast. Fine needle aspiration cytology from the breast lesion showed the presence of septate acute-angled branching fungal hyphae with focal pigmentation, morphologically suggestive of phaeohyphomycosis which was positive with fungal stains. This was later confirmed on biopsy as histopathology slides showed the presence of prominent pigmented fungal hyphae. The pus culture from needle aspirate also showed phaeohyphomycotic fungal organism delineating the species Exophiala dermatitidis. Aspiration cytology is crucial for the diagnosis of fungal infection in such cases. An appropriate diagnosis will help in early detection and treatment of such infections as these are usually associated with high morbidity and mortality.

Broad Ligament Lipoleiomyoma Masses: Two curious cases masquerading as ovarian carcinomas.

Lipoleiomyomas are an extremely rare form of uterine leiomyoma; moreover, the occurrence of this type of tumour on the broad ligament is even rarer. We report two cases of broad ligament lipoleiomyomas in 15- and 38-year-old female patients who presented to the Lok Nayak Jai Prakash Hospital in New Delhi, India, between 2016 and 2017. In both cases, the preoperative diagnosis was of a solid ovarian malignancy. Most broad ligament tumours are mistaken for ovarian masses as they are difficult to diagnose radiologically.

Juvenile Xanthogranuloma in Vulva of a 10-Year-Old Child.

A 10-year-old child presented with asymptomatic, well-circumscribed nodule in the vulva. Excision biopsy showed features of classic Juvenile Xanthogranuloma (JXG) which is a rare benign disorder of non-langerhans' cell group of histiocytic proliferative diseases. The presentation of this lesion as vulval nodule is extremely rare and the extensive literature search revealed only handful of cases of vulval xanthogranuloma that too in an adult age group. The lesion is however prognostically favourable and should be kept in mind as one of the differential diagnosis of the vulval nodule.