Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology

Pathology Laboratory Archive at the University and Hospital Trust of Modena/UNIMORE: “Disaster Recovery” frame by frame

2025-04-03T10:35:23+00:00

The archive of any Pathology laboratory contains thousand of formalin-fixed and paraffin- embedded (FFPE) blocks and, as a result, serious space and management issues are created. Different authorities (with some variabilty) indicated that 10 years from the diagnosis is a congruous time before the disposal of stored tissues. Therefore, making room is not only a choice, but a necessity. Nowadays specific operating procedures exist, fully managed by human personnel. However, despite guidelines and recommendations, some accidents can occur: such events are often without any consequence but sometimes may cause serious damage for patients. In this paper we report an unwanted event that occurred in our archive in June 2024 during the collection of FFPE blocks from the year 2004 for elimination, which could have had dramatic consequences. We then highlight that innovation and automation of Pathology archives are the key of the custody of patient samples.

Cholesterol granuloma

2025-04-03T10:42:24+00:00

Digital and computational transition in the pathology lab: when did it start?

2024-11-22T19:37:04+00:00

Inflammatory cloacogenic polyp with low grade mucinous dysplasia in orthotopic neobladder: expect the unexpected

2025-04-03T14:08:02+00:00

High-grade corded and hyalinized endometrioid carcinoma of “no specific molecular profile”: report of two cases

2025-04-03T09:04:32+00:00

High-grade corded and hyalinized endometrioid carcinoma (CHEC) is an uncommon endometrial carcinoma variant which may mimic carcinosarcoma or dedifferentiated carcinoma and has shown association with mismatch repair deficiency (MMRd) and p53 abnormalities. Herein, we expand the spectrum of high-grade CHEC by presenting two cases showing a “no specific molecular profile” (NSMP). Case #1 was a 6-cm endometrial mass in a 25-year-old woman, infiltrating the deep myometrium and cervical stroma, with diffuse lymphovascular space invasion. Case #2 was an advanced, unresectable endometrial carcinoma involving the lower third of the vagina in an 81-year-old woman. On the endometrial biopsy specimen, both cases showed a markedly atypical and mitotically active corded component merging with a FIGO G3 endometrioid component and accompanied by squamous/morular differentiation. Both tumors showed nuclear β-catenin accumulation, retained MMR protein expression, wild-type p53 pattern, and no POLE mutations.
The corded component was absent in the hysterectomy specimen of case #1 and in the vaginal biopsy specimen of case #2. The present cases confirm the clinical and molecular heterogeneity of high-grade CHEC, including a wide age range at presentation, variable prognosis, and variable molecular background. Nonetheless, these cases retain unique features that support their distinction from carcinosarcoma and dedifferentiated carcinoma. We suggest to consider them as a variant of FIGO G3 endometrioid carcinoma. Further studies are necessary in this field.

Foetal cardiac rhabdomyoma due to paternal TSC1 Mutation: a case report and literature review

2025-04-03T09:53:45+00:00

Rhabdomyomas are the most common prenatal cardiac tumours, and are often associated with tuberous sclerosis complex (TSC). They have been shown to grow during foetal development, but may often regress or shrink in early childhood.
In the present case, ultrasonography at 20+2 gestational weeks identified two echogenic masses suspicious of rhabdomyomas in the foetal heart. Neither of these tumours caused significant haemodynamic instability. Genetic testing of DNA extracted from amniocytes revealed a pathogenic variant of the TSC1 gene, supporting the diagnosis of tuberous sclerosis. The pregnancy was terminated at 21+1 weeks. Pathological examination confirmed the presence of two cardiac rhabdomyomas, histologically characterised by distinctive large vacuolated cells with central nuclei and radial cytoplasmic extensions.
Further research and a multidisciplinary approach are highly recommended to improve management and outcomes of prenatal tumours.

