Primary peritoneal low-grade serous carcinoma detected in cervical smear: Pitfalls mitigated by clinicocytopathologic clues and cellblock immunocytochemistry.

Pap smears play a role in detecting extrauterine serous tumours in asymptomatic women. Certain cytopathologic and histopathologic findings combined with relevant clinical and radiologic findings indicate the possibility of primary peritoneal serous tumours. Cellblock immunohistochemistry is a valuable confirmatory diagnostic tool.

Concomitant Tuberculous and Lepromatous Lymphadenitis: Clues and Pitfalls of Leprosy Concealed by Tuberculosis in Lymph Nodes.

Comorbidities between tuberculosis and leprosy are expected in endemic regions. Pulmonary tuberculosis and cutaneous leprosy are the most prevalent coinfections. One of the common manifestations of tuberculosis is generalized lymphadenopathy. In contrast, leprosy is clinically less suspected to manifest as a generalized lymphadenopathy, and it is pathologically unusual to diagnose leprosy primarily in lymph nodes. Concomitant tuberculous and lepromatous lymphadenitis are unprecedented and clinically unexpected, particularly in nonendemic countries. This imposes diagnostic challenges. We report concurrent tuberculosis and leprosy that were diagnosed in a lymph node in 45-year-old man with generalized lymphadenopathy. The effaced lymph node was predominantly replaced by caseating epithelioid granulomas alternating with foamy histiocytes. Ziehl-Neelsen stain showed positive acid-fast bacilli in the necrotizing granulomas only. The initial differential diagnosis of the nodal foamy macrophages included fungal infections, leishmaniasis, and Whipple disease, for which the special stains were negative. The vacuolated macrophages were disregarded as nonspecific lipogranuloma. A modified acid-fast stain was not considered. The histopathologic clues to nodal lepromatous leprosy included the presence of intracytoplasmic globi, intermixed microabscesses, and lymphoplasmacytic infiltrate and involved pericapsular nerves. Wade-Fite stain was subsequently performed. It revealed numerous lepra bacilli within the foamy histiocytes. The final diagnosis was concurrent disseminated tuberculosis and leprosy. Nodal lepromatous leprosy could be missed when compounded by concurrent nodal tuberculosis, particularly in developed countries. The clinicians and pathologists should have a high index of suspicion, particularly in patients from or with history of travel from endemic regions. Certain histopathologic features are helpful clues to avoid pitfalls.

Nevus lipomatosus superficialis: A series of six cases.

Nevus lipomatosus still imposes diagnostic, categorization, and etiologic challenges. Even though an intradermal adipose tissue is a histopathologic prerequisite, the lesions are clinically divided into classic multiple forms and a solitary variant, which some consider a separate so-called lipofibroma clinicopathologic entity. This further complicates the true prevalence, classification and etiopathogenesis of nevus lipomatosus. Case reports and series studies have reflected either consistent or variable and sometimes conflicting clinicopathologic findings. A few have reported electron microscopic findings. Immunohistochemistry is lacking. We report two multiple and four solitary forms of nevus lipomatosus in six patients, highlighting their salient histopathologic features and immunohistochemical profile. Both forms showed intradermal groups of perivascular S100+ lipogenic and CD34+ mesenchymal cells intermixed with scattered CD1a+ and FXIIIa+ dendrocytes, CD3 lymphocytic and CD117 mast cells in a fibromyxoid milieu. Epidermal nevoid and comedonal follicular alterations, attenuated dermal connective tissue and adnexal structures were variably present in both forms. We compared our findings with seven series of studies reporting classic and solitary forms. Both forms showed similar histopathologic findings, comparable clinicopathologic features, predominantly pelvic, and shoulder girdle distribution patterns in bimodal age onsets. Even though some lipomatous skin lesions clinically and histopathologically overlap with nevus lipomatosus, certain findings are helpful distinguishing features. Small intradermal islands of lipocytic fibroplasia have characteristic perivascular milieu that may function as a niche of preadipose CD34 mesenchymal stem cells. They are most likely represented in the dermis of the pelvic and shoulder areas in certain individuals prone to maintain these embryonic reservoirs, which are clinically manifested at different ages. Some may have unifocal or multifocal residues reflecting multiple and solitary forms.

Synovial Lipomatosis: Histopathologic Features in a Series of Five Cases.

