Diagnostica istologica della necrosi da bifosfonati: cosa il patologo può e deve dire
E. Maiorano
Dipartimento dell’Emergenza e dei Trapianti d’Organo (DETO) Uni- versità degli Studi di Bari Aldo Moro – Bari
Jawbones alterations that are electively related to biphospho- nates (BPs) therapy have been repeatedly reported over the last few years, due to increased administration, both parenter- ally and intra-orally, of different biphosphonate molecules in oncologic and osteoporotic patients. Though many of such lesions could be prevented by adequate intra-oral treatments before the start of therapies, prompt recognition of early le- sions is mandatory to avoid massive bone destruction and to possibly adopt minimally invasive surgical treatments. Recent studies have highligthed that biphosphonates reduce osteoclastic activity and bone resorption, and favour woven bone deposition, thus recovering bone losses due to osteopo- rosis and limiting bone invasion due to metastatic deposits. Nevertheless, such mechanisms of action also lead to the expansion of previously existing lamellar bone and accumu- lation of newly formed woven bone, thus inducing relative ischaemic conditions due to inadequate blood supply in in- volved areas. Therefore, bone lamellae progressively develop necrotic foci that are more prone to subsequent infection and inflammation. The latter are favoured by concomitant mas- ticatory trauma, endodontic treatments and dental implant procedures which should be avoided in patients after the start of biphosphonates therapies.
Morphologically, the salient features of BP-related osteone- crosis of the jaws include enlargement of pre-existing lamellar bone, progressive reduction of Haversian canals, irregular de- position of woven (newly-formed) bone, extensive polymor- phic (neutrophils, lymphocytes and plasma cells) acute and chronic inflammatory changes and accumulation of bacterial colonies. Opportunistic superinfection is rather frequent and is mainly sustained by Actinomyces species which deserve proper identification by PAS stains in view of specific antibi- otic treatment, to be started as soon as possible. Also, patients harbouring long-standing and extensive necrotic foci may undergo additional superinfection by uncommon pathogens, such as Mucormycetes and Aspergilli that may be sparse and quite hard to identify in H&E stained slides, thus prompting for additional special stains (Giemsa, Grocott Silver Methe- namine) to be performed. Proper identification of such patho- gens is mandatory to promptly start specific treatments and avoid possible lethal complications, frequently due to massive extension of the infection to the paranasal sinuses and brain. In conclusion, pathologists must be aware of the many subtle alterations that may be found in the jawbones of patients under- going BP therapy to support clinicians in the choice of adequate treatments, which may include selective and high-dose antibi- otic therapy in case resistant pathogens would be identified.
anomalie vascolari nel distretto testa-collo: criteri diagnostici
L. Moneghini1, M. Falleni1, C. E. Brambilla1, G. Colletti2,
G. Vercellio3, F. Melchiorre4, G. Bulfamante1
1Unit of Human Pathology, Department of Health Sciences, San Paolo
Hospital Medical School, University of Milano, Milano, Italy.
2Maxillo-facial Surgery Department, Department of Health Sciences,
San Paolo Hospital Medical School, University of Milano, Milano, Italy.
3Vascular Surgeon-Private Practice, Milan, Italy.
4Consultant, Department of Radiology, University of Milan, San Pao-
lo Hospital, Milan, Italy
Vascular anomalies form a heterogeneous group of pathologies of the circulatory system that can affect every type of hematic and /or lymphatic vessel of any diameter or anatomic area. The global incidence of vascular anomalies in the population is not known, but the incidence of vascular tumors is esti- mated between 6-8% and the one of vascular malformations about 1.5%.
The extreme variability of the type of tissue or organ involved may determine a wide heterogeneity of clinical conditions resulting in the need of different professionals and the need to undertake different diagnostic and therapeutic approaches. In addition, vascular abnormalities can be an expression of complex syndromes or malformations rare events; in these cases the clinical approach, diagnosis and treatment, which is already by definition multidisciplinary, will require more specific evaluations.
Precisely for these features vascular anomalies are lesions that require
- uniform classification criteria
- identification of specific diagnostic protocols in order to optimize the use of instrumental tests
- evaluation of different treatment methodologies in order to use the best therapeutic strategy in the various cases. Specifically, head and neck is a district where the vascular anomalies are the most common benign lesion in infancy and childhood and are reported in 14-65% of cases of all vascular anomalies. The correct diagnosis is critical to provide the ap- propriate treatment because it is an area of particular sensitiv- ity for the organs involved, both from the functional point of view as well as from that of social relations.
The authors reviewed the current literature on vascular anom- alies looking for more innovative and credited diagnostic criteria and treatment protocols.
Referring to what is currently achieved by SISAV(Società Italiana per lo Studio delle Anomalie Vascolari) the adopted classification to diagnose vascular abnormalities was the ISSVA Classification (2014) that has its roots in the previous classification of Mulliken and Glowacky (1982) 1. This clas-
sification is very simple and schematic. It distinguishes the vascular anomalies in two main groups: vascular tumors and vascular malformations. Furthermore, vascular malformations are distinct in relation to the hemodynamic characteristics in two main subtypes (fast flow and slow flow).
Treatment protocols suggested after a full review of the literature and according to the experience of the authors were applied. These protocols have been translated into national guidelines 2.
Even for the head and neck there is a multidisciplinary ap- proach involving radiologists, maxillo-facial surgeons, plastic surgeons and pathologists as well as professionals such as speech therapists and unusual make-up artists.The review is divided in 2 principal sections: tumor and malformation and the last one in additional 4 sections (capillary, venous, arteriovenous, and lym- phatic malformations). In each section, the clinical presentation, radiologic features, histological aspect and treatment options for each kind of vascular anomalies are described.