Lipoblastoma-like tumor of the inguinal region: a close mimicker of myxoid liposarcoma

2025-04-03T10:16:06+00:00

Lipoblastoma-like tumor is a rare mesenchymal neoplasm, typically arising in the vulvar region of young women. Although it is considered a benign tumor, rare local recurrences and exceptionally distant metastases have been reported. Histological examination reveals a well-circumscribed tumor with lobulated pattern, composed of a mixture of mature adipocytes, spindle cells and lipoblasts set in abundant myxoid stroma with numerous thin-walled capillary-like vessels. Due to the rarity of this neoplasm and its morphological resemblance with other benign and malignant lipomatous tumors, the diagnosis of lipoblastoma-like tumor is often challenging. Herein, we present a case occurring in the inguinal region of a 28-year-old woman. Histological examination showed a mixture of mature adipocytes, bland-looking spindle cells with fibrillary cytoplasm, and numerous univacuolated lipoblasts set in a prominent myxoid matrix containing numerous thin-walled branching vessels. Immunohistochemically, neoplastic cells showed diffuse immunostaining for CD34 and negativity for α-smooth muscle actin, desmin, Rb1, MDM2 and STAT6. The main differential diagnoses included myxoid liposarcoma, spindle cell lipoma and cellular angiofibroma. FISH was negative for DDIT3; moreover, no evidence of regional gain or loss of RB1 was identified by FISH. Based on morphological, immunohistochemical and cytogenetic/molecular findings, a final diagnosis of “lipoblastoma-like tumor” of the inguinal region was rendered.

Morpho-molecular approach (NGS plus digital PCR) in diagnosis of malignant biliary strictures

2025-04-03T08:39:36+00:00

Objective. To analyze the diagnostic accuracy and feasibility of digital-PCR (dPCR) combined with next-generation sequencing (NGS) in the ERCP-guided histological diagnosis of biliary strictures to overcome the issue represented by the scarcity of sampled material.
Methods. Twenty-two prospective patients were included, and submitted to ERPC-guided biopsy or biliary resection. By histopathological analysis plus fluorescence in situ hybridization (FISH) for chromosomes 3, 7, and 17 aneuploidies, 8 cases (36.4%) were malignant, and 14 cases (63.6%) were negative. NGS was performed on paraffin-embedded tissue by a laboratory-developed panel allowing the analysis of hot-spot regions in 28 genes. Digital PCR (dPCR) was performed by QuantStudio™ AbsoluteQ™ solid dPCR and the copy-number variation (CNV) of the chromosomes 3, 7, and 17 analysed.
Results. At dPCR, 1 case showed aneuploidy of chromosome 3, and 2 cases of both chromosomes 3 and 7. These 3 cases all belonged to the positive group (p = 0.014). At NGS, 6 cases showed at least one mutated gene, all in the positive group (p < 0.001). The 3 cases showing aneuploidy at dPCR also showed mutations at NGS. Basing on these observations, we can propose a diagnostic algorithm: dPCR can be applied first, allowing a diagnosis of malignancy in one working day if aneuploidies are observed. In the case of negative dPCR, a “second-line” NGS is performed on the same extracted material.
Conclusions. The implementation of dPCR allowed the identification of nearly 40% of positive cases in just one working day. In cases of negative dPCR, the NGS procedure can start on the same extracted nucleic acid used for dPCR, requiring more time, but reaching a 75% sensitivity. More studies are required to identify other more sensitive and specific dPCR targets, but even if our algorithm does not increase diagnostic accuracy, the possibility of avoiding FISH and reaching a diagnosis in a more time- and money-saving fashion might be an important step.

The invisible killer: fetal vascular malperfusion in stillbirths without macroscopic cord abnormalities