Synovial lipomatosis is a controversial entity of uncommon intraarticular joint lesions. Most studies focused on radiological findings and surgical resection modalities. Pathologic findings were limited to case reports. Detailed descriptions of the histopathologic features are lacking. We aim to highlight the salient histopathologic features of synovial lipomatosis. We performed a retrospective review study over 15 years retrieving cases of synovial lipomatosis. We found 5 patients (age range: 8-78, average age: 50 years, male to female ratio: 4:1) demonstrating unilateral synovial lipomatosis out of 241 (2.0%) patients with knee joint lesions. Four patients had osteoarthritis. One patient was obese. The resected specimens showed synovial hyperplasia, surface fibrin, hemosiderin pigment, microcalcifications, lymphoplasmacytic infiltrates, lymphoid aggregates, stromal fibrotic, degenerative, and metaplastic alterations shared by other synovitis related changes. Consistent features included abundant adipocytic components, surface adipocytes, prominent large vessel vasculatures, plasma cells, and dense perivascular lymphocytic cuff-like infiltrates. One patient demonstrated superimposed sarcoid-type epithelioid granulomas. A distinct fibrous band separated the lesional tissue from the underlying normal fatty tissue. Synovial lipomatosis predominates in older males with degenerative joint conditions with a second peak in children and adolescents. Obesity is not a risk factor. Some histopathologic features help distinguish synovial lipomatosis from look-alike joint lesions. The findings may suggest an angiolipomatous hamartomatous growth or an exaggerated synovial reaction inducing florid subsynovial stromal proliferative, metaplastic, and degenerative changes. Regardless of its etiopathogenesis, pathologists have a role in confirming the diagnosis and ensuring a complete arthroscopic synovectomy by assessing the presence of the fibrous septa.

Brunner gland inflammation in Crohn's disease and Celiac disease: Overlapping inflammatory patterns suggest a possible link.

Similar to celiac disease, inflammatory bowel disease frequently manifests in the duodenum. Histopathologic studies focused on mucosal alterations with little attention to submucosal Brunner glands. Recently, several studies have demonstrated overlapping features between Crohn's disease and celiac disease suggesting a putative link. However, histopathologic studies evaluating this possible link are limited, and those that are focused on Brunner glands are lacking. The present study aims to explore whether Crohn's disease and celiac disease display shared or overlapping inflammatory changes in Brunner glands. We performed a retrospective review study over 17-years retrieving duodenal biopsy specimens containing Brunner gland lobules in patients with Crohn's disease, celiac disease, and ulcerative colitis. We found 10 out of 126 duodenal biopsies (8 %) in patients with Crohn's disease and 6 out of 134 (4.5 %) duodenal biopsies in patients with celiac disease sharing inflammatory patterns in duodenal Brunner gland lobules. Both diseases showed interstitial intralobular and interlobular mixed chronic inflammation with variable fibrosis. Focally enhanced active inflammation of Brunner gland lobules was more characteristic of Crohn's disease. Intralobular epithelioid granulomas and multinucleated giant cells were specific to Crohn's disease. Ulcerative colitis patients did not show similar features. The interstitial focally enhanced chronic inflammatory pattern was significantly (p < 0.05) associated with both diseases, while the other inflammatory patterns were not (p > 0.05). This overlapping inflammatory pattern in Brunner glands in patients with Crohn's disease and celiac disease is supportive of the previously reported link between the two diseases. Pathologists should pay more attention to Brunner glands when evaluating duodenal biopsies. Further studies are warranted to validate these observations and their relevance in the pathogenesis of autoinflammatory gastrointestinal diseases.

Foreign Bodies in Sinonasal Tissues: A Potential Pitfall yet a Hint to Oroantral Fistulas.

Foreign bodies in the maxillary sinus are infrequent findings with various organic and inorganic materials have been reported. Most are iatrogenic due to abnormal communications between the oral cavity and the sinus cavity, predominantly secondary to dental and oral procedures. Oroantral fistulas might be asymptomatic incidental findings or may present with sinusitis-related symptoms. Even though oroantral fistulas are frequently encountered iatrogenic complications, most studies focused on radiologic findings and surgical closure procedures. A few cases reported the histopathologic findings of foreign body-related antral sinusitis. Our aim is to report three cases of chronic maxillary sinusitis induced by various foreign bodies of oral and dental origin associated with oroantral fistulas. Our focus is to highlight the different histopathologic patterns, potential pitfalls and helpful clues of foreign body-induced maxillary sinusitis. Altered foreign bodies in procured sinus specimens might be missed, misinterpreted or ignored by pathologists. Obvious vegetable food remnants were detected, but subtle vegetable residuals showed pulse granuloma, rings and sheet-like patterns embedded in the granulation tissue and fibrous stroma. Some materials mimicked fungal hyphae while others were ignored as nonspecific debris. Periodic acid Schiff stain and polarizing light helped delineate their nature. Other helpful hints included the presence of oral-type squamous epithelium, crystals, hemosiderin pigments, dental materials such as alvogyl, and microorganisms of oral origin for example Actinomyces. Our series emphasizes the importance of correct recognition of foreign bodies of oral and dental origin in paranasal specimens to guide clinicians to the possibility of oroantral fistula-associated odontogenic sinusitis versus conventional rhinosinusitis.