References
1 Mulliken JB, Glowacky J. Hemangiomas and vascular malformations in infant and children: a classification based on endothelial charac- teristics. Plast Reconstr sug 1982;69:412-22.
2 SISAV. Italian guideline for vascular anomalies. International Angi-
eventi indesiderati in anatomia patologica
G. Santeusanio1, R. Giardini2, E. De Dominicis3
1Dipartimento di Medicina Sperimentale e Chirurgia, Università de-
gli Studi di Roma “Tor Vergata”, UOC Anatomia e Istologia Patolo- gica, Ospedale S. Eugenio, Roma
2IRCCS Istituto Auxologico Italiano, Milano
3Medicina Legale, Dipartimento di Medicina Sperimentale e Chirur-
gia Università di Roma “Tor Vergata”, Roma
The discussion on adverse events in anatomic pathology gen- erally focuses on diagnostic error which involves problems related to diagnostic criteria, diagnostic threshold, compe- tency, inadequate clinical correlation, and experience. Unfor- tunately, there is a small number of adverse events that occur at a very low rate and their impact on a patient’s care may be dramatic, such as “misidentification of a patient or a speci- men”, “floaters” (or extraneous tissues, or contaminants), and the “loss of surgical specimens”.
Misidentification of a patient or a specimen.
One of the most serious issues faced in Anatomic Pathology services is misidentification of a patient or a specimen, which in- cludes mislabeled specimens, block identification problems, and tissue contaminants with the potential to cause patients harm 1.
The terms ‘‘patient identification error’’, ‘‘specimen identifi- cation error’’, ‘‘laboratory identification error “, and simply ‘‘identification error’’are used interchangeably. Any result that is reported for the wrong patient or specimen is consid- ered an identification error. A mix-up of two specimens from the same patient collected from different sites is still consid- ered an identification error, because the site can be important in interpreting results and planning subsequent care. Patho- logical examination of a surgical specimen is the mid-point of a complex, multi-step process, that begins with receipt of a labeled specimen and requisition, followed by accessioning of that specimen into the laboratory with assignment of an alphanumeric accession designation unique to that patient and case, and examination of the specimen with submission of tis- sue samples into labeled tissue cassettes, which are processed into paraffin blocks and subsequently cut to produce tissue sections adhered to labeled glass slides which are microscopi- cally examined by the pathologist. The system in surgical pathology has little or no automation and is heavily dependent on numerous people with varying levels of training. In fact, the handling, processing and reporting of pathology speci- mens involves many members of the health-care team includ- ing physicians, nurses, pathologist, laboratory technologists and administrative personnel. Therefore, the system has a high potential for error. Identification errors can occur at any point in the process and involve a patient or a specimen. In a patient identification error (where the cause of the identification error was misidentification of the patient, i.e. a defective or missing patient identification number on cassette or paraffin block), a specimen is labeled with the incorrect patient name or identi- fication number. In a specimen identification error (where the patient was correctly identified, but the specimen was not), a specimen is misidentified as to organ or site of origin, but the
specimen is correctly associated with patient name and iden- tification number. Either error has the potential to cause pa- tients harm such as inappropriate therapy or follow-up, wrong side treatment, withholding of therapy in patients with unrec- ognized malignancies, repeat diagnostic procedure, including tissue biopsy and delay in a necessary surgical procedure. In an anatomic pathology laboratory labeling errors for patient or sample can occur at several points in specimen processing involving case/patient (wrong accession number was applied to the entire case), specimen (wrong specimen labeling was due to mix-up of specimens within a case, e.g. right versus left specimens in a bilateral biopsy from the same patient), paraf- fin block (histologic block was labeled with the wrong patient/ case identification or wrong sequence number or letter), and slide (histologic slide was labeled with the wrong specimen / patient identification, sequence number, or letter) 2-5. Pa-
tient identification errors in surgical pathology are the most rapidly growing category of malpractice claims involving pathologists. In a study of medical malpractice cases against pathologists, Troxel 6 describes four claims that resulted from
misidentified pathology reports, blocks, or specimens leading to patients being told they had malignancies when they actu- ally did not attributable to patient misidentifications at some point in the surgical pathology process, and in a follow-up study, 7 he noted a sharp increase in histology errors, with 13
of 272 claims attributable to specimen mix-ups and 2 of 272 to mislabeled slides. In a study of 227 root cause analyses Dunn and Moga 8 identified 8 cases in which mislabeling of
anatomic pathology specimens, slides, or tissue cassettes led to significant patient harm, including unnecessary surgery (lung lobectomy, prostatectomy, hysterectomy), delays in diagnosis, and necessity for repeat procedures.
Few studies have addressed the frequency of labeling errors for anatomic pathology specimens. In a College of American Pathologists Q-Probes program, specimen identification and accessioning deficiencies were found in 60,042 of 1,004,115 cases accessioned (6.0%) 3. Errors associated with specimen
misidentification accounted for 9.6% of the total errors 3. La-
beling errors have been categorized as class 1 (typographical errors with no clinical consequences); class 2 (minor errors unlikely to have clinical consequences); and class 3 (errors that are significant and have the potential to detrimentally impact patient care).
In another study, Francis et al. 9 documented the frequency
of preanalytic errors in a high-volume endoscopy center. In a study of 8,231 specimen containers, they documented a 0.09% rate for class 3 errors in which specimen bottles were mislabeled for patient name or unique identification number. Makary et al. 4 reviewed a total of 21,351 surgical specimens
and detected 91 errors in specimen labeling. Of these errors, 11 (12%) involved specimens associated with an incorrect pa- tient assignment, and specimens most commonly mislabeled were breast, skin, and colon.
Specimen labeling errors within the laboratory can occur at several points of specimen processing. Within the gross room, specimen containers can be paired with cassettes labeled Aula Gialla 1 – 9.30-12.30