2025-04-03T08:53:15+00:00

Objective. The aim was to evaluate the association between fetal vascular malperfusion (FVM) and the umbilical cord characteristics in stillbirth. FVM is a category of placental lesions consistent with restriction/interruption of fetal blood flow, frequently associated with a “cord accident”. In some stillbirths, gross umbilical cord abnormalities unravel at birth, helping to elucidate the cause of death; however, other cases do not show any structural alterations and therefore these cases do not have an obvious cause of death.
Methods. Retrospective histopathological evaluation of singleton antepartum stillbirths affected by of FVM. Clinical and histopathological findings were compared among cases with or without gross umbilical cord abnormalities.
Results. One hundred and three cases were evaluated. Forty-eight cases (48/103; 46.6%) of stillbirth with FVM showed gross umbilical cord abnormalities, whereas 55/103 cases (53.4%) did not show any gross anomalies. Clinical risk factors for stillbirth were equally distributed between cases. Notably, the main histological lesion observed in cases without gross umbilical cord abnormalities was fatal thrombosis of the fetal vessels along the cord-placental vascular tree. This finding implies that the absence of macroscopic cord anomalies is not a sufficient criterion to exclude reduction/interruption of fetal blood flow and cord accidents as a potential cause of stillbirth.
Conclusion. Knowing the cause of fetal death is paramount both for bereaved parents and clinicians, helping in stillbirth acceptance and future prevention strategies. Our findings show the occurrence of FVM in cases without macroscopic umbilical cord anomalies. Therefore, an in-depth placental histopathological examination is mandatory to unravel signs of fetal blood flow obstruction in cases in which umbilical cord looks grossly normal. This knowledge helps parents, and health care providers in the real identification of the pathogenesis of fetal death, as the first step for personalized future actions of stillbirth prevention.

Automation in Pathology for patient safety

2025-04-03T07:57:40+00:00

The pathogenesis of idiopathic pulmonary fibrosis: from “folies à deux” to “Culprit cell Trio”

2025-04-03T08:17:17+00:00

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with poor survival affecting aging people. Although the etiology of IPF is “ufficially” considered as unknown ¹, the pathogenesis of the disease has been substantially deciphered, revealing a complex scenario where different cellular and molecular mechanisms are involved. From the early seminal proposal of Selman et al. ^2,3 a consistent amount of data have confirmed the occurrence of a deranged crosstalk of epithelial and mesenchymal cells, and this paradigm ^3-5 replaced the previous mainstream “inflammatory” theory ^6,7. The role of intrinsic defects affecting type-II pneumocytes/alveolar epithelial cells (AECII) became more precisely defined when genetic studies on familial pulmonary fibrosis (and also sporadic cases) revealed specific gene mutations interfering with the control of either telomere length or genes specifically expressed by AECII (surfactant proteins, ABCA) ^8-12. Taken together these observations suggest that the initial (etiologic) mechanism is caused by a senescence-related progressive loss of stem/precursor reparative functions of AECII ¹³. In this pathogenic scheme, the concurrent contribution of a variety of risk and noxious factors (genetic defects/predisposition, “natural” replicative senescence, and toxic substances such as cigarette smoke and pollution) may determine cell senescence and stem-cell exhaustion in predisposed areas of lung parenchyma (where high levels of mechanical stress occur) ^14-17.

The Morgagni Anatomical Theatre: 100 Years of Pathological Anatomy Education at the University of Padua (1924-2024)

2025-04-03T10:31:35+00:00

Between the 15^th and 16^th centuries, the medical school in Padua revolutionised the field of anatomy through a series of scientific discoveries and educational innovations, culminating in the construction of the world’s first stable anatomical theatre. This theatre was inaugurated in 1595 within Bo Palace by Hieronymus Fabricius (1533-1619).
The anatomical theatre was used for lectures until March 7, 1874, and the structure was preserved as a museum at the request of Giampaolo Vlacovich (1825-1899), the last anatomy professor to use it. Soon after, new theatres were built under the direction of Lodovico Brunetti (1813-1899) at the former convent of San Mattia, where many disciplines relocated to stay close to the new Giustinianeo Hospital. Subsequently, in the early 20^th century, under the leadership of Augusto Bonome (1857-1922) and Vittorio Rossi (1865-1938), the Rector of the University of Padua, it was decided to construct a new building for anatomical studies to replace the inadequate facilities at San Mattia. Construction of this ambitious project began in July 1920, starting with the autopsy room, called the Morgagni Theatre, which was completed in December 1922. Today, the theatre commissioned by Bonome just re-opened after a respectful restoration, with the aim of continuing the important educational activities in anatomical pathology as in the past.