Histopathologic Findings of Button Battery-Related Changes in a Perforated Meckel's Diverticulum: Report of Three Cases.

Background: A button battery can cause perforation of Meckel's diverticulum if sequestered in this blind ending bowel segment. Reported cases focused on clinical manifestations, management options, radiologic and intraoperative findings. We highlight the histopathologic features in perforated Meckel's diverticula due to ingested button batteries. Case report: Three toddlers presented with perforated Meckel's diverticula after button battery ingestion. Histologic examination of the diverticula showed multiple burn-like mucosal ulcerations and liquefactive wall perforations of the tips, associated with prominent siderotic pigment deposits and calcifications. There were various residual materials with variable staining patterns in the luminal debris, necrotic tissue and adjacent to submucosal blood vessels. Conclusion: There is accelerated deposition of iron and calcium associated with button batteries.

Acute monoblastic myeloid leukemic pleural effusion: Pitfalls and clues.

Acute myeloid leukemic pleural effusions are uncommon with heterogenous cytomorphology and variable immunoprofiles. This imposes a difficult cytologic diagnosis. In particular, acute myeloid leukemia of monocyte lineage mimicking benign and malignant lymphoid and non-lymphoid lesions is challenging. Few cases of acute myeloid monocyte-lineage leukemia have been reported. Our aim is to report a case of a 54-year-old female patient who presented with pancytopenia and bilateral pleural effusions. We highlight the characteristic cytomorphologic features, diagnostic pitfalls and helpful hints of acute monoblastic leukemia. Initially, the cells were misinterpreted as chronic inflammatory histiocytic infiltrates with reactive mesothelial cells. The presence of frequent mitotic figures, apoptotic bodies and a two-cell population raised the possibility of neoplastic cells. The cellular infiltrate simulated lymphoma, carcinoma and melanoma tumor cells. Cellblock immunocytochemistry however showed negative B-cell, T-cell, myeloid, Langerhans cell, plasma cell and dendritic cell lineage markers. They were positive for LCA, CD68, CD4 and CD117 with a high Ki67 index. The cytologically suggested impression of acute myeloid leukemia of monocyte origin favoring monoblastic variant was confirmed by flow cytometry and bone marrow trephine biopsy. Cytomorphologic clues included agranular amphophilic cytoplasm, occasional grooved indented nuclei, tingible body macrophages, associated plasma cells and absent granulocytes. The cytologic and cellblock findings matched the bone marrow trephine biopsy features. Cytopathologists should be aware of this unusual and challenging cytologic diagnosis in patients with pancytopenia and utilize at least two monocyte markers when formulating their differential diagnosis. Certain cytomorphologic features are helpful hints for their correct recognition.

Extranodal Mesenteric Follicular Dendritic Cell Sarcoma Expressing Keratin Antigens: What Pitfalls Initiate Diagnostic Clues.

Extranodal follicular dendritic cell sarcomas are infrequent diagnostically challenging tumors. Because of their rarity, heterogeneous histomorphologic features and variable histologic grades a significant number of extranodal lesions are prone to be misdiagnosed. Even though they have a characteristic immunoprofile, expression of a range of nonspecific markers is well documented. Even though they are typically negative for keratins, few authors have reported lesions expressing keratin. Keratin expressing tumors are more likely to be misinterpreted by pathologists further deterring their inclusion in the differential diagnosis. We report an intraabdominal mesenteric follicular dendritic cell sarcoma in a 44-year-old male that immunophenotypically expressed keratin antigens. The lesion showed a high-grade pleomorphic epithelioid appearance and the initial differential diagnosis included lymphoma, sarcomas, melanoma, and carcinomas. Follicular dendritic cell sarcoma was not considered. Expression of epithelial membrane antigen and keratin further deterred the diagnosis which was reached only after extensive use of immunomarkers. The tumor cells expressed CD21, CD23, and D2-40. Morphologically, the tumor showed some thymoma-like features with occasional TDT-expressing background T-lymphocytes. These features were hints to reconsider our differential diagnosis to include follicular dendritic cell tumors. Awareness of this aberrant staining of epithelial immunomarkers and attention to certain clues should encourage pathologists to consider this entity. Speculative assumptions may explain this unusual keratin expression in some lesions. The histomorphologic and immunohistochemical heterogeneity may suggest different variants and grades of follicular dendritic cell sarcomas. The prevalence, importance, and histogenesis of keratin expression in follicular dendritic cell sarcomas warrant further studies.

Cytologic manifestations of Hodgkin lymphoma in serous effusions.

Serous effusions occur in a small group of patients with classic Hodgkin lymphoma (cHL). Most effusions are benign inflammatory fluids. Malignant effusions predominantly in patients with treated relapsed diseases or rarely as a primary manifestation are diagnostically challenging to cytopathologists. Established cases of cHL with effusions were retrieved. Cytology slides were screened looking for Reed-Sternberg-Hodgkin (RSH) cells and patterns of background inflammatory cells. Cellblocks and their corresponding immunocytochemistry (ICC) slides were examined. The cytologic findings were correlated with nodal biopsy histopathologic and immunohistochemical features. We found six cases of benign and malignant pleural and pericardial effusions in patients with mediastinal nodular sclerosis-type cHL. Various cytomorphologic patterns were observed. Slides revealed sparsely scattered either isolated or aggregated mononuclear, binucleated and multinucleated RSH-like cells. Some may have been either disregarded as reactive mesothelial or histiocytic cells, or confused with other RSH-like malignant cells. The background varied between characteristic mixed inflammatory milieu, predominantly small lymphocytic or lymphohistiocytic with or without reactive mesothelial cells. Cytologic examination showed three positive cases (two cases with RSH cells confirmed by cellblock section ICC, one case with a mixed inflammatory infiltrate), and three benign effusions (one case with atypical RSH-like reactive mesothelial cells confirmed by ICC). Effusions associated with cHL exhibit different cytologic patterns. A high level of vigilance with utility of ICC has an important role in suspecting primary cases and confirming recurrences in known cases. The various cytologic patterns of cHL-associated benign and malignant effusions might reflect parallel pathophysiologic mechanisms.

Unusual Presentations of Mycobacterium Tuberculosis in HIV-Positive Patients: A Case Series.

Necrotizing and non-necrotizing epithelioid granulomatous chronic inflammation is the usual recognizable histopathologic presentation of mycobacterial infections. In immunosuppressed patients, atypical histomorphologic patterns may occur. Rare and diagnostically challenging manifestations of nontubercular mycobacterial infections in transplant and Human Immunodeficiency Virus (HIV)-infected patients include mycobacterial spindle cell pseudotumor and suppurative lesions. Lesions composed of nodular spindle cell proliferation mimicking inflammatory, histiocytoid and spindle cell tumors, and similarly suppurative lesions simulating abscesses have been mostly reported in association with nontuberculous mycobacterial infections mainly in nodal and various extranodal sites. Similar lesions related to Mycobacterium tuberculosis that involve serosal membranes are unusual and diagnostically challenging. Our aim is to report mycobacterial spindle cell pseudotumor-associated pericarditis, suppurative abscess-forming pleuritis, and cholesterol pleuritis due to tuberculosis in three HIV-infected young adult males. Initially, we confused the mycobacterial spindle cell pseudotumor for Kaposi sarcoma, the suppurative pleuritis for bacterial and fungal empyema, and the cholesterol pleuritis with rheumatoid arthritis. A prior knowledge of the immune status of our patients helped us confirm our final correct diagnosis of mycobacterial infection by performing Ziehl-Neelsen special stain. Polymerase chain reaction detected Mycobacterium tuberculosis in respiratory samples. Utilization of acid-fast special stains in all HIV-patients regardless of the histopathologic appearances, and the application of an appropriate panel of immunomarkers should help pathologists reach the correct diagnosis and avoid pitfalls. Without prior clinical knowledge, pathologists should raise this possibility in young patients with such unusual manifestations, because correct pathologic recognition is clinically important for the appropriate management of these vulnerable patients.

Quantum Mechanics and Surgical Pathology: A Brief Introduction.

Quantum mechanics (QM) and surgical pathology might seem totally unrelated fields of science. Because QM or particle physics explains the very basic structure and function of nature, there are growing interconnections between the fundamentals and applications of QM and biologic sciences. QM is not only applied to the structure of atoms but also probes the structure of biologic molecules, explains their mutational changes and has provided an insight into the basic mechanisms of many different biologic systems. Many of the current applications in biologic sciences, medicine, and surgical pathology rely on the principles of QM. Because surgical pathology uses quantum phenomena such as light and studies disease's alterations that are ultimately governed by quantum changes at nanoscale levels, QM will have potential future implications for the progress of surgical pathology. These might include quantum-enhanced refinements in light, ancillary tools, and interpretation assistance computerized systems. The future of applying the concepts, discoveries, and tools of QM in surgical pathology might create something analogous to quantum biology; that is, quantum pathology or "QuPath."